Melissa R. Arbuckle, MD: Hi. I’m Dr. Melissa Arbuckle, vice chair for education and training in the Department of Psychiatry at Columbia University. I’m reporting on behalf of Medscape and our Columbia Psychiatry partnership. Today we’ll be discussing biomarkers with Dr. Jeffrey Lieberman. Welcome.

Jeffrey A. Lieberman, MD: Thanks, Melissa. Great to be here to talk about a subject that is near and dear to my heart.



Dr. Arbuckle: Dr. Lieberman is chair of the Department of Psychiatry at Columbia and is also director of the New York State Psychiatric Institute. Tell us about biomarkers and psychiatry, Dr Lieberman.

Dr. Lieberman: It would be nice if we had some! But first let me tell you what a biomarker is and what it would do for us. A biomarker is a biologic measure, a biologic feature, whether it’s blood pressure, pulse rate, an analyte in blood or cerebrospinal fluid, or a feature of an MRI or PET scan image of the brain that has diagnostic, prognostic, or theragnostic significance. A biomarker identifies an individual with symptoms of a specific disorder, indicates that they have this disorder, and can suggest a particular prognosis – less severe, more severe – or specify which treatment a person would likely respond to. For the entire history of our discipline, as long as physicians have studied mental illness, we have not had a diagnostic test for it. It’s a clinical diagnosis.

All illnesses in medicine began with clinical diagnosis: seizure disorder, epilepsy, was falling sickness; congestive heart failure was dropsy; for diabetes you tasted the urine to see if it was sweet or watery. But when we began to measure glucose and hemoglobin A1c, or when we developed the electrocardiogram to measure heart rhythms, and the electroencephalogram to measure brain activity, those were diagnostic tests based on biomarkers. We just don’t have them yet in psychiatry. The day we do have our first diagnostic tests, courtesy of a validated biomarker, will be a real milestone in the history of our profession.



Dr. Arbuckle: How far off might that be for psychiatry?

Dr. Lieberman: I’ve been in this profession for more than 30 years, and I’ve been saying for a while that it is coming soon. But we’re still waiting. Let me just add a cautionary note. Ever since psychiatry became scientifically minded and used scientific methodology and technology to understand the underpinnings of mental illness, there’s been an effort to identify biomarkers. It began in the 1960s with a series of false leads. There was something called the pink spot, as well as other metabolites, which were indicators on chromatographs linked to schizophrenia. This turned out to be wrong.

There was also the dexamethasone suppression test, to identify people who hypersecreted cortisol, which was believed to be diagnostic of depression. That turned out to be inadequate also.

There was the identification of genes beginning in the late 1980s. But the specific genes that indicated manic depressive illness and schizophrenia were not replicated. And now we know that the genetics of these disorders is polygenic and very complex.

So we cannot overpromise. I don’t want to say exactly when, but I will say that this is an area of intense research. There are a variety of different technologies that could yield this holy grail of diagnostic measures, including imaging measures such as MRI, PET, and nuclear medicine imaging, the use of genetics to create a polygenic risk score, and serologic analyses of blood to develop a panel of measures that may predict a specific condition or specific subtype of a condition.

It’s very likely, though, that we’ll not have a single pathognomonic test. I suspect that we’ll have several measures that, in combination, will be diagnostic or prognostic, in the same way that with cancer you have nomograms that give a prognosis. Or in the case of cardiovascular disease, where you have a lipid panel that takes into account a variety of lipid analytes to give you a risk score. I do believe that certainly within my professional lifetime, and hopefully sooner rather than later, we will see a diagnostic test.



Dr. Arbuckle: Given the different tests that did not pan out, what guidance can we offer clinicians as data come out and new potential biomarkers hit the media? How can we sift through what may or may not hold real promise?

Dr. Lieberman: I can tell practicing clinicians what not to do. Do not do what some of the charlatans in our field do. There are self-promoting psychiatrists out there who use SPECT scans to get a picture of the brain that is little more than pseudo color phrenology, and then they tell patients, “See this? This indicates that you have (this condition or that condition).” You can’t do that. Nothing we have now has that kind of validity or specificity.

However, even though a standard workup for an illness like schizophrenia does not require specific diagnostic tests, other than to rule out other conditions, imaging procedures can be useful additional information. For example, if you have an individual who presents with symptoms that meet criteria for schizophrenia and you obtain an MRI to rule out other possibilities, and the patient turns out to have dilated lateral ventricles or specific reductions in the size or distortions in the shape of certain temporal cortical structures, particularly in the hippocampus, that adds substance to your clinical diagnosis. So those kinds of things are useful. Similarly, with genetic testing, some institutions are now doing exome sequencing or whole genome sequencing that can provide a risk score. It adds something beyond a family history. These are not diagnostic, but they can add to your understanding.

Finally, with respect to schizophrenia and MRI in particular, if it does show structural abnormalities that are among the ones that have been reported for schizophrenia, this can be informative prognostically; such an individual may have a greater likelihood of having a chronic course with progression of the illness. And if that were my patient, I would be thinking that greater effort needs to be taken to ensure that the patient remains on treatment and does not suffer relapse.



Dr. Arbuckle: How do we prepare our trainees for a future of psychiatry with more biomarkers?

Dr. Lieberman: In medical school and postgraduate training, apart from understanding the method of diagnosis and the criteria for diagnoses, it’s important to understand the ancillary measures that are used in clinical medicine: blood testing, electrophysiologic measures, imaging procedures, neurocognitive testing, etc. This is a standard in terms of general medical training.

In terms of then applying it to mental illness and psychiatry, it’s a matter of knowing that these will be relevant at some point, staying apprised of the research literature that is generating data that pertain to the use of these measures for diagnostic, prognostic, or treatment-specific purposes, and then gauging how useful these will be. Right now, these measures are not required for diagnosis. They’re not validated sufficiently so that third-party payers will uniformly reimburse for them, but at some point they will be. Even before that time occurs, there are some measures that can be informative and enhance confidence in the diagnosis or add information about treatment response and outcome.



Dr. Arbuckle: We’re hearing about biotypes and how biotypes may not map to our current diagnostic systems. What are your thoughts about that?

Dr. Lieberman: You know, psychiatry has always been kind of the stepchild of medicine. And related to that, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the punching bag of the critics of psychiatry and the purported reason it hasn’t progressed faster. Sitting here at Columbia, the home of Robert Spitzer, who was the pioneer of the modern method of nosology that we still use in the DSM, it’s disappointing that we continue to lob tomatoes at this system, which is the best. It took psychiatry out of what was a dark age of clinical methodology and put it on solid scientific footing. That was in the late 1970s with [the development of] DSM-III.

And as much as we would like to have further progress, which would allow for not using a list of criteria in a menu-driven fashion to establish diagnoses, we’d like to have it be like a glucose tolerance test or an angiogram.

We’d like to do that, but we can’t yet. So there’s this aspirational desire to have something better, and this is permeating and motivating a lot of the research, which is good. But to claim that these don’t map to the current DSM and therefore invalidate the DSM-defined diagnoses is wrong and self-defeating. If the biotypes were validated, we would be using them. So if they don’t map to the current DSM diagnosis, is the diagnosis wrong or are the biotypes wrong? I believe it’s wishful thinking; individuals are trying to project their desires onto clinical practice, and it’s not desirable to do that. If there was anything that was an improvement on the DSM, it would have been incorporated into our practice.

The question about the limitations of DSM and the improved methods of neuroscientifically informed diagnostic systems was an issue that brought me into a confrontation with our former director of the National Institute of Mental Health (NIMH) in 2013.

After 5 years of the DSM task force laboring to revise the fifth edition of the DSM, as it was about to be launched, our former director, Tom Insel, disavowed it and proposed as a preferable alternative the research domains criteria (RDoC) system that was in development at the NIMH, which I believe epitomized this kind of sour grapes at what psychiatry didn’t have – an aspiration to have a more neuroscientifically informed diagnostic system. And as soon as he made the statement publicly, he had to walk it back because the RDoC system or any other system was not ready for prime time. It would have been a catastrophe if it would have been the one that informed clinical psychiatry. There was nothing that was superior to the DSM to be used at the time. This shows how frustration sometimes impels people to make rash statements.

We’re on the right track. Our field is progressing enormously, and one has to remember that everything that’s relevant in terms of being scientifically based and validated through empirical research in clinical psychiatry and mental illness has happened since the last half of the 20th century.

It is a very short period of time. We’ve made tremendous progress, and we’re continuing to make progress toward the milestone we’re all hoping for, where we have diagnostic tests. But we shouldn’t shortchange ourselves or underestimate the progress we have made in the meantime.
 

Dr. Arbuckle: This has been a great conversation. Signing off for Medscape and Columbia Psychiatry. Thank you.

Dr. Lieberman is chairman of the Department of Psychiatry at Columbia University. He is a former president of the American Psychiatric Association. Dr. Arbuckle is vice chair for education and director of resident education in the Department of Psychiatry at Columbia University. She is particularly interested in the role of medical education in translating research into the practice of psychiatry.

This article first appeared on Medscape.com.

Melissa R. Arbuckle, MD: Hi. I’m Dr. Melissa Arbuckle, vice chair for education and training in the Department of Psychiatry at Columbia University. I’m reporting on behalf of Medscape and our Columbia Psychiatry partnership. Today we’ll be discussing biomarkers with Dr. Jeffrey Lieberman. Welcome.

Jeffrey A. Lieberman, MD: Thanks, Melissa. Great to be here to talk about a subject that is near and dear to my heart.



Dr. Arbuckle: Dr. Lieberman is chair of the Department of Psychiatry at Columbia and is also director of the New York State Psychiatric Institute. Tell us about biomarkers and psychiatry, Dr Lieberman.

Dr. Lieberman: It would be nice if we had some! But first let me tell you what a biomarker is and what it would do for us. A biomarker is a biologic measure, a biologic feature, whether it’s blood pressure, pulse rate, an analyte in blood or cerebrospinal fluid, or a feature of an MRI or PET scan image of the brain that has diagnostic, prognostic, or theragnostic significance. A biomarker identifies an individual with symptoms of a specific disorder, indicates that they have this disorder, and can suggest a particular prognosis – less severe, more severe – or specify which treatment a person would likely respond to. For the entire history of our discipline, as long as physicians have studied mental illness, we have not had a diagnostic test for it. It’s a clinical diagnosis.

All illnesses in medicine began with clinical diagnosis: seizure disorder, epilepsy, was falling sickness; congestive heart failure was dropsy; for diabetes you tasted the urine to see if it was sweet or watery. But when we began to measure glucose and hemoglobin A1c, or when we developed the electrocardiogram to measure heart rhythms, and the electroencephalogram to measure brain activity, those were diagnostic tests based on biomarkers. We just don’t have them yet in psychiatry. The day we do have our first diagnostic tests, courtesy of a validated biomarker, will be a real milestone in the history of our profession.



Dr. Arbuckle: How far off might that be for psychiatry?

Dr. Lieberman: I’ve been in this profession for more than 30 years, and I’ve been saying for a while that it is coming soon. But we’re still waiting. Let me just add a cautionary note. Ever since psychiatry became scientifically minded and used scientific methodology and technology to understand the underpinnings of mental illness, there’s been an effort to identify biomarkers. It began in the 1960s with a series of false leads. There was something called the pink spot, as well as other metabolites, which were indicators on chromatographs linked to schizophrenia. This turned out to be wrong.

There was also the dexamethasone suppression test, to identify people who hypersecreted cortisol, which was believed to be diagnostic of depression. That turned out to be inadequate also.

There was the identification of genes beginning in the late 1980s. But the specific genes that indicated manic depressive illness and schizophrenia were not replicated. And now we know that the genetics of these disorders is polygenic and very complex.

So we cannot overpromise. I don’t want to say exactly when, but I will say that this is an area of intense research. There are a variety of different technologies that could yield this holy grail of diagnostic measures, including imaging measures such as MRI, PET, and nuclear medicine imaging, the use of genetics to create a polygenic risk score, and serologic analyses of blood to develop a panel of measures that may predict a specific condition or specific subtype of a condition.

It’s very likely, though, that we’ll not have a single pathognomonic test. I suspect that we’ll have several measures that, in combination, will be diagnostic or prognostic, in the same way that with cancer you have nomograms that give a prognosis. Or in the case of cardiovascular disease, where you have a lipid panel that takes into account a variety of lipid analytes to give you a risk score. I do believe that certainly within my professional lifetime, and hopefully sooner rather than later, we will see a diagnostic test.



Dr. Arbuckle: Given the different tests that did not pan out, what guidance can we offer clinicians as data come out and new potential biomarkers hit the media? How can we sift through what may or may not hold real promise?

Dr. Lieberman: I can tell practicing clinicians what not to do. Do not do what some of the charlatans in our field do. There are self-promoting psychiatrists out there who use SPECT scans to get a picture of the brain that is little more than pseudo color phrenology, and then they tell patients, “See this? This indicates that you have (this condition or that condition).” You can’t do that. Nothing we have now has that kind of validity or specificity.

However, even though a standard workup for an illness like schizophrenia does not require specific diagnostic tests, other than to rule out other conditions, imaging procedures can be useful additional information. For example, if you have an individual who presents with symptoms that meet criteria for schizophrenia and you obtain an MRI to rule out other possibilities, and the patient turns out to have dilated lateral ventricles or specific reductions in the size or distortions in the shape of certain temporal cortical structures, particularly in the hippocampus, that adds substance to your clinical diagnosis. So those kinds of things are useful. Similarly, with genetic testing, some institutions are now doing exome sequencing or whole genome sequencing that can provide a risk score. It adds something beyond a family history. These are not diagnostic, but they can add to your understanding.

Finally, with respect to schizophrenia and MRI in particular, if it does show structural abnormalities that are among the ones that have been reported for schizophrenia, this can be informative prognostically; such an individual may have a greater likelihood of having a chronic course with progression of the illness. And if that were my patient, I would be thinking that greater effort needs to be taken to ensure that the patient remains on treatment and does not suffer relapse.



Dr. Arbuckle: How do we prepare our trainees for a future of psychiatry with more biomarkers?

Dr. Lieberman: In medical school and postgraduate training, apart from understanding the method of diagnosis and the criteria for diagnoses, it’s important to understand the ancillary measures that are used in clinical medicine: blood testing, electrophysiologic measures, imaging procedures, neurocognitive testing, etc. This is a standard in terms of general medical training.

In terms of then applying it to mental illness and psychiatry, it’s a matter of knowing that these will be relevant at some point, staying apprised of the research literature that is generating data that pertain to the use of these measures for diagnostic, prognostic, or treatment-specific purposes, and then gauging how useful these will be. Right now, these measures are not required for diagnosis. They’re not validated sufficiently so that third-party payers will uniformly reimburse for them, but at some point they will be. Even before that time occurs, there are some measures that can be informative and enhance confidence in the diagnosis or add information about treatment response and outcome.



Dr. Arbuckle: We’re hearing about biotypes and how biotypes may not map to our current diagnostic systems. What are your thoughts about that?

Dr. Lieberman: You know, psychiatry has always been kind of the stepchild of medicine. And related to that, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the punching bag of the critics of psychiatry and the purported reason it hasn’t progressed faster. Sitting here at Columbia, the home of Robert Spitzer, who was the pioneer of the modern method of nosology that we still use in the DSM, it’s disappointing that we continue to lob tomatoes at this system, which is the best. It took psychiatry out of what was a dark age of clinical methodology and put it on solid scientific footing. That was in the late 1970s with [the development of] DSM-III.

And as much as we would like to have further progress, which would allow for not using a list of criteria in a menu-driven fashion to establish diagnoses, we’d like to have it be like a glucose tolerance test or an angiogram.

We’d like to do that, but we can’t yet. So there’s this aspirational desire to have something better, and this is permeating and motivating a lot of the research, which is good. But to claim that these don’t map to the current DSM and therefore invalidate the DSM-defined diagnoses is wrong and self-defeating. If the biotypes were validated, we would be using them. So if they don’t map to the current DSM diagnosis, is the diagnosis wrong or are the biotypes wrong? I believe it’s wishful thinking; individuals are trying to project their desires onto clinical practice, and it’s not desirable to do that. If there was anything that was an improvement on the DSM, it would have been incorporated into our practice.

The question about the limitations of DSM and the improved methods of neuroscientifically informed diagnostic systems was an issue that brought me into a confrontation with our former director of the National Institute of Mental Health (NIMH) in 2013.

After 5 years of the DSM task force laboring to revise the fifth edition of the DSM, as it was about to be launched, our former director, Tom Insel, disavowed it and proposed as a preferable alternative the research domains criteria (RDoC) system that was in development at the NIMH, which I believe epitomized this kind of sour grapes at what psychiatry didn’t have – an aspiration to have a more neuroscientifically informed diagnostic system. And as soon as he made the statement publicly, he had to walk it back because the RDoC system or any other system was not ready for prime time. It would have been a catastrophe if it would have been the one that informed clinical psychiatry. There was nothing that was superior to the DSM to be used at the time. This shows how frustration sometimes impels people to make rash statements.

We’re on the right track. Our field is progressing enormously, and one has to remember that everything that’s relevant in terms of being scientifically based and validated through empirical research in clinical psychiatry and mental illness has happened since the last half of the 20th century.

It is a very short period of time. We’ve made tremendous progress, and we’re continuing to make progress toward the milestone we’re all hoping for, where we have diagnostic tests. But we shouldn’t shortchange ourselves or underestimate the progress we have made in the meantime.
 

Dr. Arbuckle: This has been a great conversation. Signing off for Medscape and Columbia Psychiatry. Thank you.

Dr. Lieberman is chairman of the Department of Psychiatry at Columbia University. He is a former president of the American Psychiatric Association. Dr. Arbuckle is vice chair for education and director of resident education in the Department of Psychiatry at Columbia University. She is particularly interested in the role of medical education in translating research into the practice of psychiatry.

This article first appeared on Medscape.com.

Melissa R. Arbuckle, MD: Hi. I’m Dr. Melissa Arbuckle, vice chair for education and training in the Department of Psychiatry at Columbia University. I’m reporting on behalf of Medscape and our Columbia Psychiatry partnership. Today we’ll be discussing biomarkers with Dr. Jeffrey Lieberman. Welcome.

Jeffrey A. Lieberman, MD: Thanks, Melissa. Great to be here to talk about a subject that is near and dear to my heart.



Dr. Arbuckle: Dr. Lieberman is chair of the Department of Psychiatry at Columbia and is also director of the New York State Psychiatric Institute. Tell us about biomarkers and psychiatry, Dr Lieberman.

Dr. Lieberman: It would be nice if we had some! But first let me tell you what a biomarker is and what it would do for us. A biomarker is a biologic measure, a biologic feature, whether it’s blood pressure, pulse rate, an analyte in blood or cerebrospinal fluid, or a feature of an MRI or PET scan image of the brain that has diagnostic, prognostic, or theragnostic significance. A biomarker identifies an individual with symptoms of a specific disorder, indicates that they have this disorder, and can suggest a particular prognosis – less severe, more severe – or specify which treatment a person would likely respond to. For the entire history of our discipline, as long as physicians have studied mental illness, we have not had a diagnostic test for it. It’s a clinical diagnosis.

All illnesses in medicine began with clinical diagnosis: seizure disorder, epilepsy, was falling sickness; congestive heart failure was dropsy; for diabetes you tasted the urine to see if it was sweet or watery. But when we began to measure glucose and hemoglobin A1c, or when we developed the electrocardiogram to measure heart rhythms, and the electroencephalogram to measure brain activity, those were diagnostic tests based on biomarkers. We just don’t have them yet in psychiatry. The day we do have our first diagnostic tests, courtesy of a validated biomarker, will be a real milestone in the history of our profession.



Dr. Arbuckle: How far off might that be for psychiatry?

Dr. Lieberman: I’ve been in this profession for more than 30 years, and I’ve been saying for a while that it is coming soon. But we’re still waiting. Let me just add a cautionary note. Ever since psychiatry became scientifically minded and used scientific methodology and technology to understand the underpinnings of mental illness, there’s been an effort to identify biomarkers. It began in the 1960s with a series of false leads. There was something called the pink spot, as well as other metabolites, which were indicators on chromatographs linked to schizophrenia. This turned out to be wrong.

There was also the dexamethasone suppression test, to identify people who hypersecreted cortisol, which was believed to be diagnostic of depression. That turned out to be inadequate also.

There was the identification of genes beginning in the late 1980s. But the specific genes that indicated manic depressive illness and schizophrenia were not replicated. And now we know that the genetics of these disorders is polygenic and very complex.

So we cannot overpromise. I don’t want to say exactly when, but I will say that this is an area of intense research. There are a variety of different technologies that could yield this holy grail of diagnostic measures, including imaging measures such as MRI, PET, and nuclear medicine imaging, the use of genetics to create a polygenic risk score, and serologic analyses of blood to develop a panel of measures that may predict a specific condition or specific subtype of a condition.

It’s very likely, though, that we’ll not have a single pathognomonic test. I suspect that we’ll have several measures that, in combination, will be diagnostic or prognostic, in the same way that with cancer you have nomograms that give a prognosis. Or in the case of cardiovascular disease, where you have a lipid panel that takes into account a variety of lipid analytes to give you a risk score. I do believe that certainly within my professional lifetime, and hopefully sooner rather than later, we will see a diagnostic test.



Dr. Arbuckle: Given the different tests that did not pan out, what guidance can we offer clinicians as data come out and new potential biomarkers hit the media? How can we sift through what may or may not hold real promise?

Dr. Lieberman: I can tell practicing clinicians what not to do. Do not do what some of the charlatans in our field do. There are self-promoting psychiatrists out there who use SPECT scans to get a picture of the brain that is little more than pseudo color phrenology, and then they tell patients, “See this? This indicates that you have (this condition or that condition).” You can’t do that. Nothing we have now has that kind of validity or specificity.

However, even though a standard workup for an illness like schizophrenia does not require specific diagnostic tests, other than to rule out other conditions, imaging procedures can be useful additional information. For example, if you have an individual who presents with symptoms that meet criteria for schizophrenia and you obtain an MRI to rule out other possibilities, and the patient turns out to have dilated lateral ventricles or specific reductions in the size or distortions in the shape of certain temporal cortical structures, particularly in the hippocampus, that adds substance to your clinical diagnosis. So those kinds of things are useful. Similarly, with genetic testing, some institutions are now doing exome sequencing or whole genome sequencing that can provide a risk score. It adds something beyond a family history. These are not diagnostic, but they can add to your understanding.

Finally, with respect to schizophrenia and MRI in particular, if it does show structural abnormalities that are among the ones that have been reported for schizophrenia, this can be informative prognostically; such an individual may have a greater likelihood of having a chronic course with progression of the illness. And if that were my patient, I would be thinking that greater effort needs to be taken to ensure that the patient remains on treatment and does not suffer relapse.



Dr. Arbuckle: How do we prepare our trainees for a future of psychiatry with more biomarkers?

Dr. Lieberman: In medical school and postgraduate training, apart from understanding the method of diagnosis and the criteria for diagnoses, it’s important to understand the ancillary measures that are used in clinical medicine: blood testing, electrophysiologic measures, imaging procedures, neurocognitive testing, etc. This is a standard in terms of general medical training.

In terms of then applying it to mental illness and psychiatry, it’s a matter of knowing that these will be relevant at some point, staying apprised of the research literature that is generating data that pertain to the use of these measures for diagnostic, prognostic, or treatment-specific purposes, and then gauging how useful these will be. Right now, these measures are not required for diagnosis. They’re not validated sufficiently so that third-party payers will uniformly reimburse for them, but at some point they will be. Even before that time occurs, there are some measures that can be informative and enhance confidence in the diagnosis or add information about treatment response and outcome.



Dr. Arbuckle: We’re hearing about biotypes and how biotypes may not map to our current diagnostic systems. What are your thoughts about that?

Dr. Lieberman: You know, psychiatry has always been kind of the stepchild of medicine. And related to that, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the punching bag of the critics of psychiatry and the purported reason it hasn’t progressed faster. Sitting here at Columbia, the home of Robert Spitzer, who was the pioneer of the modern method of nosology that we still use in the DSM, it’s disappointing that we continue to lob tomatoes at this system, which is the best. It took psychiatry out of what was a dark age of clinical methodology and put it on solid scientific footing. That was in the late 1970s with [the development of] DSM-III.

And as much as we would like to have further progress, which would allow for not using a list of criteria in a menu-driven fashion to establish diagnoses, we’d like to have it be like a glucose tolerance test or an angiogram.

We’d like to do that, but we can’t yet. So there’s this aspirational desire to have something better, and this is permeating and motivating a lot of the research, which is good. But to claim that these don’t map to the current DSM and therefore invalidate the DSM-defined diagnoses is wrong and self-defeating. If the biotypes were validated, we would be using them. So if they don’t map to the current DSM diagnosis, is the diagnosis wrong or are the biotypes wrong? I believe it’s wishful thinking; individuals are trying to project their desires onto clinical practice, and it’s not desirable to do that. If there was anything that was an improvement on the DSM, it would have been incorporated into our practice.

The question about the limitations of DSM and the improved methods of neuroscientifically informed diagnostic systems was an issue that brought me into a confrontation with our former director of the National Institute of Mental Health (NIMH) in 2013.

After 5 years of the DSM task force laboring to revise the fifth edition of the DSM, as it was about to be launched, our former director, Tom Insel, disavowed it and proposed as a preferable alternative the research domains criteria (RDoC) system that was in development at the NIMH, which I believe epitomized this kind of sour grapes at what psychiatry didn’t have – an aspiration to have a more neuroscientifically informed diagnostic system. And as soon as he made the statement publicly, he had to walk it back because the RDoC system or any other system was not ready for prime time. It would have been a catastrophe if it would have been the one that informed clinical psychiatry. There was nothing that was superior to the DSM to be used at the time. This shows how frustration sometimes impels people to make rash statements.

We’re on the right track. Our field is progressing enormously, and one has to remember that everything that’s relevant in terms of being scientifically based and validated through empirical research in clinical psychiatry and mental illness has happened since the last half of the 20th century.

It is a very short period of time. We’ve made tremendous progress, and we’re continuing to make progress toward the milestone we’re all hoping for, where we have diagnostic tests. But we shouldn’t shortchange ourselves or underestimate the progress we have made in the meantime.
 

Dr. Arbuckle: This has been a great conversation. Signing off for Medscape and Columbia Psychiatry. Thank you.

Dr. Lieberman is chairman of the Department of Psychiatry at Columbia University. He is a former president of the American Psychiatric Association. Dr. Arbuckle is vice chair for education and director of resident education in the Department of Psychiatry at Columbia University. She is particularly interested in the role of medical education in translating research into the practice of psychiatry.

This article first appeared on Medscape.com.

As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.

Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”

The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”

The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”

From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.

The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.

There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.

Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.

The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.

If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.

On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.

“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.

“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”

Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”

One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.

Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.

“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”

SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.

As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.

Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”

The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”

The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”

From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.

The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.

There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.

Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.

The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.

If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.

On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.

“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.

“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”

Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”

One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.

Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.

“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”

SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.

As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.

Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”

The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”

The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”

From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.

The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.

There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.

Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.

The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.

If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.

On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.

“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.

“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”

Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”

One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.

Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.

“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”

SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.

The rapid increase in thyroid cancer incidence that has occurred since the 1990s – considered an “epidemic of overdiagnosis,” has extended beyond high-income countries to less affluent settings, where unnecessary – and sometimes opportunistic – screening could continue to thrive.

“The impact of overdiagnosis on the increasing incidence of thyroid cancer highlighted in our report is a warning sign for countries with growing economies, where diagnostic technologies are increasingly and routinely offered, usually in exchange for payment, despite evidence that the harms far outweigh benefits,” the authors say.

“Overdiagnosis could turn healthy people into patients, and expose them to unnecessary harms and lifelong treatments,” say Mengmeng Li, PhD, of the International Agency for Research on Cancer, Lyon, France, and colleagues in their article published in Lancet Diabetes & Endocrinology.

With their previous research showing high rates of overdiagnosis in high-income countries, for this new analysis, they sought to evaluate whether similar patterns were occurring in less affluent settings.

They examined data from population-based cancer registries in 26 countries on four continents, looking at all cases of thyroid cancer reported between 1998 and 2012 in men and women aged 15 to 84 years.
 

A global public health problem

The results showed that while the incidence of thyroid cancer steadily increased from 1998 to 2002 and from 2008 to 2012 in all high-income countries, similar trends were also seen in less affluent nations, particularly in Belarus, China, Colombia, and Lithuania.

The increases were consistently greater among middle-aged women aged 35-64 years in all countries.

To determine what proportion of the higher incidence was overdiagnosis, the authors turned to historic age-specific thyroid cancer incidence data prior to the introduction of ultrasound and then looked at the progressive departure from that pattern, likely the result of the increased detection by ultrasound of thyroid nodules in middle-aged adults.

The results showed the proportion of thyroid cancer cases in women estimated to be attributable to overdiagnosis between 2008 and 2012 was as much as 93% in South Korea, 91% in Belarus, 87% in China, 84% in Italy and Croatia, and 83% in Slovakia and France.

Proportions attributable to overdiagnosis were lower in Denmark (66%), Norway (65%), Ireland (63%), United Kingdom (58%), Japan (55%), and Thailand (44%).

Women were much more likely to be overdiagnosed than men, with an approximate ratio of 3:1 in all countries; however, mortality and prevalence of thyroid cancer in autopsies were similar between genders.

Although researchers only looked at data up until 2012, Dr. Li said that, even in that year, “the amplitude of the phenomenon” was “already large and is increasing rapidly over time.”

Figures for periods subsequent to those assessed in the study “are likely to be higher.”

And the overdiagnosis is particularly remarkable in the context of the true risk of thyroid cancer, senior author Salvatore Vaccarella, PhD, told this news organization.

“What is surprising is the magnitude of this. Without overdiagnosis, thyroid cancer would probably still be a relatively rare cancer,” he said.

“Currently, it is the fifth most commonly diagnosed cancer in women of all ages and is third in women under 50 years of age. And the rates are still rising fast.”

“Overdiagnosis of thyroid cancer is still rapidly expanding in many high-income countries, and for the first time, we document and quantify the phenomenon also for several middle-income socioeconomically transitioning countries,” he observed. “In short, it is a global public health problem.”

Guidelines, physicians: No symptoms should mean no screening

With the implications of overdiagnosis ranging from physical, psychological in terms of the patient, and significant personal as well as societal costs, most international guidelines explicitly recommend against screening asymptomatic individuals and call for active surveillance of microcarcinomas that are detected.

The messaging appears to be making a difference.

As reported in research by American authors discussing the thyroid cancer epidemic from a 2017 perspective, the overdiagnosis situation in South Korea prompted a group of physicians there to make a high-profile public appeal in print and on television recommending against thyroid screening with ultrasound.

The result was a 35% reduction in the number of thyroidectomies performed in the subsequent year.

“This seems to be a striking example that the issue of overdiagnosis and overtreatment resonates with patients, and that public awareness can lead to changes in behavior,” say the U.S. authors of that article.

Senior author Louise Davies, MD, of the VA Outcomes Group, in White River Junction, Vt., said in an interview that the new study sheds more light on this issue.

“Even though the data only go through 2012, I think they give a nice snapshot of what’s happening across the globe with thyroid cancer incidence in countries of different levels of development,” she said.

The findings underscore that “it’s important that people are educated about the limits of medical testing and that sometimes when we see abnormalities we are truly catching a cancer early, but sometimes we’re seeing things that have been there a long time and may not change or become a problem in the future,” Dr. Davies remarked.
 

Important to know what size of cancers are being detected

One particular concern about overdiagnosis in middle-income countries is that the common approach of active monitoring may be more difficult in these settings, Dr. Davies added.

“In order to manage overdiagnosis, the health care systems in those countries have to think about whether they have the infrastructure for active monitoring and whether the patients will show up for the monitoring – so that’s a challenge.”

Also, she noted that the new study does not detail the size of cancers detected.

“We don’t know much about the size of the cancers being detected and whether these are truly the small asymptomatic cancers that we are worried about being overdiagnosed.”

“Probably, at least some of what we’re seeing is appropriate detection of cancers that, before there was economic development, were in fact being missed and people were dying of,” she said.

“So while overdiagnosis can be occurring, some of this represents better detection of disease overall, and that’s a good thing actually.”

The authors and Dr. Davies have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The rapid increase in thyroid cancer incidence that has occurred since the 1990s – considered an “epidemic of overdiagnosis,” has extended beyond high-income countries to less affluent settings, where unnecessary – and sometimes opportunistic – screening could continue to thrive.

“The impact of overdiagnosis on the increasing incidence of thyroid cancer highlighted in our report is a warning sign for countries with growing economies, where diagnostic technologies are increasingly and routinely offered, usually in exchange for payment, despite evidence that the harms far outweigh benefits,” the authors say.

“Overdiagnosis could turn healthy people into patients, and expose them to unnecessary harms and lifelong treatments,” say Mengmeng Li, PhD, of the International Agency for Research on Cancer, Lyon, France, and colleagues in their article published in Lancet Diabetes & Endocrinology.

With their previous research showing high rates of overdiagnosis in high-income countries, for this new analysis, they sought to evaluate whether similar patterns were occurring in less affluent settings.

They examined data from population-based cancer registries in 26 countries on four continents, looking at all cases of thyroid cancer reported between 1998 and 2012 in men and women aged 15 to 84 years.
 

A global public health problem

The results showed that while the incidence of thyroid cancer steadily increased from 1998 to 2002 and from 2008 to 2012 in all high-income countries, similar trends were also seen in less affluent nations, particularly in Belarus, China, Colombia, and Lithuania.

The increases were consistently greater among middle-aged women aged 35-64 years in all countries.

To determine what proportion of the higher incidence was overdiagnosis, the authors turned to historic age-specific thyroid cancer incidence data prior to the introduction of ultrasound and then looked at the progressive departure from that pattern, likely the result of the increased detection by ultrasound of thyroid nodules in middle-aged adults.

The results showed the proportion of thyroid cancer cases in women estimated to be attributable to overdiagnosis between 2008 and 2012 was as much as 93% in South Korea, 91% in Belarus, 87% in China, 84% in Italy and Croatia, and 83% in Slovakia and France.

Proportions attributable to overdiagnosis were lower in Denmark (66%), Norway (65%), Ireland (63%), United Kingdom (58%), Japan (55%), and Thailand (44%).

Women were much more likely to be overdiagnosed than men, with an approximate ratio of 3:1 in all countries; however, mortality and prevalence of thyroid cancer in autopsies were similar between genders.

Although researchers only looked at data up until 2012, Dr. Li said that, even in that year, “the amplitude of the phenomenon” was “already large and is increasing rapidly over time.”

Figures for periods subsequent to those assessed in the study “are likely to be higher.”

And the overdiagnosis is particularly remarkable in the context of the true risk of thyroid cancer, senior author Salvatore Vaccarella, PhD, told this news organization.

“What is surprising is the magnitude of this. Without overdiagnosis, thyroid cancer would probably still be a relatively rare cancer,” he said.

“Currently, it is the fifth most commonly diagnosed cancer in women of all ages and is third in women under 50 years of age. And the rates are still rising fast.”

“Overdiagnosis of thyroid cancer is still rapidly expanding in many high-income countries, and for the first time, we document and quantify the phenomenon also for several middle-income socioeconomically transitioning countries,” he observed. “In short, it is a global public health problem.”

Guidelines, physicians: No symptoms should mean no screening

With the implications of overdiagnosis ranging from physical, psychological in terms of the patient, and significant personal as well as societal costs, most international guidelines explicitly recommend against screening asymptomatic individuals and call for active surveillance of microcarcinomas that are detected.

The messaging appears to be making a difference.

As reported in research by American authors discussing the thyroid cancer epidemic from a 2017 perspective, the overdiagnosis situation in South Korea prompted a group of physicians there to make a high-profile public appeal in print and on television recommending against thyroid screening with ultrasound.

The result was a 35% reduction in the number of thyroidectomies performed in the subsequent year.

“This seems to be a striking example that the issue of overdiagnosis and overtreatment resonates with patients, and that public awareness can lead to changes in behavior,” say the U.S. authors of that article.

Senior author Louise Davies, MD, of the VA Outcomes Group, in White River Junction, Vt., said in an interview that the new study sheds more light on this issue.

“Even though the data only go through 2012, I think they give a nice snapshot of what’s happening across the globe with thyroid cancer incidence in countries of different levels of development,” she said.

The findings underscore that “it’s important that people are educated about the limits of medical testing and that sometimes when we see abnormalities we are truly catching a cancer early, but sometimes we’re seeing things that have been there a long time and may not change or become a problem in the future,” Dr. Davies remarked.
 

Important to know what size of cancers are being detected

One particular concern about overdiagnosis in middle-income countries is that the common approach of active monitoring may be more difficult in these settings, Dr. Davies added.

“In order to manage overdiagnosis, the health care systems in those countries have to think about whether they have the infrastructure for active monitoring and whether the patients will show up for the monitoring – so that’s a challenge.”

Also, she noted that the new study does not detail the size of cancers detected.

“We don’t know much about the size of the cancers being detected and whether these are truly the small asymptomatic cancers that we are worried about being overdiagnosed.”

“Probably, at least some of what we’re seeing is appropriate detection of cancers that, before there was economic development, were in fact being missed and people were dying of,” she said.

“So while overdiagnosis can be occurring, some of this represents better detection of disease overall, and that’s a good thing actually.”

The authors and Dr. Davies have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The rapid increase in thyroid cancer incidence that has occurred since the 1990s – considered an “epidemic of overdiagnosis,” has extended beyond high-income countries to less affluent settings, where unnecessary – and sometimes opportunistic – screening could continue to thrive.

“The impact of overdiagnosis on the increasing incidence of thyroid cancer highlighted in our report is a warning sign for countries with growing economies, where diagnostic technologies are increasingly and routinely offered, usually in exchange for payment, despite evidence that the harms far outweigh benefits,” the authors say.

“Overdiagnosis could turn healthy people into patients, and expose them to unnecessary harms and lifelong treatments,” say Mengmeng Li, PhD, of the International Agency for Research on Cancer, Lyon, France, and colleagues in their article published in Lancet Diabetes & Endocrinology.

With their previous research showing high rates of overdiagnosis in high-income countries, for this new analysis, they sought to evaluate whether similar patterns were occurring in less affluent settings.

They examined data from population-based cancer registries in 26 countries on four continents, looking at all cases of thyroid cancer reported between 1998 and 2012 in men and women aged 15 to 84 years.
 

A global public health problem

The results showed that while the incidence of thyroid cancer steadily increased from 1998 to 2002 and from 2008 to 2012 in all high-income countries, similar trends were also seen in less affluent nations, particularly in Belarus, China, Colombia, and Lithuania.

The increases were consistently greater among middle-aged women aged 35-64 years in all countries.

To determine what proportion of the higher incidence was overdiagnosis, the authors turned to historic age-specific thyroid cancer incidence data prior to the introduction of ultrasound and then looked at the progressive departure from that pattern, likely the result of the increased detection by ultrasound of thyroid nodules in middle-aged adults.

The results showed the proportion of thyroid cancer cases in women estimated to be attributable to overdiagnosis between 2008 and 2012 was as much as 93% in South Korea, 91% in Belarus, 87% in China, 84% in Italy and Croatia, and 83% in Slovakia and France.

Proportions attributable to overdiagnosis were lower in Denmark (66%), Norway (65%), Ireland (63%), United Kingdom (58%), Japan (55%), and Thailand (44%).

Women were much more likely to be overdiagnosed than men, with an approximate ratio of 3:1 in all countries; however, mortality and prevalence of thyroid cancer in autopsies were similar between genders.

Although researchers only looked at data up until 2012, Dr. Li said that, even in that year, “the amplitude of the phenomenon” was “already large and is increasing rapidly over time.”

Figures for periods subsequent to those assessed in the study “are likely to be higher.”

And the overdiagnosis is particularly remarkable in the context of the true risk of thyroid cancer, senior author Salvatore Vaccarella, PhD, told this news organization.

“What is surprising is the magnitude of this. Without overdiagnosis, thyroid cancer would probably still be a relatively rare cancer,” he said.

“Currently, it is the fifth most commonly diagnosed cancer in women of all ages and is third in women under 50 years of age. And the rates are still rising fast.”

“Overdiagnosis of thyroid cancer is still rapidly expanding in many high-income countries, and for the first time, we document and quantify the phenomenon also for several middle-income socioeconomically transitioning countries,” he observed. “In short, it is a global public health problem.”

Guidelines, physicians: No symptoms should mean no screening

With the implications of overdiagnosis ranging from physical, psychological in terms of the patient, and significant personal as well as societal costs, most international guidelines explicitly recommend against screening asymptomatic individuals and call for active surveillance of microcarcinomas that are detected.

The messaging appears to be making a difference.

As reported in research by American authors discussing the thyroid cancer epidemic from a 2017 perspective, the overdiagnosis situation in South Korea prompted a group of physicians there to make a high-profile public appeal in print and on television recommending against thyroid screening with ultrasound.

The result was a 35% reduction in the number of thyroidectomies performed in the subsequent year.

“This seems to be a striking example that the issue of overdiagnosis and overtreatment resonates with patients, and that public awareness can lead to changes in behavior,” say the U.S. authors of that article.

Senior author Louise Davies, MD, of the VA Outcomes Group, in White River Junction, Vt., said in an interview that the new study sheds more light on this issue.

“Even though the data only go through 2012, I think they give a nice snapshot of what’s happening across the globe with thyroid cancer incidence in countries of different levels of development,” she said.

The findings underscore that “it’s important that people are educated about the limits of medical testing and that sometimes when we see abnormalities we are truly catching a cancer early, but sometimes we’re seeing things that have been there a long time and may not change or become a problem in the future,” Dr. Davies remarked.
 

Important to know what size of cancers are being detected

One particular concern about overdiagnosis in middle-income countries is that the common approach of active monitoring may be more difficult in these settings, Dr. Davies added.

“In order to manage overdiagnosis, the health care systems in those countries have to think about whether they have the infrastructure for active monitoring and whether the patients will show up for the monitoring – so that’s a challenge.”

Also, she noted that the new study does not detail the size of cancers detected.

“We don’t know much about the size of the cancers being detected and whether these are truly the small asymptomatic cancers that we are worried about being overdiagnosed.”

“Probably, at least some of what we’re seeing is appropriate detection of cancers that, before there was economic development, were in fact being missed and people were dying of,” she said.

“So while overdiagnosis can be occurring, some of this represents better detection of disease overall, and that’s a good thing actually.”

The authors and Dr. Davies have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A treat-to-target strategy for managing patients with axial spondyloarthritis failed to meet its primary efficacy endpoint but still showed several suggestive indications of benefit compared with usual care in a multicenter, randomized study with 160 patients.

The treat-to-target management strategy tested aimed to get patients to an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1, as recommended for patients with axial spondyloarthritis (axSpA) by an international task force. Also notable about the study was its primary endpoint, at least a 30% improvement in the Assessment of Spondyloarthritis International Society Health Index (ASAS HI), a measure of health-related quality-of-life that the study organizers selected in part because of its distinction from the treatment target.

“For the first time in rheumatology, we targeted inflammation to have an impact on another domain of the disease. Despite not reaching statistical significance, we see a difference between the groups,” Anna Moltó, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

After 12 months in the study, the 80 axSpA patients assigned to the treat-to-target regimen had a 47% rate of attainment of the primary endpoint, compared with 36% of the 80 patients assigned to usual care, an 11% absolute between-group difference with a P value that came close to but failed to achieve the conventional standard of statistical significance after adjustment for potential confounders (P = .09). Six secondary outcomes showed statistically significant improvements compared with the control patients, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the ASAS 20, and ASAS 40. Five additional metrics showed nominal between-group improvements with the treat-to-target strategy that were not statistically significant, including various forms of the ASDAS.

One additional notable finding came from a cost-efficacy analysis run by Dr. Moltó and associates, which showed that the treat-to-target strategy was “dominant” over usual care by producing both better outcomes as well as a lower total cost, compared with control patients, even though twice as many patients on the treat-to-target strategy received a biologic disease-modifying antirheumatic drug (bDMARD) compared with patients in the usual care group. The incremental cost utility ratio for treat-to-target was 19,430 euros (about $22,000) per quality-adjusted life-year gained, putting the strategy into the range of a “cost effective” approach, and the two treatment arms also had comparable safety, said Dr. Moltó, a rheumatologist at Cochin Hospital in Paris.

The 11% increase in treat-to-target patients achieving at least a 30% improvement in their ASAS HI score “is potentially clinically relevant” because the comparator arm in the study received “very active” usual care and was not by any measure a true placebo control group, noted Maxime Dougados, MD, a rheumatologist and professor or medicine at Cochin Hospital and senior investigator for the study. In general, in treatment studies of rheumatologic diseases a 10% or greater absolute increase in the incidence of a beneficial outcome is considered clinically meaningful when compared with an actively-treated control arm, he noted.

“Using the ASAS HI score was very ambitious for the study, and it’s a very relevant outcome,” said Sofia Ramiro, MD, a rheumatologist at Leiden (the Netherlands) University Medical Center who was not associated with the study and chaired the session where Dr. Moltó gave her report. “We have had treat-to-target trials that showed benefit when disease activity was the endpoint.” But when a study “targets treatment to [reducing] disease activity and then uses disease activity as the outcome measure you expect to see an effect, but it is circular reasoning and we are left with challenges in interpreting the results. Now we have a trial that is formally [neutral] but with a different, more ambitious endpoint. All the indications are for benefit from treat-to-target for both the primary endpoint and for all the other endpoints.”

“We were in a difficult situation when choosing the outcome. We didn’t know whether a 30% improvement in the ASAS HI was really relevant, but it seems to be,” said Désirée van der Heijde, MD, a rheumatologist and professor of medicine at Leiden University Medical Center and a collaborator on Dr. Moltó’s study. “I’d choose ASAS HI again as a primary endpoint” for a treat-to-target study in patients with axSpA, she said, but added that a 30% improvement in this score as the response threshold may warrant reconsideration. Both Dr. van der Heijde and Dr. Dougados agreed that at least one additional study with a somewhat similar design is needed to better document and confirm a role for a treat-to-target strategy in axSpA patients.

The Tight Control in Spondyloarthritis (TICOSPA) study ran at 10 French centers and 4 centers each in Belgium and the Netherlands. The study enrolled adults with rheumatologist-diagnosed axSpA with an ASDAS score greater than 2.1 who had not yet received a bDMARD, had not yet maxed out on their dosage of NSAIDs, and had certain baseline immunologic and imaging findings available. The researchers randomized 160 patients to either treat-to-target or usual care management by the center they attended to prevent cross contamination of management strategies. The treat-to-target regimen involved office examinations and consultations every 4 weeks rather than every 3 months with usual care, and also required a predefined management strategy with treatment prompts based on the strategy sent to the treating clinicians via the EMR. The average age of the patients was 38 years, they had been diagnosed with axSpA for an average of just under 4 years, and their mean ASDAS score at entry was 3. During the 12 months of management, 56% of the patients in the treat-to-target arm initiated treatment with a bDMARD, compared with 28% among the controls. Use of NSAIDs was similar between the two study subgroups.

TICOSPA was sponsored by UCB. Dr. Moltó has been a consultant to and received research funding from AbbVie, Bristol-Myers Squibb, Merck, Pfizer, and UCB. Dr. Dougados has had financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Merck, Pfizer, and UCB. Dr. van der Heijde has had financial relationships with more than 20 companies including UCB. Dr. Ramiro had been a consultant to or received research funding from AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, and Sanofi.

mzoler@mdedge.com

SOURCE: Moltó A et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:413.

A treat-to-target strategy for managing patients with axial spondyloarthritis failed to meet its primary efficacy endpoint but still showed several suggestive indications of benefit compared with usual care in a multicenter, randomized study with 160 patients.

The treat-to-target management strategy tested aimed to get patients to an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1, as recommended for patients with axial spondyloarthritis (axSpA) by an international task force. Also notable about the study was its primary endpoint, at least a 30% improvement in the Assessment of Spondyloarthritis International Society Health Index (ASAS HI), a measure of health-related quality-of-life that the study organizers selected in part because of its distinction from the treatment target.

“For the first time in rheumatology, we targeted inflammation to have an impact on another domain of the disease. Despite not reaching statistical significance, we see a difference between the groups,” Anna Moltó, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

After 12 months in the study, the 80 axSpA patients assigned to the treat-to-target regimen had a 47% rate of attainment of the primary endpoint, compared with 36% of the 80 patients assigned to usual care, an 11% absolute between-group difference with a P value that came close to but failed to achieve the conventional standard of statistical significance after adjustment for potential confounders (P = .09). Six secondary outcomes showed statistically significant improvements compared with the control patients, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the ASAS 20, and ASAS 40. Five additional metrics showed nominal between-group improvements with the treat-to-target strategy that were not statistically significant, including various forms of the ASDAS.

One additional notable finding came from a cost-efficacy analysis run by Dr. Moltó and associates, which showed that the treat-to-target strategy was “dominant” over usual care by producing both better outcomes as well as a lower total cost, compared with control patients, even though twice as many patients on the treat-to-target strategy received a biologic disease-modifying antirheumatic drug (bDMARD) compared with patients in the usual care group. The incremental cost utility ratio for treat-to-target was 19,430 euros (about $22,000) per quality-adjusted life-year gained, putting the strategy into the range of a “cost effective” approach, and the two treatment arms also had comparable safety, said Dr. Moltó, a rheumatologist at Cochin Hospital in Paris.

The 11% increase in treat-to-target patients achieving at least a 30% improvement in their ASAS HI score “is potentially clinically relevant” because the comparator arm in the study received “very active” usual care and was not by any measure a true placebo control group, noted Maxime Dougados, MD, a rheumatologist and professor or medicine at Cochin Hospital and senior investigator for the study. In general, in treatment studies of rheumatologic diseases a 10% or greater absolute increase in the incidence of a beneficial outcome is considered clinically meaningful when compared with an actively-treated control arm, he noted.

“Using the ASAS HI score was very ambitious for the study, and it’s a very relevant outcome,” said Sofia Ramiro, MD, a rheumatologist at Leiden (the Netherlands) University Medical Center who was not associated with the study and chaired the session where Dr. Moltó gave her report. “We have had treat-to-target trials that showed benefit when disease activity was the endpoint.” But when a study “targets treatment to [reducing] disease activity and then uses disease activity as the outcome measure you expect to see an effect, but it is circular reasoning and we are left with challenges in interpreting the results. Now we have a trial that is formally [neutral] but with a different, more ambitious endpoint. All the indications are for benefit from treat-to-target for both the primary endpoint and for all the other endpoints.”

“We were in a difficult situation when choosing the outcome. We didn’t know whether a 30% improvement in the ASAS HI was really relevant, but it seems to be,” said Désirée van der Heijde, MD, a rheumatologist and professor of medicine at Leiden University Medical Center and a collaborator on Dr. Moltó’s study. “I’d choose ASAS HI again as a primary endpoint” for a treat-to-target study in patients with axSpA, she said, but added that a 30% improvement in this score as the response threshold may warrant reconsideration. Both Dr. van der Heijde and Dr. Dougados agreed that at least one additional study with a somewhat similar design is needed to better document and confirm a role for a treat-to-target strategy in axSpA patients.

The Tight Control in Spondyloarthritis (TICOSPA) study ran at 10 French centers and 4 centers each in Belgium and the Netherlands. The study enrolled adults with rheumatologist-diagnosed axSpA with an ASDAS score greater than 2.1 who had not yet received a bDMARD, had not yet maxed out on their dosage of NSAIDs, and had certain baseline immunologic and imaging findings available. The researchers randomized 160 patients to either treat-to-target or usual care management by the center they attended to prevent cross contamination of management strategies. The treat-to-target regimen involved office examinations and consultations every 4 weeks rather than every 3 months with usual care, and also required a predefined management strategy with treatment prompts based on the strategy sent to the treating clinicians via the EMR. The average age of the patients was 38 years, they had been diagnosed with axSpA for an average of just under 4 years, and their mean ASDAS score at entry was 3. During the 12 months of management, 56% of the patients in the treat-to-target arm initiated treatment with a bDMARD, compared with 28% among the controls. Use of NSAIDs was similar between the two study subgroups.

TICOSPA was sponsored by UCB. Dr. Moltó has been a consultant to and received research funding from AbbVie, Bristol-Myers Squibb, Merck, Pfizer, and UCB. Dr. Dougados has had financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Merck, Pfizer, and UCB. Dr. van der Heijde has had financial relationships with more than 20 companies including UCB. Dr. Ramiro had been a consultant to or received research funding from AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, and Sanofi.

mzoler@mdedge.com

SOURCE: Moltó A et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:413.

A treat-to-target strategy for managing patients with axial spondyloarthritis failed to meet its primary efficacy endpoint but still showed several suggestive indications of benefit compared with usual care in a multicenter, randomized study with 160 patients.

The treat-to-target management strategy tested aimed to get patients to an Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 2.1, as recommended for patients with axial spondyloarthritis (axSpA) by an international task force. Also notable about the study was its primary endpoint, at least a 30% improvement in the Assessment of Spondyloarthritis International Society Health Index (ASAS HI), a measure of health-related quality-of-life that the study organizers selected in part because of its distinction from the treatment target.

“For the first time in rheumatology, we targeted inflammation to have an impact on another domain of the disease. Despite not reaching statistical significance, we see a difference between the groups,” Anna Moltó, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

After 12 months in the study, the 80 axSpA patients assigned to the treat-to-target regimen had a 47% rate of attainment of the primary endpoint, compared with 36% of the 80 patients assigned to usual care, an 11% absolute between-group difference with a P value that came close to but failed to achieve the conventional standard of statistical significance after adjustment for potential confounders (P = .09). Six secondary outcomes showed statistically significant improvements compared with the control patients, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the ASAS 20, and ASAS 40. Five additional metrics showed nominal between-group improvements with the treat-to-target strategy that were not statistically significant, including various forms of the ASDAS.

One additional notable finding came from a cost-efficacy analysis run by Dr. Moltó and associates, which showed that the treat-to-target strategy was “dominant” over usual care by producing both better outcomes as well as a lower total cost, compared with control patients, even though twice as many patients on the treat-to-target strategy received a biologic disease-modifying antirheumatic drug (bDMARD) compared with patients in the usual care group. The incremental cost utility ratio for treat-to-target was 19,430 euros (about $22,000) per quality-adjusted life-year gained, putting the strategy into the range of a “cost effective” approach, and the two treatment arms also had comparable safety, said Dr. Moltó, a rheumatologist at Cochin Hospital in Paris.

The 11% increase in treat-to-target patients achieving at least a 30% improvement in their ASAS HI score “is potentially clinically relevant” because the comparator arm in the study received “very active” usual care and was not by any measure a true placebo control group, noted Maxime Dougados, MD, a rheumatologist and professor or medicine at Cochin Hospital and senior investigator for the study. In general, in treatment studies of rheumatologic diseases a 10% or greater absolute increase in the incidence of a beneficial outcome is considered clinically meaningful when compared with an actively-treated control arm, he noted.

“Using the ASAS HI score was very ambitious for the study, and it’s a very relevant outcome,” said Sofia Ramiro, MD, a rheumatologist at Leiden (the Netherlands) University Medical Center who was not associated with the study and chaired the session where Dr. Moltó gave her report. “We have had treat-to-target trials that showed benefit when disease activity was the endpoint.” But when a study “targets treatment to [reducing] disease activity and then uses disease activity as the outcome measure you expect to see an effect, but it is circular reasoning and we are left with challenges in interpreting the results. Now we have a trial that is formally [neutral] but with a different, more ambitious endpoint. All the indications are for benefit from treat-to-target for both the primary endpoint and for all the other endpoints.”

“We were in a difficult situation when choosing the outcome. We didn’t know whether a 30% improvement in the ASAS HI was really relevant, but it seems to be,” said Désirée van der Heijde, MD, a rheumatologist and professor of medicine at Leiden University Medical Center and a collaborator on Dr. Moltó’s study. “I’d choose ASAS HI again as a primary endpoint” for a treat-to-target study in patients with axSpA, she said, but added that a 30% improvement in this score as the response threshold may warrant reconsideration. Both Dr. van der Heijde and Dr. Dougados agreed that at least one additional study with a somewhat similar design is needed to better document and confirm a role for a treat-to-target strategy in axSpA patients.

The Tight Control in Spondyloarthritis (TICOSPA) study ran at 10 French centers and 4 centers each in Belgium and the Netherlands. The study enrolled adults with rheumatologist-diagnosed axSpA with an ASDAS score greater than 2.1 who had not yet received a bDMARD, had not yet maxed out on their dosage of NSAIDs, and had certain baseline immunologic and imaging findings available. The researchers randomized 160 patients to either treat-to-target or usual care management by the center they attended to prevent cross contamination of management strategies. The treat-to-target regimen involved office examinations and consultations every 4 weeks rather than every 3 months with usual care, and also required a predefined management strategy with treatment prompts based on the strategy sent to the treating clinicians via the EMR. The average age of the patients was 38 years, they had been diagnosed with axSpA for an average of just under 4 years, and their mean ASDAS score at entry was 3. During the 12 months of management, 56% of the patients in the treat-to-target arm initiated treatment with a bDMARD, compared with 28% among the controls. Use of NSAIDs was similar between the two study subgroups.

TICOSPA was sponsored by UCB. Dr. Moltó has been a consultant to and received research funding from AbbVie, Bristol-Myers Squibb, Merck, Pfizer, and UCB. Dr. Dougados has had financial relationships with AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Merck, Pfizer, and UCB. Dr. van der Heijde has had financial relationships with more than 20 companies including UCB. Dr. Ramiro had been a consultant to or received research funding from AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, and Sanofi.

mzoler@mdedge.com

SOURCE: Moltó A et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:413.

For patients with immune checkpoint inhibitor–induced colitis, Epstein-Barr virus (EBV) infection may increase risks of steroid-refractory disease and ulcers that contribute to colonic perforation, according to investigators.

Pending further research, routine monitoring of EBV status may be needed for patients undergoing checkpoint inhibitor therapy, reported lead author Matthew R. Pugh, FRCPath, of University Hospital of Wales, Cardiff, and colleagues.

“Few studies have investigated the role of viruses in the pathogenesis of immune-related colitis,” the investigators wrote. Their report is in Clinical Gastroenterology and Hepatology. While cytomegalovirus has been linked with worse disease, no studies to date have evaluated the role of EBV, they noted, despite theoretical concerns.

“A spectrum of EBV-positive lymphoproliferations shows a predilection for the GI tract, ranging from indolent lesions to aggressive lymphomas,” the investigators wrote. “One such proliferation, EBV-positive mucocutaneous ulcer (EBVMCU), is an indolent, ulcerating process associated with immunosuppression,” they added, referring to studies involving patients with inflammatory bowel disease.

To determine if EBV could be playing a similar role in cancer immunotherapy, the investigators retrospectively analyzed colon tissue samples from 16 patients who developed colitis after undergoing immune checkpoint inhibitor therapy between 2010 and 2018. Thirteen patients received an anti-CTLA-4 agent, three were treated with a PD-1 inhibitor, and four received both types of therapy. Most patients had advanced-stage melanoma (n = 14), while the remaining two patients had prostate and renal carcinoma, respectively. Ten samples were biopsies, whereas four specimens were collected from surgical repair of colon perforation.

EBV status was determined by chromogenic in situ hybridization for EBV-encoded small RNA, with positive samples further characterized by immunohistochemistry for CD3, CD15, CD20, CD30, CD138, MUM1, and PAX5. In addition, all samples were immunostained for cytomegalovirus, and PCR was used to assess B cell and T cell clonality.

The median time from induction of therapy to colitis onset was approximately 1 month (32.5 days), with symptoms typically lasting 3 weeks (22.5 days). Macroscopically, 10 patients had ulceration, and 6 displayed signs of hemorrhage.

EBVMCUs were found in four patients, of whom three had received anti-CTLA-4 therapy, one had received both anti-CTLA-4 and anti-PD-1 therapy, and all had undergone colonic resection. One case also tested positive for cytomegalovirus.

Immunostaining showed that EBVMCUs had underlying B cell and linear plasma cell infiltrates, with “a rim of small T lymphocytes at the base.” EBV-encoded small RNA expression was found in both plasma cells and small B cells.

The presence of EBVMCUs was significantly associated with more severe colitis.

All four EBV-positive patients had steroid-refractory colitis, compared with only two (12.5%) of the EBV-negative patients (P = .008), a difference that was echoed by the rate of colonic resection (100% vs. 12.5%; P .008). Furthermore, colon perforation occurred in all EBV-positive patients, versus none of the EBV-negative patients (P = .001).

For three EBV-positive patients, preresection biopsy samples were available, allowing for temporal analysis of EBV-encoded small RNA. Earlier samples had reduced or absent EBV-positive lymphoid cells, which offered some etiologic insight.

“The apparent absence or paucity of EBV-positive lymphoid cells in biopsies taken before resection suggests that EBVMCU is arising within preexisting immune-mediated inflammation rather than EBV driving the initial inflammatory insult,” the investigators wrote.

They suggested that EBVMCUs “likely contribute directly to colonic perforation,” since lesions are characterized by a form of localized tissue destruction that has been previously associated with colonic perforation in Crohn’s disease and intestinal perforation in rheumatoid arthritis.

Still, mechanisms of action remain unknown. “It is unclear why EBVMCUs should arise in the context of immune checkpoint regulator therapy, which, in contrast to conventional immunosuppressants, results in immune activation,” the investigators wrote. “It is possible that these patients may harbor residual immunosuppression resulting from their disease burden, advanced age, and prior immunosuppression.”

While more work is needed, Dr. Pugh and colleagues suggested that EBV testing may be valuable for some patients.

“The findings support the need for further studies investigating the role of EBV monitoring in immune checkpoint regulator therapy, which is not currently part of routine protocols.”

The study was funded by All Wales Lymphoma Panel. The investigators disclosed no conflicts of interest.

SOURCE: Pugh et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.09.031.

For patients with immune checkpoint inhibitor–induced colitis, Epstein-Barr virus (EBV) infection may increase risks of steroid-refractory disease and ulcers that contribute to colonic perforation, according to investigators.

Pending further research, routine monitoring of EBV status may be needed for patients undergoing checkpoint inhibitor therapy, reported lead author Matthew R. Pugh, FRCPath, of University Hospital of Wales, Cardiff, and colleagues.

“Few studies have investigated the role of viruses in the pathogenesis of immune-related colitis,” the investigators wrote. Their report is in Clinical Gastroenterology and Hepatology. While cytomegalovirus has been linked with worse disease, no studies to date have evaluated the role of EBV, they noted, despite theoretical concerns.

“A spectrum of EBV-positive lymphoproliferations shows a predilection for the GI tract, ranging from indolent lesions to aggressive lymphomas,” the investigators wrote. “One such proliferation, EBV-positive mucocutaneous ulcer (EBVMCU), is an indolent, ulcerating process associated with immunosuppression,” they added, referring to studies involving patients with inflammatory bowel disease.

To determine if EBV could be playing a similar role in cancer immunotherapy, the investigators retrospectively analyzed colon tissue samples from 16 patients who developed colitis after undergoing immune checkpoint inhibitor therapy between 2010 and 2018. Thirteen patients received an anti-CTLA-4 agent, three were treated with a PD-1 inhibitor, and four received both types of therapy. Most patients had advanced-stage melanoma (n = 14), while the remaining two patients had prostate and renal carcinoma, respectively. Ten samples were biopsies, whereas four specimens were collected from surgical repair of colon perforation.

EBV status was determined by chromogenic in situ hybridization for EBV-encoded small RNA, with positive samples further characterized by immunohistochemistry for CD3, CD15, CD20, CD30, CD138, MUM1, and PAX5. In addition, all samples were immunostained for cytomegalovirus, and PCR was used to assess B cell and T cell clonality.

The median time from induction of therapy to colitis onset was approximately 1 month (32.5 days), with symptoms typically lasting 3 weeks (22.5 days). Macroscopically, 10 patients had ulceration, and 6 displayed signs of hemorrhage.

EBVMCUs were found in four patients, of whom three had received anti-CTLA-4 therapy, one had received both anti-CTLA-4 and anti-PD-1 therapy, and all had undergone colonic resection. One case also tested positive for cytomegalovirus.

Immunostaining showed that EBVMCUs had underlying B cell and linear plasma cell infiltrates, with “a rim of small T lymphocytes at the base.” EBV-encoded small RNA expression was found in both plasma cells and small B cells.

The presence of EBVMCUs was significantly associated with more severe colitis.

All four EBV-positive patients had steroid-refractory colitis, compared with only two (12.5%) of the EBV-negative patients (P = .008), a difference that was echoed by the rate of colonic resection (100% vs. 12.5%; P .008). Furthermore, colon perforation occurred in all EBV-positive patients, versus none of the EBV-negative patients (P = .001).

For three EBV-positive patients, preresection biopsy samples were available, allowing for temporal analysis of EBV-encoded small RNA. Earlier samples had reduced or absent EBV-positive lymphoid cells, which offered some etiologic insight.

“The apparent absence or paucity of EBV-positive lymphoid cells in biopsies taken before resection suggests that EBVMCU is arising within preexisting immune-mediated inflammation rather than EBV driving the initial inflammatory insult,” the investigators wrote.

They suggested that EBVMCUs “likely contribute directly to colonic perforation,” since lesions are characterized by a form of localized tissue destruction that has been previously associated with colonic perforation in Crohn’s disease and intestinal perforation in rheumatoid arthritis.

Still, mechanisms of action remain unknown. “It is unclear why EBVMCUs should arise in the context of immune checkpoint regulator therapy, which, in contrast to conventional immunosuppressants, results in immune activation,” the investigators wrote. “It is possible that these patients may harbor residual immunosuppression resulting from their disease burden, advanced age, and prior immunosuppression.”

While more work is needed, Dr. Pugh and colleagues suggested that EBV testing may be valuable for some patients.

“The findings support the need for further studies investigating the role of EBV monitoring in immune checkpoint regulator therapy, which is not currently part of routine protocols.”

The study was funded by All Wales Lymphoma Panel. The investigators disclosed no conflicts of interest.

SOURCE: Pugh et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.09.031.

For patients with immune checkpoint inhibitor–induced colitis, Epstein-Barr virus (EBV) infection may increase risks of steroid-refractory disease and ulcers that contribute to colonic perforation, according to investigators.

Pending further research, routine monitoring of EBV status may be needed for patients undergoing checkpoint inhibitor therapy, reported lead author Matthew R. Pugh, FRCPath, of University Hospital of Wales, Cardiff, and colleagues.

“Few studies have investigated the role of viruses in the pathogenesis of immune-related colitis,” the investigators wrote. Their report is in Clinical Gastroenterology and Hepatology. While cytomegalovirus has been linked with worse disease, no studies to date have evaluated the role of EBV, they noted, despite theoretical concerns.

“A spectrum of EBV-positive lymphoproliferations shows a predilection for the GI tract, ranging from indolent lesions to aggressive lymphomas,” the investigators wrote. “One such proliferation, EBV-positive mucocutaneous ulcer (EBVMCU), is an indolent, ulcerating process associated with immunosuppression,” they added, referring to studies involving patients with inflammatory bowel disease.

To determine if EBV could be playing a similar role in cancer immunotherapy, the investigators retrospectively analyzed colon tissue samples from 16 patients who developed colitis after undergoing immune checkpoint inhibitor therapy between 2010 and 2018. Thirteen patients received an anti-CTLA-4 agent, three were treated with a PD-1 inhibitor, and four received both types of therapy. Most patients had advanced-stage melanoma (n = 14), while the remaining two patients had prostate and renal carcinoma, respectively. Ten samples were biopsies, whereas four specimens were collected from surgical repair of colon perforation.

EBV status was determined by chromogenic in situ hybridization for EBV-encoded small RNA, with positive samples further characterized by immunohistochemistry for CD3, CD15, CD20, CD30, CD138, MUM1, and PAX5. In addition, all samples were immunostained for cytomegalovirus, and PCR was used to assess B cell and T cell clonality.

The median time from induction of therapy to colitis onset was approximately 1 month (32.5 days), with symptoms typically lasting 3 weeks (22.5 days). Macroscopically, 10 patients had ulceration, and 6 displayed signs of hemorrhage.

EBVMCUs were found in four patients, of whom three had received anti-CTLA-4 therapy, one had received both anti-CTLA-4 and anti-PD-1 therapy, and all had undergone colonic resection. One case also tested positive for cytomegalovirus.

Immunostaining showed that EBVMCUs had underlying B cell and linear plasma cell infiltrates, with “a rim of small T lymphocytes at the base.” EBV-encoded small RNA expression was found in both plasma cells and small B cells.

The presence of EBVMCUs was significantly associated with more severe colitis.

All four EBV-positive patients had steroid-refractory colitis, compared with only two (12.5%) of the EBV-negative patients (P = .008), a difference that was echoed by the rate of colonic resection (100% vs. 12.5%; P .008). Furthermore, colon perforation occurred in all EBV-positive patients, versus none of the EBV-negative patients (P = .001).

For three EBV-positive patients, preresection biopsy samples were available, allowing for temporal analysis of EBV-encoded small RNA. Earlier samples had reduced or absent EBV-positive lymphoid cells, which offered some etiologic insight.

“The apparent absence or paucity of EBV-positive lymphoid cells in biopsies taken before resection suggests that EBVMCU is arising within preexisting immune-mediated inflammation rather than EBV driving the initial inflammatory insult,” the investigators wrote.

They suggested that EBVMCUs “likely contribute directly to colonic perforation,” since lesions are characterized by a form of localized tissue destruction that has been previously associated with colonic perforation in Crohn’s disease and intestinal perforation in rheumatoid arthritis.

Still, mechanisms of action remain unknown. “It is unclear why EBVMCUs should arise in the context of immune checkpoint regulator therapy, which, in contrast to conventional immunosuppressants, results in immune activation,” the investigators wrote. “It is possible that these patients may harbor residual immunosuppression resulting from their disease burden, advanced age, and prior immunosuppression.”

While more work is needed, Dr. Pugh and colleagues suggested that EBV testing may be valuable for some patients.

“The findings support the need for further studies investigating the role of EBV monitoring in immune checkpoint regulator therapy, which is not currently part of routine protocols.”

The study was funded by All Wales Lymphoma Panel. The investigators disclosed no conflicts of interest.

SOURCE: Pugh et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.09.031.

Click here to read. 

Supplement Faculty

Perry Shieh, MD, PhD
Professor
Department of Neurology
David Geffen School
of Medicine at UCLA
Ronald Reagan UCLA
Medical Center
Los Angeles, CA

Sally Dunaway Young, PT, DPT
Physical Therapist
and Clinical Research
Evaluator/Manager
Stanford University School
of Medicine
Stanford, CA

Click here to read. 

Supplement Faculty

Perry Shieh, MD, PhD
Professor
Department of Neurology
David Geffen School
of Medicine at UCLA
Ronald Reagan UCLA
Medical Center
Los Angeles, CA

Sally Dunaway Young, PT, DPT
Physical Therapist
and Clinical Research
Evaluator/Manager
Stanford University School
of Medicine
Stanford, CA

Click here to read. 

Supplement Faculty

Perry Shieh, MD, PhD
Professor
Department of Neurology
David Geffen School
of Medicine at UCLA
Ronald Reagan UCLA
Medical Center
Los Angeles, CA

Sally Dunaway Young, PT, DPT
Physical Therapist
and Clinical Research
Evaluator/Manager
Stanford University School
of Medicine
Stanford, CA

It is clear that the coronavirus 2019 disease (COVID-19) pandemic is one of the most extraordinary epochs of our professional and personal lives. Besides the challenges to the techniques and technologies of care for this illness, we are seeing challenges to the fundamentals of health care, both to the systems whereby it is delivered, and to the ethical principles that guide that delivery. There is unprecedented relevance of certain ethical issues in the practice of medicine, many of which have previously been discussed in classrooms and textbooks, but now are at play in daily practice, particularly at the frontlines of the war against COVID-19.¹ In this article, I highlight several ethical dilemmas that are salient to these unique times. Some of the most compelling issues can be sorted into 2 clearly overlapping domains: triage ethics and equity ethics.

Triage ethics

In the areas most greatly affected by the COVID-19 pandemic, scarcity of treatment resources, such as ventilators, is a legitimate concern. French surgeon Dominique Jean Larry was the first to establish medical sorting protocols in the context of the battles of the Napoleonic wars, for which he used the French word triage, meaning “sorting.”² He articulated 3 prognostic categories: 1) those who would die even with treatment, 2) those who would live without treatment, and 3) those who would die unless treated. Triage decisions arise in the context of insufficient resources, particularly space, staff, and supplies. Although usually identified with disasters, these decisions can arise in other contexts where personnel or technological resources are inadequate. Indeed, one of the first modern incarnations of triage ethics in American civilian life was in the early days of hemodialysis, when so-called “God committees” made complex decisions about which patients would be able to use this new, rare technology.³

Two fundamental moral constructs undergird medical ethics: deontological and utilitarian. The former, in which most clinicians traffic in ordinary practice, is driven by principles or moral rules such as the sanctity of life, the rule of fairness, and the principle of autonomy.⁴ They apply primarily in the context of treating an individual patient. The utilitarian way of reasoning is not as familiar to clinicians. It is focused on the broader context, the common good, the health of the group. It asks to calculate “the greatest good for the greatest number” as a means of navigating ethical dilemmas.⁵ The utilitarian perspective is far more familiar to policymakers, health care administrators, and public health professionals. It tends to be anathema to clinicians. However, disasters such as the COVID-19 pandemic ask some clinicians, particularly inpatient physicians, to shift from their usual deontological perspective to a utilitarian one, because triage ethics fundamentally draw on utilitarian reasoning. This can be quite anguishing to clinicians who typically work with individual patients in settings of more adequate, if not abundant, resources. What may feel wrong in a deontological mode can be seen as ethically right in a utilitarian framework.

The Table compares and contrasts these 2 paradigms and how they manifest in the clinical trenches, in a protracted health care crisis with limited resources.

The COVID-19 crisis has produced an unprecedented and extended exposure of clinicians to triage situations in the face of limited resources such as ventilators, personnel, personal protective equipment, etc.⁶ Numerous possible approaches to deploying limited supplies are being considered. On what basis should such decisions be made? How can fairness be optimally manifest? Some possibilities include:

• first come, first served
• youngest first
• lottery
• short-term survivability
• long-term prognosis for quality of life
• value of a patient to the lives of others (eg, parents, health care workers, vaccine researchers).

One particularly interesting exploration of these questions was done in Maryland and reported in the “Maryland Framework for the Allocation of Scarce Life-sustaining Medical Resources in a Catastrophic Public Health Emergency.”⁷ This was the product of a multi-year consultation, ending in 2017, with several constituencies, including clinicians, politicians, hospital administrators, and members of the public brainstorming about approaches to allocating a hypothetical scarcity of ventilators. Interestingly, there was one broad consensus among these groups: a ventilator should not be withdrawn from a patient already using it to give to a “better” candidate who comes along later.

Some institutions have developed a method of making triage decisions that takes such decisions out of the hands of individual clinicians and instead assigns them to specialized “triage teams” made up of ethicists and clinicians experienced in critical care, to develop more distance from the emotions at the bedside. To minimize bias, such teams are often insulated from getting personal information about the patient, and receive only acute clinical information.⁸

Continue to: The pros and cons of these approaches...

The pros and cons of these approaches and the underlying ethical reasoning is beyond the scope of this overview. Policy documents from different states, regions, nations, and institutions have various approaches to making these choices. Presently, there is no coherent national or international agreement on triage ethics.⁹ It is important, however, that there be transparency in whatever approach an institution adopts for triage decisions.

Equity ethics

Though the equitable distribution of health care delivery has long been a concern, this problem has become magnified by the COVID-19 crisis. Race, sex, age, socioeconomic class, and type of illness have all been perennial sources of division between those who have better or worse access to health care and its outcomes. All of these distinctions have created differentials in rates of cases, hospitalizations, and deaths in the COVID-19 pandemic.¹⁰

The shifting of acute health care facilities to mostly COVID-19–related treatment, and postponing less critical and more “elective” care, creates a divide based on illness type. Many facilities have stopped taking admissions for other kinds of cases. This is particularly relevant to psychiatric units, many of which have had to decrease their bed capacities to make all rooms private, and limit their usual treatments offered to inpatients.¹¹ Many long-term units, such as at state hospitals, are closing to new admissions. Many day hospitals and intensive outpatient programs remain closed, not even shifting to telehealth. In areas most affected by COVID-19, some institutions have closed psychiatric wards and reallocated psychiatrists to cover some of the medical units. So the availability of the more intensive, institutionally-based levels of care is significantly reduced, particularly for psychiatric patients.¹² These patients already are a disadvantaged population in the distribution of health care resources, and the care of individuals with serious mental illness is more likely to be seen as “nonessential” in this time of suddenly scarcer institutional resources.

One of the cherished ethical values in health care is autonomy, and in a deontological triage environment, honoring patient autonomy is carefully and tenderly administered. However, in a utilitarian-driven triage environment, considerations of the common good can trump autonomy, even in subtle ways that create inequities. Clinicians have been advised to have more frank conversations with patients, particularly those with chronic illnesses, stepping up initiatives to make advanced directives during this crisis, explicitly reminding patients that there may not be enough ventilators for all who need one.¹³ Some have argued that such physician-initiated conversations can be inherently coercive, making these decisions not as autonomous as it may appear, similar to physicians suggesting medical euthanasia as an option.¹⁴ Interestingly, some jurisdictions that offer euthanasia have been suspending such services during the COVID-19 crisis.¹⁵ Some hospitals have even wrestled with the possibility that all COVID-19 admissions should be considered “do not resuscitate,” especially because cardiopulmonary resuscitation significantly elevates the risks of viral exposure for the treatment team.^16,17 A more explicit example of how current standards protecting patient autonomy may be challenged is patients who are admitted involuntarily to a psychiatric unit. These are patients whose presumptively impaired autonomy is already being overridden by the involuntary nature of the admission. If a psychiatric unit requires admissions to be COVID-19–negative, and if patients refuse COVID-19 testing, should the testing be forced upon them to protect the entire milieu?

Many ethicists are highlighting the embedded equity bias known as “ableism” inherent in triage decisions—implicitly disfavoring resources for patients with COVID-19 who are already physically or intellectually disabled, chronically ill, aged, homeless, psychosocially low functioning, etc.¹⁸ Without explicit protections for individuals who are chronically disabled, triage decisions unguided by policy safeguards may reflexively favor the more “abled.” This bias towards the more abled is often inherent in how difficult it is to access health care. It can also be manifested in bedside triage decisions made in the moment by individual clinicians. Many disability rights advocates have been sounding this alarm during the COVID-19 crisis.¹⁹

Continue to: A special circumstance of equity...

A special circumstance of equity is arising during this ongoing pandemic—the possibility of treating health care workers as a privileged class. Unlike typical disasters, where health care workers come in afterwards, and therefore are in relatively less danger, pandemics create particularly high risks of danger for such individuals, with repeated exposure to the virus. They are both responders and potential victims. Should they have higher priority for ventilators, vaccines, funding, etc?⁶ This is a more robust degree of compensatory justice than merely giving appreciation. Giving health care workers such advantages may seem intuitively appealing, but perhaps professionalism and the self-obligation of duty mitigates such claims.²⁰

A unique opportunity

The magnitude and pervasiveness of this pandemic crisis is unique in our lifetimes, as both professionals and as citizens. In the crucible of this extraordinary time, these and other medical ethics dilemmas burn hotter than ever before. Different societies and institutions may come up with different answers, based on their cultures and values. It is important, however, that the venerable ethos of medical ethics, which has evolved through the millennia, codified in oaths, codes, and scholarship, can be a compass at the bedside and in the meetings of legislatures, leaders, and policymakers. Perhaps we can emerge from this time with more clarity about how to balance the preciousness of individual rights with the needs of the common good.

Bottom Line

The coronavirus disease 2019 (COVID-19) pandemic has brought increased attention to triage ethics and equity ethics. There is no coherent national or international agreement on how to best deploy limited supplies such as ventilators and personal protective equipment. Although the equitable distribution of health care delivery has long been a concern, this problem has become magnified by COVID-19. Clinicians may be asked to view health care through the less familiar lens of the common good, as opposed to focusing strictly on an individual patient.

Related Resources

• Johns Hopkins Berman Institute of Bioethics. Coronavirus ethics and policy insights and resources. https://bioethics.jhu.edu/research-and-outreach/covid-19-bioethics-expert-insights/.
• Daugherty-Biddison L, Gwon H, Regenberg A, et al. Maryland framework for the allocation of scarce lifesustaining medical resources in a catastrophic public health emergency. www.law.umaryland.edu/media/SOL/pdfs/Programs/Health-Law/MHECN/ASR%20Framework_Final.pdf.

It is clear that the coronavirus 2019 disease (COVID-19) pandemic is one of the most extraordinary epochs of our professional and personal lives. Besides the challenges to the techniques and technologies of care for this illness, we are seeing challenges to the fundamentals of health care, both to the systems whereby it is delivered, and to the ethical principles that guide that delivery. There is unprecedented relevance of certain ethical issues in the practice of medicine, many of which have previously been discussed in classrooms and textbooks, but now are at play in daily practice, particularly at the frontlines of the war against COVID-19.¹ In this article, I highlight several ethical dilemmas that are salient to these unique times. Some of the most compelling issues can be sorted into 2 clearly overlapping domains: triage ethics and equity ethics.

Triage ethics

In the areas most greatly affected by the COVID-19 pandemic, scarcity of treatment resources, such as ventilators, is a legitimate concern. French surgeon Dominique Jean Larry was the first to establish medical sorting protocols in the context of the battles of the Napoleonic wars, for which he used the French word triage, meaning “sorting.”² He articulated 3 prognostic categories: 1) those who would die even with treatment, 2) those who would live without treatment, and 3) those who would die unless treated. Triage decisions arise in the context of insufficient resources, particularly space, staff, and supplies. Although usually identified with disasters, these decisions can arise in other contexts where personnel or technological resources are inadequate. Indeed, one of the first modern incarnations of triage ethics in American civilian life was in the early days of hemodialysis, when so-called “God committees” made complex decisions about which patients would be able to use this new, rare technology.³

Two fundamental moral constructs undergird medical ethics: deontological and utilitarian. The former, in which most clinicians traffic in ordinary practice, is driven by principles or moral rules such as the sanctity of life, the rule of fairness, and the principle of autonomy.⁴ They apply primarily in the context of treating an individual patient. The utilitarian way of reasoning is not as familiar to clinicians. It is focused on the broader context, the common good, the health of the group. It asks to calculate “the greatest good for the greatest number” as a means of navigating ethical dilemmas.⁵ The utilitarian perspective is far more familiar to policymakers, health care administrators, and public health professionals. It tends to be anathema to clinicians. However, disasters such as the COVID-19 pandemic ask some clinicians, particularly inpatient physicians, to shift from their usual deontological perspective to a utilitarian one, because triage ethics fundamentally draw on utilitarian reasoning. This can be quite anguishing to clinicians who typically work with individual patients in settings of more adequate, if not abundant, resources. What may feel wrong in a deontological mode can be seen as ethically right in a utilitarian framework.

The Table compares and contrasts these 2 paradigms and how they manifest in the clinical trenches, in a protracted health care crisis with limited resources.

The COVID-19 crisis has produced an unprecedented and extended exposure of clinicians to triage situations in the face of limited resources such as ventilators, personnel, personal protective equipment, etc.⁶ Numerous possible approaches to deploying limited supplies are being considered. On what basis should such decisions be made? How can fairness be optimally manifest? Some possibilities include:

• first come, first served
• youngest first
• lottery
• short-term survivability
• long-term prognosis for quality of life
• value of a patient to the lives of others (eg, parents, health care workers, vaccine researchers).

One particularly interesting exploration of these questions was done in Maryland and reported in the “Maryland Framework for the Allocation of Scarce Life-sustaining Medical Resources in a Catastrophic Public Health Emergency.”⁷ This was the product of a multi-year consultation, ending in 2017, with several constituencies, including clinicians, politicians, hospital administrators, and members of the public brainstorming about approaches to allocating a hypothetical scarcity of ventilators. Interestingly, there was one broad consensus among these groups: a ventilator should not be withdrawn from a patient already using it to give to a “better” candidate who comes along later.

Some institutions have developed a method of making triage decisions that takes such decisions out of the hands of individual clinicians and instead assigns them to specialized “triage teams” made up of ethicists and clinicians experienced in critical care, to develop more distance from the emotions at the bedside. To minimize bias, such teams are often insulated from getting personal information about the patient, and receive only acute clinical information.⁸

Continue to: The pros and cons of these approaches...

The pros and cons of these approaches and the underlying ethical reasoning is beyond the scope of this overview. Policy documents from different states, regions, nations, and institutions have various approaches to making these choices. Presently, there is no coherent national or international agreement on triage ethics.⁹ It is important, however, that there be transparency in whatever approach an institution adopts for triage decisions.

Equity ethics

Though the equitable distribution of health care delivery has long been a concern, this problem has become magnified by the COVID-19 crisis. Race, sex, age, socioeconomic class, and type of illness have all been perennial sources of division between those who have better or worse access to health care and its outcomes. All of these distinctions have created differentials in rates of cases, hospitalizations, and deaths in the COVID-19 pandemic.¹⁰

The shifting of acute health care facilities to mostly COVID-19–related treatment, and postponing less critical and more “elective” care, creates a divide based on illness type. Many facilities have stopped taking admissions for other kinds of cases. This is particularly relevant to psychiatric units, many of which have had to decrease their bed capacities to make all rooms private, and limit their usual treatments offered to inpatients.¹¹ Many long-term units, such as at state hospitals, are closing to new admissions. Many day hospitals and intensive outpatient programs remain closed, not even shifting to telehealth. In areas most affected by COVID-19, some institutions have closed psychiatric wards and reallocated psychiatrists to cover some of the medical units. So the availability of the more intensive, institutionally-based levels of care is significantly reduced, particularly for psychiatric patients.¹² These patients already are a disadvantaged population in the distribution of health care resources, and the care of individuals with serious mental illness is more likely to be seen as “nonessential” in this time of suddenly scarcer institutional resources.

One of the cherished ethical values in health care is autonomy, and in a deontological triage environment, honoring patient autonomy is carefully and tenderly administered. However, in a utilitarian-driven triage environment, considerations of the common good can trump autonomy, even in subtle ways that create inequities. Clinicians have been advised to have more frank conversations with patients, particularly those with chronic illnesses, stepping up initiatives to make advanced directives during this crisis, explicitly reminding patients that there may not be enough ventilators for all who need one.¹³ Some have argued that such physician-initiated conversations can be inherently coercive, making these decisions not as autonomous as it may appear, similar to physicians suggesting medical euthanasia as an option.¹⁴ Interestingly, some jurisdictions that offer euthanasia have been suspending such services during the COVID-19 crisis.¹⁵ Some hospitals have even wrestled with the possibility that all COVID-19 admissions should be considered “do not resuscitate,” especially because cardiopulmonary resuscitation significantly elevates the risks of viral exposure for the treatment team.^16,17 A more explicit example of how current standards protecting patient autonomy may be challenged is patients who are admitted involuntarily to a psychiatric unit. These are patients whose presumptively impaired autonomy is already being overridden by the involuntary nature of the admission. If a psychiatric unit requires admissions to be COVID-19–negative, and if patients refuse COVID-19 testing, should the testing be forced upon them to protect the entire milieu?

Many ethicists are highlighting the embedded equity bias known as “ableism” inherent in triage decisions—implicitly disfavoring resources for patients with COVID-19 who are already physically or intellectually disabled, chronically ill, aged, homeless, psychosocially low functioning, etc.¹⁸ Without explicit protections for individuals who are chronically disabled, triage decisions unguided by policy safeguards may reflexively favor the more “abled.” This bias towards the more abled is often inherent in how difficult it is to access health care. It can also be manifested in bedside triage decisions made in the moment by individual clinicians. Many disability rights advocates have been sounding this alarm during the COVID-19 crisis.¹⁹

Continue to: A special circumstance of equity...

A special circumstance of equity is arising during this ongoing pandemic—the possibility of treating health care workers as a privileged class. Unlike typical disasters, where health care workers come in afterwards, and therefore are in relatively less danger, pandemics create particularly high risks of danger for such individuals, with repeated exposure to the virus. They are both responders and potential victims. Should they have higher priority for ventilators, vaccines, funding, etc?⁶ This is a more robust degree of compensatory justice than merely giving appreciation. Giving health care workers such advantages may seem intuitively appealing, but perhaps professionalism and the self-obligation of duty mitigates such claims.²⁰

A unique opportunity

The magnitude and pervasiveness of this pandemic crisis is unique in our lifetimes, as both professionals and as citizens. In the crucible of this extraordinary time, these and other medical ethics dilemmas burn hotter than ever before. Different societies and institutions may come up with different answers, based on their cultures and values. It is important, however, that the venerable ethos of medical ethics, which has evolved through the millennia, codified in oaths, codes, and scholarship, can be a compass at the bedside and in the meetings of legislatures, leaders, and policymakers. Perhaps we can emerge from this time with more clarity about how to balance the preciousness of individual rights with the needs of the common good.

Bottom Line

The coronavirus disease 2019 (COVID-19) pandemic has brought increased attention to triage ethics and equity ethics. There is no coherent national or international agreement on how to best deploy limited supplies such as ventilators and personal protective equipment. Although the equitable distribution of health care delivery has long been a concern, this problem has become magnified by COVID-19. Clinicians may be asked to view health care through the less familiar lens of the common good, as opposed to focusing strictly on an individual patient.

Related Resources

• Johns Hopkins Berman Institute of Bioethics. Coronavirus ethics and policy insights and resources. https://bioethics.jhu.edu/research-and-outreach/covid-19-bioethics-expert-insights/.
• Daugherty-Biddison L, Gwon H, Regenberg A, et al. Maryland framework for the allocation of scarce lifesustaining medical resources in a catastrophic public health emergency. www.law.umaryland.edu/media/SOL/pdfs/Programs/Health-Law/MHECN/ASR%20Framework_Final.pdf.

It is clear that the coronavirus 2019 disease (COVID-19) pandemic is one of the most extraordinary epochs of our professional and personal lives. Besides the challenges to the techniques and technologies of care for this illness, we are seeing challenges to the fundamentals of health care, both to the systems whereby it is delivered, and to the ethical principles that guide that delivery. There is unprecedented relevance of certain ethical issues in the practice of medicine, many of which have previously been discussed in classrooms and textbooks, but now are at play in daily practice, particularly at the frontlines of the war against COVID-19.¹ In this article, I highlight several ethical dilemmas that are salient to these unique times. Some of the most compelling issues can be sorted into 2 clearly overlapping domains: triage ethics and equity ethics.

Triage ethics

In the areas most greatly affected by the COVID-19 pandemic, scarcity of treatment resources, such as ventilators, is a legitimate concern. French surgeon Dominique Jean Larry was the first to establish medical sorting protocols in the context of the battles of the Napoleonic wars, for which he used the French word triage, meaning “sorting.”² He articulated 3 prognostic categories: 1) those who would die even with treatment, 2) those who would live without treatment, and 3) those who would die unless treated. Triage decisions arise in the context of insufficient resources, particularly space, staff, and supplies. Although usually identified with disasters, these decisions can arise in other contexts where personnel or technological resources are inadequate. Indeed, one of the first modern incarnations of triage ethics in American civilian life was in the early days of hemodialysis, when so-called “God committees” made complex decisions about which patients would be able to use this new, rare technology.³

Two fundamental moral constructs undergird medical ethics: deontological and utilitarian. The former, in which most clinicians traffic in ordinary practice, is driven by principles or moral rules such as the sanctity of life, the rule of fairness, and the principle of autonomy.⁴ They apply primarily in the context of treating an individual patient. The utilitarian way of reasoning is not as familiar to clinicians. It is focused on the broader context, the common good, the health of the group. It asks to calculate “the greatest good for the greatest number” as a means of navigating ethical dilemmas.⁵ The utilitarian perspective is far more familiar to policymakers, health care administrators, and public health professionals. It tends to be anathema to clinicians. However, disasters such as the COVID-19 pandemic ask some clinicians, particularly inpatient physicians, to shift from their usual deontological perspective to a utilitarian one, because triage ethics fundamentally draw on utilitarian reasoning. This can be quite anguishing to clinicians who typically work with individual patients in settings of more adequate, if not abundant, resources. What may feel wrong in a deontological mode can be seen as ethically right in a utilitarian framework.

The Table compares and contrasts these 2 paradigms and how they manifest in the clinical trenches, in a protracted health care crisis with limited resources.

The COVID-19 crisis has produced an unprecedented and extended exposure of clinicians to triage situations in the face of limited resources such as ventilators, personnel, personal protective equipment, etc.⁶ Numerous possible approaches to deploying limited supplies are being considered. On what basis should such decisions be made? How can fairness be optimally manifest? Some possibilities include:

• first come, first served
• youngest first
• lottery
• short-term survivability
• long-term prognosis for quality of life
• value of a patient to the lives of others (eg, parents, health care workers, vaccine researchers).

One particularly interesting exploration of these questions was done in Maryland and reported in the “Maryland Framework for the Allocation of Scarce Life-sustaining Medical Resources in a Catastrophic Public Health Emergency.”⁷ This was the product of a multi-year consultation, ending in 2017, with several constituencies, including clinicians, politicians, hospital administrators, and members of the public brainstorming about approaches to allocating a hypothetical scarcity of ventilators. Interestingly, there was one broad consensus among these groups: a ventilator should not be withdrawn from a patient already using it to give to a “better” candidate who comes along later.

Some institutions have developed a method of making triage decisions that takes such decisions out of the hands of individual clinicians and instead assigns them to specialized “triage teams” made up of ethicists and clinicians experienced in critical care, to develop more distance from the emotions at the bedside. To minimize bias, such teams are often insulated from getting personal information about the patient, and receive only acute clinical information.⁸

Continue to: The pros and cons of these approaches...

The pros and cons of these approaches and the underlying ethical reasoning is beyond the scope of this overview. Policy documents from different states, regions, nations, and institutions have various approaches to making these choices. Presently, there is no coherent national or international agreement on triage ethics.⁹ It is important, however, that there be transparency in whatever approach an institution adopts for triage decisions.

Equity ethics

Though the equitable distribution of health care delivery has long been a concern, this problem has become magnified by the COVID-19 crisis. Race, sex, age, socioeconomic class, and type of illness have all been perennial sources of division between those who have better or worse access to health care and its outcomes. All of these distinctions have created differentials in rates of cases, hospitalizations, and deaths in the COVID-19 pandemic.¹⁰

The shifting of acute health care facilities to mostly COVID-19–related treatment, and postponing less critical and more “elective” care, creates a divide based on illness type. Many facilities have stopped taking admissions for other kinds of cases. This is particularly relevant to psychiatric units, many of which have had to decrease their bed capacities to make all rooms private, and limit their usual treatments offered to inpatients.¹¹ Many long-term units, such as at state hospitals, are closing to new admissions. Many day hospitals and intensive outpatient programs remain closed, not even shifting to telehealth. In areas most affected by COVID-19, some institutions have closed psychiatric wards and reallocated psychiatrists to cover some of the medical units. So the availability of the more intensive, institutionally-based levels of care is significantly reduced, particularly for psychiatric patients.¹² These patients already are a disadvantaged population in the distribution of health care resources, and the care of individuals with serious mental illness is more likely to be seen as “nonessential” in this time of suddenly scarcer institutional resources.

One of the cherished ethical values in health care is autonomy, and in a deontological triage environment, honoring patient autonomy is carefully and tenderly administered. However, in a utilitarian-driven triage environment, considerations of the common good can trump autonomy, even in subtle ways that create inequities. Clinicians have been advised to have more frank conversations with patients, particularly those with chronic illnesses, stepping up initiatives to make advanced directives during this crisis, explicitly reminding patients that there may not be enough ventilators for all who need one.¹³ Some have argued that such physician-initiated conversations can be inherently coercive, making these decisions not as autonomous as it may appear, similar to physicians suggesting medical euthanasia as an option.¹⁴ Interestingly, some jurisdictions that offer euthanasia have been suspending such services during the COVID-19 crisis.¹⁵ Some hospitals have even wrestled with the possibility that all COVID-19 admissions should be considered “do not resuscitate,” especially because cardiopulmonary resuscitation significantly elevates the risks of viral exposure for the treatment team.^16,17 A more explicit example of how current standards protecting patient autonomy may be challenged is patients who are admitted involuntarily to a psychiatric unit. These are patients whose presumptively impaired autonomy is already being overridden by the involuntary nature of the admission. If a psychiatric unit requires admissions to be COVID-19–negative, and if patients refuse COVID-19 testing, should the testing be forced upon them to protect the entire milieu?

Many ethicists are highlighting the embedded equity bias known as “ableism” inherent in triage decisions—implicitly disfavoring resources for patients with COVID-19 who are already physically or intellectually disabled, chronically ill, aged, homeless, psychosocially low functioning, etc.¹⁸ Without explicit protections for individuals who are chronically disabled, triage decisions unguided by policy safeguards may reflexively favor the more “abled.” This bias towards the more abled is often inherent in how difficult it is to access health care. It can also be manifested in bedside triage decisions made in the moment by individual clinicians. Many disability rights advocates have been sounding this alarm during the COVID-19 crisis.¹⁹

Continue to: A special circumstance of equity...

A special circumstance of equity is arising during this ongoing pandemic—the possibility of treating health care workers as a privileged class. Unlike typical disasters, where health care workers come in afterwards, and therefore are in relatively less danger, pandemics create particularly high risks of danger for such individuals, with repeated exposure to the virus. They are both responders and potential victims. Should they have higher priority for ventilators, vaccines, funding, etc?⁶ This is a more robust degree of compensatory justice than merely giving appreciation. Giving health care workers such advantages may seem intuitively appealing, but perhaps professionalism and the self-obligation of duty mitigates such claims.²⁰

A unique opportunity

The magnitude and pervasiveness of this pandemic crisis is unique in our lifetimes, as both professionals and as citizens. In the crucible of this extraordinary time, these and other medical ethics dilemmas burn hotter than ever before. Different societies and institutions may come up with different answers, based on their cultures and values. It is important, however, that the venerable ethos of medical ethics, which has evolved through the millennia, codified in oaths, codes, and scholarship, can be a compass at the bedside and in the meetings of legislatures, leaders, and policymakers. Perhaps we can emerge from this time with more clarity about how to balance the preciousness of individual rights with the needs of the common good.

Bottom Line

The coronavirus disease 2019 (COVID-19) pandemic has brought increased attention to triage ethics and equity ethics. There is no coherent national or international agreement on how to best deploy limited supplies such as ventilators and personal protective equipment. Although the equitable distribution of health care delivery has long been a concern, this problem has become magnified by COVID-19. Clinicians may be asked to view health care through the less familiar lens of the common good, as opposed to focusing strictly on an individual patient.

Related Resources

• Johns Hopkins Berman Institute of Bioethics. Coronavirus ethics and policy insights and resources. https://bioethics.jhu.edu/research-and-outreach/covid-19-bioethics-expert-insights/.
• Daugherty-Biddison L, Gwon H, Regenberg A, et al. Maryland framework for the allocation of scarce lifesustaining medical resources in a catastrophic public health emergency. www.law.umaryland.edu/media/SOL/pdfs/Programs/Health-Law/MHECN/ASR%20Framework_Final.pdf.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non-COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no surgical masks only in confirmed COVID-19 patients or suspected cases; and reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room should be used for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Continue to practice standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area, minimizing the number of personnel in the room, avoiding change of personnel and keeping nonprocedural personnel out during the procedure, considering using nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non-COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no surgical masks only in confirmed COVID-19 patients or suspected cases; and reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room should be used for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Continue to practice standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area, minimizing the number of personnel in the room, avoiding change of personnel and keeping nonprocedural personnel out during the procedure, considering using nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non-COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no surgical masks only in confirmed COVID-19 patients or suspected cases; and reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room should be used for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Continue to practice standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area, minimizing the number of personnel in the room, avoiding change of personnel and keeping nonprocedural personnel out during the procedure, considering using nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.

“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.

She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.

No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.

The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.

“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.

Mitchel L. Zoler/MDedge News

The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.

“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.

Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
 

SELECT-PsA 1

In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.

The primary endpoint was an improvement of at least 20% (ACR20) at week 12.

Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.

Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.

Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).

More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.

The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”
 

SELECT-PsA 2

SELECT-PsA 2 compared upadacitinib – 15 mg or 30 mg once daily – with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.

The primary endpoint was the achievement of ACR20 at week 12.

Among the many secondary endpoints were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.

Adverse events were reported for patients who received at least one dose of upadacitinib.

At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs. 63.8% vs. 24.1%; P < .0001), as was ACR50 (31.8% vs. 37.6% vs. 4.1%; P < .0001) and ACR70 (8.5% vs. 16.5% vs. 0.5%; P < .0001). In addition, all secondary endpoints were significantly better with upadacitinib than with placebo.

Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.

“I was pleasantly surprised by the overall safety profile,” Dr. Mease said. “Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low.”

“We didn’t see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action,” he added.

Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.

“I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis,” he told Medscape Medical News. “I don’t think it’s going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients.”

Dr. Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn’t measured in these trials.

“I don’t see this as a weakness” of the current research, he said, but “having some spinal measures would be helpful. It’s something additional we’d like to know.”

Both trials were funded by AbbVie. Dr. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Dr. Mease reports financial relationships with Abbott, Amgen, Biogen, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Dr. Ritchlin has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.




 

Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.

“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.

She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.

No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.

The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.

“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.

Mitchel L. Zoler/MDedge News

The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.

“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.

Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
 

SELECT-PsA 1

In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.

The primary endpoint was an improvement of at least 20% (ACR20) at week 12.

Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.

Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.

Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).

More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.

The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”
 

SELECT-PsA 2

SELECT-PsA 2 compared upadacitinib – 15 mg or 30 mg once daily – with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.

The primary endpoint was the achievement of ACR20 at week 12.

Among the many secondary endpoints were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.

Adverse events were reported for patients who received at least one dose of upadacitinib.

At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs. 63.8% vs. 24.1%; P < .0001), as was ACR50 (31.8% vs. 37.6% vs. 4.1%; P < .0001) and ACR70 (8.5% vs. 16.5% vs. 0.5%; P < .0001). In addition, all secondary endpoints were significantly better with upadacitinib than with placebo.

Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.

“I was pleasantly surprised by the overall safety profile,” Dr. Mease said. “Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low.”

“We didn’t see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action,” he added.

Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.

“I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis,” he told Medscape Medical News. “I don’t think it’s going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients.”

Dr. Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn’t measured in these trials.

“I don’t see this as a weakness” of the current research, he said, but “having some spinal measures would be helpful. It’s something additional we’d like to know.”

Both trials were funded by AbbVie. Dr. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Dr. Mease reports financial relationships with Abbott, Amgen, Biogen, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Dr. Ritchlin has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.




 

Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.

“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.

She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.

No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.

The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.

“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.

Mitchel L. Zoler/MDedge News

The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.

“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.

Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
 

SELECT-PsA 1

In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.

The primary endpoint was an improvement of at least 20% (ACR20) at week 12.

Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.

Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.

Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).

More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.

The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”
 

SELECT-PsA 2

SELECT-PsA 2 compared upadacitinib – 15 mg or 30 mg once daily – with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.

The primary endpoint was the achievement of ACR20 at week 12.

Among the many secondary endpoints were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.

Adverse events were reported for patients who received at least one dose of upadacitinib.

At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs. 63.8% vs. 24.1%; P < .0001), as was ACR50 (31.8% vs. 37.6% vs. 4.1%; P < .0001) and ACR70 (8.5% vs. 16.5% vs. 0.5%; P < .0001). In addition, all secondary endpoints were significantly better with upadacitinib than with placebo.

Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.

“I was pleasantly surprised by the overall safety profile,” Dr. Mease said. “Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low.”

“We didn’t see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action,” he added.

Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.

“I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis,” he told Medscape Medical News. “I don’t think it’s going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients.”

Dr. Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn’t measured in these trials.

“I don’t see this as a weakness” of the current research, he said, but “having some spinal measures would be helpful. It’s something additional we’d like to know.”

Both trials were funded by AbbVie. Dr. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Dr. Mease reports financial relationships with Abbott, Amgen, Biogen, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Dr. Ritchlin has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.




 

Patients with rheumatoid arthritis remained on therapy longer with the relatively new JAK inhibitors than with TNF inhibitors, according to the large international JAK-pot study, offering encouraging signals about the efficacy and safety of JAK inhibitors in these patients.

“We saw that efficacy with JAK inhibitors was at least as good as other current drugs on the market,” said investigator Kim Lauper, MD, from the University of Geneva in Switzerland and the University of Manchester in the United Kingdom.

“We don’t have datasets on JAK inhibitors over a long period of time, but we do have a lot of registers,” Dr. Lauper told Medscape Medical News.

“In general, we were really happy to see no big difference in effectiveness” for these disease-modifying antirheumatic drugs (DMARDs) for patients with RA, she said.

In many countries, JAK inhibitors have only recently been approved as a treatment for RA, Lauper explained. In the past several years, baricitinib, tofacitinib, and upadacitinib have been approved by the U.S. Food and Drug Administration.

For their study, Dr. Lauper and her colleagues analyzed data from registers in 19 countries.

When JAK inhibitors became available in each country, the team assessed effectiveness by comparing how long patients remained on JAK inhibitors or on long-available biologics. Dr. Lauper presented the findings at the virtual European League Against Rheumatism (EULAR) 2020 Congress.

“In general, we know that drug retention is a measure of both effectiveness and safety,” she explained.

Of the 25,521 patients in the 19 registers, 6,063 started on a JAK inhibitor during the 3-year study period, 13,879 started on a TNF inhibitor, 2,348 started on abatacept, and 3,231 started on an interleukin-6 inhibitor.

Three-quarters of patients were women (average age, 55 years), and average time since the diagnosis of RA was 10 years.

At baseline, patients taking JAK inhibitors had higher levels of C-reactive protein and disease activity than patients taking a biologic. They had also been treated previously with more traditional and biologic DMARDs.

Ineffectiveness was the most common reason for discontinuing a drug, cited by 49% of patients, followed by adverse events, cited by 21%.

The rate of discontinuation was lower for JAK inhibitors than for TNF inhibitors, after adjustment. However, the discontinuation rate for JAK inhibitors, abatacept, and IL-6 inhibitors was comparable.

The observational nature of the study was a limitation, Dr. Lauper acknowledged, explaining that “we couldn’t adjust for confounding factors that were not measured.”

Notably, there were large variations in JAK inhibitor retention rates in the different countries, which surprised both Dr. Lauper and Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid.

“It’s very interesting because there’s not much heterogeneity with abatacept and IL inhibitors,” said Dr. Carmona, who is chair of the EULAR abstract selection committee.

“It’s all over the spectrum with JAK inhibitors,” she told Medscape Medical News. But “what the research shows is that JAK inhibitors are maintained for longer, which means maybe the mix of efficacy, low toxicity, and adherence, on the whole, is better in JAK inhibitors.”

The study was funded by Pfizer. Dr. Lauper and Dr. Carmona have disclosed no relevant financial relationships.

This story first appeared on Medscape.com.




 

Patients with rheumatoid arthritis remained on therapy longer with the relatively new JAK inhibitors than with TNF inhibitors, according to the large international JAK-pot study, offering encouraging signals about the efficacy and safety of JAK inhibitors in these patients.

“We saw that efficacy with JAK inhibitors was at least as good as other current drugs on the market,” said investigator Kim Lauper, MD, from the University of Geneva in Switzerland and the University of Manchester in the United Kingdom.

“We don’t have datasets on JAK inhibitors over a long period of time, but we do have a lot of registers,” Dr. Lauper told Medscape Medical News.

“In general, we were really happy to see no big difference in effectiveness” for these disease-modifying antirheumatic drugs (DMARDs) for patients with RA, she said.

In many countries, JAK inhibitors have only recently been approved as a treatment for RA, Lauper explained. In the past several years, baricitinib, tofacitinib, and upadacitinib have been approved by the U.S. Food and Drug Administration.

For their study, Dr. Lauper and her colleagues analyzed data from registers in 19 countries.

When JAK inhibitors became available in each country, the team assessed effectiveness by comparing how long patients remained on JAK inhibitors or on long-available biologics. Dr. Lauper presented the findings at the virtual European League Against Rheumatism (EULAR) 2020 Congress.

“In general, we know that drug retention is a measure of both effectiveness and safety,” she explained.

Of the 25,521 patients in the 19 registers, 6,063 started on a JAK inhibitor during the 3-year study period, 13,879 started on a TNF inhibitor, 2,348 started on abatacept, and 3,231 started on an interleukin-6 inhibitor.

Three-quarters of patients were women (average age, 55 years), and average time since the diagnosis of RA was 10 years.

At baseline, patients taking JAK inhibitors had higher levels of C-reactive protein and disease activity than patients taking a biologic. They had also been treated previously with more traditional and biologic DMARDs.

Ineffectiveness was the most common reason for discontinuing a drug, cited by 49% of patients, followed by adverse events, cited by 21%.

The rate of discontinuation was lower for JAK inhibitors than for TNF inhibitors, after adjustment. However, the discontinuation rate for JAK inhibitors, abatacept, and IL-6 inhibitors was comparable.

The observational nature of the study was a limitation, Dr. Lauper acknowledged, explaining that “we couldn’t adjust for confounding factors that were not measured.”

Notably, there were large variations in JAK inhibitor retention rates in the different countries, which surprised both Dr. Lauper and Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid.

“It’s very interesting because there’s not much heterogeneity with abatacept and IL inhibitors,” said Dr. Carmona, who is chair of the EULAR abstract selection committee.

“It’s all over the spectrum with JAK inhibitors,” she told Medscape Medical News. But “what the research shows is that JAK inhibitors are maintained for longer, which means maybe the mix of efficacy, low toxicity, and adherence, on the whole, is better in JAK inhibitors.”

The study was funded by Pfizer. Dr. Lauper and Dr. Carmona have disclosed no relevant financial relationships.

This story first appeared on Medscape.com.




 

Patients with rheumatoid arthritis remained on therapy longer with the relatively new JAK inhibitors than with TNF inhibitors, according to the large international JAK-pot study, offering encouraging signals about the efficacy and safety of JAK inhibitors in these patients.

“We saw that efficacy with JAK inhibitors was at least as good as other current drugs on the market,” said investigator Kim Lauper, MD, from the University of Geneva in Switzerland and the University of Manchester in the United Kingdom.

“We don’t have datasets on JAK inhibitors over a long period of time, but we do have a lot of registers,” Dr. Lauper told Medscape Medical News.

“In general, we were really happy to see no big difference in effectiveness” for these disease-modifying antirheumatic drugs (DMARDs) for patients with RA, she said.

In many countries, JAK inhibitors have only recently been approved as a treatment for RA, Lauper explained. In the past several years, baricitinib, tofacitinib, and upadacitinib have been approved by the U.S. Food and Drug Administration.

For their study, Dr. Lauper and her colleagues analyzed data from registers in 19 countries.

When JAK inhibitors became available in each country, the team assessed effectiveness by comparing how long patients remained on JAK inhibitors or on long-available biologics. Dr. Lauper presented the findings at the virtual European League Against Rheumatism (EULAR) 2020 Congress.

“In general, we know that drug retention is a measure of both effectiveness and safety,” she explained.

Of the 25,521 patients in the 19 registers, 6,063 started on a JAK inhibitor during the 3-year study period, 13,879 started on a TNF inhibitor, 2,348 started on abatacept, and 3,231 started on an interleukin-6 inhibitor.

Three-quarters of patients were women (average age, 55 years), and average time since the diagnosis of RA was 10 years.

At baseline, patients taking JAK inhibitors had higher levels of C-reactive protein and disease activity than patients taking a biologic. They had also been treated previously with more traditional and biologic DMARDs.

Ineffectiveness was the most common reason for discontinuing a drug, cited by 49% of patients, followed by adverse events, cited by 21%.

The rate of discontinuation was lower for JAK inhibitors than for TNF inhibitors, after adjustment. However, the discontinuation rate for JAK inhibitors, abatacept, and IL-6 inhibitors was comparable.

The observational nature of the study was a limitation, Dr. Lauper acknowledged, explaining that “we couldn’t adjust for confounding factors that were not measured.”

Notably, there were large variations in JAK inhibitor retention rates in the different countries, which surprised both Dr. Lauper and Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid.

“It’s very interesting because there’s not much heterogeneity with abatacept and IL inhibitors,” said Dr. Carmona, who is chair of the EULAR abstract selection committee.

“It’s all over the spectrum with JAK inhibitors,” she told Medscape Medical News. But “what the research shows is that JAK inhibitors are maintained for longer, which means maybe the mix of efficacy, low toxicity, and adherence, on the whole, is better in JAK inhibitors.”

The study was funded by Pfizer. Dr. Lauper and Dr. Carmona have disclosed no relevant financial relationships.

This story first appeared on Medscape.com.