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What psychiatrists can do to prepare for the coming pandemic
Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.
The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.
Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” – especially if you have parents in nursing homes.
The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?
For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.
Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.
A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.
For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.
The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.
COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.
Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.
Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.
The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.
Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” – especially if you have parents in nursing homes.
The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?
For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.
Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.
A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.
For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.
The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.
COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.
Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.
Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.
The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.
Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” – especially if you have parents in nursing homes.
The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?
For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.
Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.
A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.
For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.
The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.
COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.
Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.
HIV free 30 months after stem cell transplant, is the London patient cured?
A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.
The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.
After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.
The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.
In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?
“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.
In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.
In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.
Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.
In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.
Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.
The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.
The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.
The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.
Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.
The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.
Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.
“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.
Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.
As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.
The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”
Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”
Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,
SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.
A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.
The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.
After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.
The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.
In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?
“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.
In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.
In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.
Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.
In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.
Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.
The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.
The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.
The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.
Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.
The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.
Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.
“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.
Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.
As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.
The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”
Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”
Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,
SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.
A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.
The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.
After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.
The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.
In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?
“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.
In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.
In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.
Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.
In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.
Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.
The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.
The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.
The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.
Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.
The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.
Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.
“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.
Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.
As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.
The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”
Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”
Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,
SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.
FROM CROI 2020
Testosterone therapy linked to CV risk in men with HIV
Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.
There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.
Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.
The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.
Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.
The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.
In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.
About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.
Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.
The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.
SOURCE: Haberlen S et al. CROI 2020, Abstract 662.
Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.
There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.
Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.
The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.
Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.
The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.
In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.
About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.
Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.
The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.
SOURCE: Haberlen S et al. CROI 2020, Abstract 662.
Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.
There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.
Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.
The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.
Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.
The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.
In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.
About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.
Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.
The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.
SOURCE: Haberlen S et al. CROI 2020, Abstract 662.
FROM CROI 2020
In Memoriam
CHEST has been notified of the following deaths.
We extend our sincere condolences.
Nana Sunarya, MD (2019)
Michael Grant Ehrie Jr., MD (2019)
Robert F. Dunton, MD, FCCP (2020)
CHEST has been notified of the following deaths.
We extend our sincere condolences.
Nana Sunarya, MD (2019)
Michael Grant Ehrie Jr., MD (2019)
Robert F. Dunton, MD, FCCP (2020)
CHEST has been notified of the following deaths.
We extend our sincere condolences.
Nana Sunarya, MD (2019)
Michael Grant Ehrie Jr., MD (2019)
Robert F. Dunton, MD, FCCP (2020)
Disaster response. Medicare billing. Lung transplantation. Asthma.
Disaster response and global health
Corona virus and disaster preparedness campaign
On January 28, 2020, the US Centers for Disease Control and Prevention (CDC) issued a travel advisory recommending against all nonessential travel to China, in light of the 2019 novel coronavirus (2019-nCoV) outbreak.
Shortly thereafter, a plane that flew out of China was directed to land on a US air force base in California on Friday, January 31. Since then, other US government flights have evacuated patients to military bases throughout the country. The CDC issued a federal quarantine order lasting the 14-day incubation period to these repatriated US citizens. Nearby hospitals were debriefed and command centers set up in anticipation of any required intervention.
Initial diagnostic testing for 2019-nCoV could only be conducted at the CDC, but testing has recently become available at a larger number of laboratories via the CDC’s International Reagent Resource (IRR) network. Signs and symptoms that would warrant diagnostic testing include fever, cough, respiratory symptoms, shortness of breath, and breathing difficulties, in the context of travel to China within the prior 14 days or a high-risk contact with an ill patient. Severe cases can lead to pneumonia, kidney failure, severe acute respiratory distress, and death, with an in-hospital mortality of approximately 4% reported by clinicians in Wuhan, the epicenter of the outbreak (Wang D, et al. JAMA. Published online February 07, 2020. doi: 10.1001/jama.2020.1585).
The influenza vaccine will not protect against 2019-nCoV, and, currently, there is no available vaccine. The best prevention is to cover your mouth and nose with a tissue or your sleeve (not your hands) when coughing or sneezing. Surgical masks are not currently recommended as protection against 2019-nCoV. Hospitalized patients should be in negative-pressure rooms under respiratory and contact precautions, with gowns, gloves, eye protection, and either N95 masks or a powered air purifying respirator (PAPR) worn by clinical staff. Human-to human transmission is reported both within and outside of China (Rothe C, et al. N Engl J Med. Published online, Jan 30, 2020. doi: 10.1056/NEJMc2001468).
Clinical updates are available via the CDC at https://www.cdc.gov/coronavirus/2019-ncov/index.html. Clinicians are advised to check frequently, given the rapidly changing state of this epidemic.
John Agapian, MD, MS, FCCP
Steering Committee Member
Practice operations
New Medicare billing rules bring welcome documentation relief
At the end of 2019, the Centers for Medicare and Medicaid Services (CMS) released several changes to the Medicare Physician Fee Schedule, which will go into effect starting January 1, 2021. Though the adjustments are substantial (the document outlining the revisions is nearly 2,500 pages!), there are a few that deserve highlighting.
The most significant modification contained within the policy involves revisions to E/M codes for office visits. While the changes eliminate 99201, they preserve other graded levels for visits, with increases to the relative value units (RVUs) for most levels.
The most welcome changes for clinicians are twofold. First, billing no longer needs to be based on the maddening practice of trying to meet a minimum number of points from the history and exam. Clinicians can instead now bill based on time spent. The second refreshing modification is that time-based billing need no longer be solely face-to-face but can now be based on the realities of clinical practice today, ie, reviewing information and coordinating care with others.
Thus, these re-valued levels will allow outpatient physicians to bill based on time spent on things other than the office visit, such as time to review lab work and coordinate care with other specialties.
There will also be small changes to billing for pulmonary function testing, bronchoscopy (including the option for new indications for endobronchial valves), and for “brief communications via technology.” For a recap of these and other changes coming in January 2021, CHEST and ATS have produced a free webinar which is found online at: http://www.chestnet.org/Guidelines-and-Resources/Resources/Clinical-Practice-Resources.
Timothy Dempsey, MD, MPH
Steering Committee Fellow-in-Training
Deep Ramachandran, MD, FCCP
Steering Committee Member
Transplant
Investigating clinical practice of lung transplantation in systemic sclerosis
Interstitial lung disease (ILD) as a sequela of systemic sclerosis (SSc) poses a significant health concern. Patients with SSc-ILD experience symptoms of shortness of breath, reduced exercise capacity, and limited activities of daily living. Inducing fibrotic parenchymal change and pulmonary hypertension, SSc-ILD presents as both the most common extra-cutaneous manifestation and cause for mortality in this cohort (Mathai et al. Springer. 2014;139). Although rare, the prognosis of SSc-ILD is both difficult to understand and complex to manage.
With lung transplant being a treatment for end stage pulmonary disease, the role for lung transplantation in SSc-ILD is considered; however, remains controversial. Published literature exist without consensus. According to the recommendations of ISHLT, SSc is to be “carefully selected,” however, for some institutions, SSc remains a relative contraindication for lung transplant as definitive therapy (Weill et al. J Heart Lung Transplant. 2014;34[1]:1). Disease-specific concerns for SSc patients following lung transplant are esophageal dysmotility, dysphagia, gastroparesis, aspiration, and reflux disease. These comorbidities are associated with worsening prognosis in transplant survival (De Cruz, et al. Curr Opin Rheumatol. 2013;25[6]:714).
As clinical practices vary significantly in the management of SSc-ILD, we will survey transplant pulmonologist and surgeons from programs listed in Scientific Registry of Transplant Recipients (SRTR). We will evaluate transplant candidacy, preoperative transplant testing, postoperative transplant care, and outcomes. With this survey, we plan to determine the key practices of lung transplant programs regarding candidacy of patients with SSc-ILD perioperative management.
Clauden Louis, MD
Fellow-in-Training Member
Women’s lung health
Asthma and sex hormones
Overall asthma prevalence, severity, exacerbation rate, hospitalizations, and mortality are higher among women than men. Population studies show that asthma becomes more prevalent and severe in women following puberty, particularly in women with early menarche or multiple gestations. These findings suggest that sex hormones are important to the development and severity of asthma. Additional confounding variables include obesity, exposures, atopy, and age (Zien, et al. Curr Allergy Asthma Rep. 2015;15[6]:28).
Recent studies further define the gender disparity by detailing sex hormone differences in men and women with asthma. Han and colleagues recently reported on a cross-sectional study of serum-free testosterone and estradiol levels in over 7,000 adults in the National Health and Nutrition Examination Survey (NHANES, 2013-2016) (Han, et al. Am J Respir Crit Care Med. 2020;201[2]:158).
Elevated free testosterone levels were associated with lower odds of current asthma in women. After stratification for obesity, elevated free testosterone and estradiol levels were associated with reduced odds of current asthma in obese women, and elevated estradiol was associated with lower odds of asthma in non-obese men. It should be noted that increased luteal phase progesterone levels have also been implicated in increasing airway hyperresponsiveness (AHR) in asthmatics (Lipworth, et al. Am J Respir Crit Care Med. 2019; Oct 22, 2019).
In summary, testosterone is suggested to provide a protective, anti-inflammatory effect in women with asthma (Sathish, et al. Pharmacol Ther. 2015;150:94). Obesity interaction with sex hormones highlights its role as an important risk factor and disease modifier (Peters, et al. J Allergy Clin Immunol. 2018;141:1169). Future studies should continue to expand upon the role of sex hormones in relationship to multiple confounders. These insights will continue to define mechanisms that can be manipulated leading to novel pathway targeted therapies.
Candace Huebert, MD, FCCP
Margaret Pisani, MD, MPH, FCCP
Jill Poole, MD
Steering Committee Members
Disaster response and global health
Corona virus and disaster preparedness campaign
On January 28, 2020, the US Centers for Disease Control and Prevention (CDC) issued a travel advisory recommending against all nonessential travel to China, in light of the 2019 novel coronavirus (2019-nCoV) outbreak.
Shortly thereafter, a plane that flew out of China was directed to land on a US air force base in California on Friday, January 31. Since then, other US government flights have evacuated patients to military bases throughout the country. The CDC issued a federal quarantine order lasting the 14-day incubation period to these repatriated US citizens. Nearby hospitals were debriefed and command centers set up in anticipation of any required intervention.
Initial diagnostic testing for 2019-nCoV could only be conducted at the CDC, but testing has recently become available at a larger number of laboratories via the CDC’s International Reagent Resource (IRR) network. Signs and symptoms that would warrant diagnostic testing include fever, cough, respiratory symptoms, shortness of breath, and breathing difficulties, in the context of travel to China within the prior 14 days or a high-risk contact with an ill patient. Severe cases can lead to pneumonia, kidney failure, severe acute respiratory distress, and death, with an in-hospital mortality of approximately 4% reported by clinicians in Wuhan, the epicenter of the outbreak (Wang D, et al. JAMA. Published online February 07, 2020. doi: 10.1001/jama.2020.1585).
The influenza vaccine will not protect against 2019-nCoV, and, currently, there is no available vaccine. The best prevention is to cover your mouth and nose with a tissue or your sleeve (not your hands) when coughing or sneezing. Surgical masks are not currently recommended as protection against 2019-nCoV. Hospitalized patients should be in negative-pressure rooms under respiratory and contact precautions, with gowns, gloves, eye protection, and either N95 masks or a powered air purifying respirator (PAPR) worn by clinical staff. Human-to human transmission is reported both within and outside of China (Rothe C, et al. N Engl J Med. Published online, Jan 30, 2020. doi: 10.1056/NEJMc2001468).
Clinical updates are available via the CDC at https://www.cdc.gov/coronavirus/2019-ncov/index.html. Clinicians are advised to check frequently, given the rapidly changing state of this epidemic.
John Agapian, MD, MS, FCCP
Steering Committee Member
Practice operations
New Medicare billing rules bring welcome documentation relief
At the end of 2019, the Centers for Medicare and Medicaid Services (CMS) released several changes to the Medicare Physician Fee Schedule, which will go into effect starting January 1, 2021. Though the adjustments are substantial (the document outlining the revisions is nearly 2,500 pages!), there are a few that deserve highlighting.
The most significant modification contained within the policy involves revisions to E/M codes for office visits. While the changes eliminate 99201, they preserve other graded levels for visits, with increases to the relative value units (RVUs) for most levels.
The most welcome changes for clinicians are twofold. First, billing no longer needs to be based on the maddening practice of trying to meet a minimum number of points from the history and exam. Clinicians can instead now bill based on time spent. The second refreshing modification is that time-based billing need no longer be solely face-to-face but can now be based on the realities of clinical practice today, ie, reviewing information and coordinating care with others.
Thus, these re-valued levels will allow outpatient physicians to bill based on time spent on things other than the office visit, such as time to review lab work and coordinate care with other specialties.
There will also be small changes to billing for pulmonary function testing, bronchoscopy (including the option for new indications for endobronchial valves), and for “brief communications via technology.” For a recap of these and other changes coming in January 2021, CHEST and ATS have produced a free webinar which is found online at: http://www.chestnet.org/Guidelines-and-Resources/Resources/Clinical-Practice-Resources.
Timothy Dempsey, MD, MPH
Steering Committee Fellow-in-Training
Deep Ramachandran, MD, FCCP
Steering Committee Member
Transplant
Investigating clinical practice of lung transplantation in systemic sclerosis
Interstitial lung disease (ILD) as a sequela of systemic sclerosis (SSc) poses a significant health concern. Patients with SSc-ILD experience symptoms of shortness of breath, reduced exercise capacity, and limited activities of daily living. Inducing fibrotic parenchymal change and pulmonary hypertension, SSc-ILD presents as both the most common extra-cutaneous manifestation and cause for mortality in this cohort (Mathai et al. Springer. 2014;139). Although rare, the prognosis of SSc-ILD is both difficult to understand and complex to manage.
With lung transplant being a treatment for end stage pulmonary disease, the role for lung transplantation in SSc-ILD is considered; however, remains controversial. Published literature exist without consensus. According to the recommendations of ISHLT, SSc is to be “carefully selected,” however, for some institutions, SSc remains a relative contraindication for lung transplant as definitive therapy (Weill et al. J Heart Lung Transplant. 2014;34[1]:1). Disease-specific concerns for SSc patients following lung transplant are esophageal dysmotility, dysphagia, gastroparesis, aspiration, and reflux disease. These comorbidities are associated with worsening prognosis in transplant survival (De Cruz, et al. Curr Opin Rheumatol. 2013;25[6]:714).
As clinical practices vary significantly in the management of SSc-ILD, we will survey transplant pulmonologist and surgeons from programs listed in Scientific Registry of Transplant Recipients (SRTR). We will evaluate transplant candidacy, preoperative transplant testing, postoperative transplant care, and outcomes. With this survey, we plan to determine the key practices of lung transplant programs regarding candidacy of patients with SSc-ILD perioperative management.
Clauden Louis, MD
Fellow-in-Training Member
Women’s lung health
Asthma and sex hormones
Overall asthma prevalence, severity, exacerbation rate, hospitalizations, and mortality are higher among women than men. Population studies show that asthma becomes more prevalent and severe in women following puberty, particularly in women with early menarche or multiple gestations. These findings suggest that sex hormones are important to the development and severity of asthma. Additional confounding variables include obesity, exposures, atopy, and age (Zien, et al. Curr Allergy Asthma Rep. 2015;15[6]:28).
Recent studies further define the gender disparity by detailing sex hormone differences in men and women with asthma. Han and colleagues recently reported on a cross-sectional study of serum-free testosterone and estradiol levels in over 7,000 adults in the National Health and Nutrition Examination Survey (NHANES, 2013-2016) (Han, et al. Am J Respir Crit Care Med. 2020;201[2]:158).
Elevated free testosterone levels were associated with lower odds of current asthma in women. After stratification for obesity, elevated free testosterone and estradiol levels were associated with reduced odds of current asthma in obese women, and elevated estradiol was associated with lower odds of asthma in non-obese men. It should be noted that increased luteal phase progesterone levels have also been implicated in increasing airway hyperresponsiveness (AHR) in asthmatics (Lipworth, et al. Am J Respir Crit Care Med. 2019; Oct 22, 2019).
In summary, testosterone is suggested to provide a protective, anti-inflammatory effect in women with asthma (Sathish, et al. Pharmacol Ther. 2015;150:94). Obesity interaction with sex hormones highlights its role as an important risk factor and disease modifier (Peters, et al. J Allergy Clin Immunol. 2018;141:1169). Future studies should continue to expand upon the role of sex hormones in relationship to multiple confounders. These insights will continue to define mechanisms that can be manipulated leading to novel pathway targeted therapies.
Candace Huebert, MD, FCCP
Margaret Pisani, MD, MPH, FCCP
Jill Poole, MD
Steering Committee Members
Disaster response and global health
Corona virus and disaster preparedness campaign
On January 28, 2020, the US Centers for Disease Control and Prevention (CDC) issued a travel advisory recommending against all nonessential travel to China, in light of the 2019 novel coronavirus (2019-nCoV) outbreak.
Shortly thereafter, a plane that flew out of China was directed to land on a US air force base in California on Friday, January 31. Since then, other US government flights have evacuated patients to military bases throughout the country. The CDC issued a federal quarantine order lasting the 14-day incubation period to these repatriated US citizens. Nearby hospitals were debriefed and command centers set up in anticipation of any required intervention.
Initial diagnostic testing for 2019-nCoV could only be conducted at the CDC, but testing has recently become available at a larger number of laboratories via the CDC’s International Reagent Resource (IRR) network. Signs and symptoms that would warrant diagnostic testing include fever, cough, respiratory symptoms, shortness of breath, and breathing difficulties, in the context of travel to China within the prior 14 days or a high-risk contact with an ill patient. Severe cases can lead to pneumonia, kidney failure, severe acute respiratory distress, and death, with an in-hospital mortality of approximately 4% reported by clinicians in Wuhan, the epicenter of the outbreak (Wang D, et al. JAMA. Published online February 07, 2020. doi: 10.1001/jama.2020.1585).
The influenza vaccine will not protect against 2019-nCoV, and, currently, there is no available vaccine. The best prevention is to cover your mouth and nose with a tissue or your sleeve (not your hands) when coughing or sneezing. Surgical masks are not currently recommended as protection against 2019-nCoV. Hospitalized patients should be in negative-pressure rooms under respiratory and contact precautions, with gowns, gloves, eye protection, and either N95 masks or a powered air purifying respirator (PAPR) worn by clinical staff. Human-to human transmission is reported both within and outside of China (Rothe C, et al. N Engl J Med. Published online, Jan 30, 2020. doi: 10.1056/NEJMc2001468).
Clinical updates are available via the CDC at https://www.cdc.gov/coronavirus/2019-ncov/index.html. Clinicians are advised to check frequently, given the rapidly changing state of this epidemic.
John Agapian, MD, MS, FCCP
Steering Committee Member
Practice operations
New Medicare billing rules bring welcome documentation relief
At the end of 2019, the Centers for Medicare and Medicaid Services (CMS) released several changes to the Medicare Physician Fee Schedule, which will go into effect starting January 1, 2021. Though the adjustments are substantial (the document outlining the revisions is nearly 2,500 pages!), there are a few that deserve highlighting.
The most significant modification contained within the policy involves revisions to E/M codes for office visits. While the changes eliminate 99201, they preserve other graded levels for visits, with increases to the relative value units (RVUs) for most levels.
The most welcome changes for clinicians are twofold. First, billing no longer needs to be based on the maddening practice of trying to meet a minimum number of points from the history and exam. Clinicians can instead now bill based on time spent. The second refreshing modification is that time-based billing need no longer be solely face-to-face but can now be based on the realities of clinical practice today, ie, reviewing information and coordinating care with others.
Thus, these re-valued levels will allow outpatient physicians to bill based on time spent on things other than the office visit, such as time to review lab work and coordinate care with other specialties.
There will also be small changes to billing for pulmonary function testing, bronchoscopy (including the option for new indications for endobronchial valves), and for “brief communications via technology.” For a recap of these and other changes coming in January 2021, CHEST and ATS have produced a free webinar which is found online at: http://www.chestnet.org/Guidelines-and-Resources/Resources/Clinical-Practice-Resources.
Timothy Dempsey, MD, MPH
Steering Committee Fellow-in-Training
Deep Ramachandran, MD, FCCP
Steering Committee Member
Transplant
Investigating clinical practice of lung transplantation in systemic sclerosis
Interstitial lung disease (ILD) as a sequela of systemic sclerosis (SSc) poses a significant health concern. Patients with SSc-ILD experience symptoms of shortness of breath, reduced exercise capacity, and limited activities of daily living. Inducing fibrotic parenchymal change and pulmonary hypertension, SSc-ILD presents as both the most common extra-cutaneous manifestation and cause for mortality in this cohort (Mathai et al. Springer. 2014;139). Although rare, the prognosis of SSc-ILD is both difficult to understand and complex to manage.
With lung transplant being a treatment for end stage pulmonary disease, the role for lung transplantation in SSc-ILD is considered; however, remains controversial. Published literature exist without consensus. According to the recommendations of ISHLT, SSc is to be “carefully selected,” however, for some institutions, SSc remains a relative contraindication for lung transplant as definitive therapy (Weill et al. J Heart Lung Transplant. 2014;34[1]:1). Disease-specific concerns for SSc patients following lung transplant are esophageal dysmotility, dysphagia, gastroparesis, aspiration, and reflux disease. These comorbidities are associated with worsening prognosis in transplant survival (De Cruz, et al. Curr Opin Rheumatol. 2013;25[6]:714).
As clinical practices vary significantly in the management of SSc-ILD, we will survey transplant pulmonologist and surgeons from programs listed in Scientific Registry of Transplant Recipients (SRTR). We will evaluate transplant candidacy, preoperative transplant testing, postoperative transplant care, and outcomes. With this survey, we plan to determine the key practices of lung transplant programs regarding candidacy of patients with SSc-ILD perioperative management.
Clauden Louis, MD
Fellow-in-Training Member
Women’s lung health
Asthma and sex hormones
Overall asthma prevalence, severity, exacerbation rate, hospitalizations, and mortality are higher among women than men. Population studies show that asthma becomes more prevalent and severe in women following puberty, particularly in women with early menarche or multiple gestations. These findings suggest that sex hormones are important to the development and severity of asthma. Additional confounding variables include obesity, exposures, atopy, and age (Zien, et al. Curr Allergy Asthma Rep. 2015;15[6]:28).
Recent studies further define the gender disparity by detailing sex hormone differences in men and women with asthma. Han and colleagues recently reported on a cross-sectional study of serum-free testosterone and estradiol levels in over 7,000 adults in the National Health and Nutrition Examination Survey (NHANES, 2013-2016) (Han, et al. Am J Respir Crit Care Med. 2020;201[2]:158).
Elevated free testosterone levels were associated with lower odds of current asthma in women. After stratification for obesity, elevated free testosterone and estradiol levels were associated with reduced odds of current asthma in obese women, and elevated estradiol was associated with lower odds of asthma in non-obese men. It should be noted that increased luteal phase progesterone levels have also been implicated in increasing airway hyperresponsiveness (AHR) in asthmatics (Lipworth, et al. Am J Respir Crit Care Med. 2019; Oct 22, 2019).
In summary, testosterone is suggested to provide a protective, anti-inflammatory effect in women with asthma (Sathish, et al. Pharmacol Ther. 2015;150:94). Obesity interaction with sex hormones highlights its role as an important risk factor and disease modifier (Peters, et al. J Allergy Clin Immunol. 2018;141:1169). Future studies should continue to expand upon the role of sex hormones in relationship to multiple confounders. These insights will continue to define mechanisms that can be manipulated leading to novel pathway targeted therapies.
Candace Huebert, MD, FCCP
Margaret Pisani, MD, MPH, FCCP
Jill Poole, MD
Steering Committee Members
Meet the FISH Bowl Finalists
CHEST 2019 marked the inaugural FISH Bowl competition for attendees. Inspired by Shark Tank, our kinder, gentler, yet still competitive and cutting-edge FISH Bowl (Furthering Innovation and Science for Health) featured CHEST members disrupting our beliefs about how clinical care and education are performed. As health-care providers, they presented innovative ideas pertaining to education and clinical disease for pulmonary, critical care, and sleep medicine. Six finalists were chosen from dozens of submissions, and three emerged winners. In this new Meet the FISH Bowl Finalists series, CHEST introduces you to many of them – including Clinical Disease Category Winner Dr. Gao.
Name: Catherine Gao, MD
Institutional Affiliation: Northwestern University
Position: Pulmonary & Critical Care Fellow
Title: Time to Vent: A Blended Learning Experience
Brief Summary: It is difficult for ventilated patients to communicate, and this is cited by patients as one of the most stressful parts of their ICU stays. Brain-computer interface technology allows for communication to happen directly from brain wave activity and represents a potential tool to fix this problem.
1. What inspired your innovation? Every clinician has had the frustrating experience of difficulty communicating with their ventilated patients, and it is even more challenging for patients and their families. I read about recent advances in communication methods from the neurology literature and thought about expanding this technology to the ICU.
2. What do you see as challenges to your innovation gaining widespread acceptance? How can they be overcome? This is still an early idea with technology still being developed – there have been investments by the military and large tech companies, as well as universities – it will take time for the technology to be ready for clinical use, and there will be troubleshooting needed as with all new technologies.
3. What impact has winning FISH Bowl 2019 had on your vision for the innovation? The judges gave great feedback and had wonderful suggestions and questions. This is just the beginning.
4. How do you think your success at FISH Bowl 2019 will continue to impact your career overall in the months and years to come? This was a great experience to talk about interesting ideas, and I had the opportunity to talk to many people with similar interests after the presentation. I thank CHEST for this amazing opportunity and look forward to the years to come!
CHEST 2019 marked the inaugural FISH Bowl competition for attendees. Inspired by Shark Tank, our kinder, gentler, yet still competitive and cutting-edge FISH Bowl (Furthering Innovation and Science for Health) featured CHEST members disrupting our beliefs about how clinical care and education are performed. As health-care providers, they presented innovative ideas pertaining to education and clinical disease for pulmonary, critical care, and sleep medicine. Six finalists were chosen from dozens of submissions, and three emerged winners. In this new Meet the FISH Bowl Finalists series, CHEST introduces you to many of them – including Clinical Disease Category Winner Dr. Gao.
Name: Catherine Gao, MD
Institutional Affiliation: Northwestern University
Position: Pulmonary & Critical Care Fellow
Title: Time to Vent: A Blended Learning Experience
Brief Summary: It is difficult for ventilated patients to communicate, and this is cited by patients as one of the most stressful parts of their ICU stays. Brain-computer interface technology allows for communication to happen directly from brain wave activity and represents a potential tool to fix this problem.
1. What inspired your innovation? Every clinician has had the frustrating experience of difficulty communicating with their ventilated patients, and it is even more challenging for patients and their families. I read about recent advances in communication methods from the neurology literature and thought about expanding this technology to the ICU.
2. What do you see as challenges to your innovation gaining widespread acceptance? How can they be overcome? This is still an early idea with technology still being developed – there have been investments by the military and large tech companies, as well as universities – it will take time for the technology to be ready for clinical use, and there will be troubleshooting needed as with all new technologies.
3. What impact has winning FISH Bowl 2019 had on your vision for the innovation? The judges gave great feedback and had wonderful suggestions and questions. This is just the beginning.
4. How do you think your success at FISH Bowl 2019 will continue to impact your career overall in the months and years to come? This was a great experience to talk about interesting ideas, and I had the opportunity to talk to many people with similar interests after the presentation. I thank CHEST for this amazing opportunity and look forward to the years to come!
CHEST 2019 marked the inaugural FISH Bowl competition for attendees. Inspired by Shark Tank, our kinder, gentler, yet still competitive and cutting-edge FISH Bowl (Furthering Innovation and Science for Health) featured CHEST members disrupting our beliefs about how clinical care and education are performed. As health-care providers, they presented innovative ideas pertaining to education and clinical disease for pulmonary, critical care, and sleep medicine. Six finalists were chosen from dozens of submissions, and three emerged winners. In this new Meet the FISH Bowl Finalists series, CHEST introduces you to many of them – including Clinical Disease Category Winner Dr. Gao.
Name: Catherine Gao, MD
Institutional Affiliation: Northwestern University
Position: Pulmonary & Critical Care Fellow
Title: Time to Vent: A Blended Learning Experience
Brief Summary: It is difficult for ventilated patients to communicate, and this is cited by patients as one of the most stressful parts of their ICU stays. Brain-computer interface technology allows for communication to happen directly from brain wave activity and represents a potential tool to fix this problem.
1. What inspired your innovation? Every clinician has had the frustrating experience of difficulty communicating with their ventilated patients, and it is even more challenging for patients and their families. I read about recent advances in communication methods from the neurology literature and thought about expanding this technology to the ICU.
2. What do you see as challenges to your innovation gaining widespread acceptance? How can they be overcome? This is still an early idea with technology still being developed – there have been investments by the military and large tech companies, as well as universities – it will take time for the technology to be ready for clinical use, and there will be troubleshooting needed as with all new technologies.
3. What impact has winning FISH Bowl 2019 had on your vision for the innovation? The judges gave great feedback and had wonderful suggestions and questions. This is just the beginning.
4. How do you think your success at FISH Bowl 2019 will continue to impact your career overall in the months and years to come? This was a great experience to talk about interesting ideas, and I had the opportunity to talk to many people with similar interests after the presentation. I thank CHEST for this amazing opportunity and look forward to the years to come!
Cultivating resilience against nurse burnout
From AACN Bold Voices
Developing resilient nurses and work environments can help organizations prevent burnout.
The Joint Commission released an advisory urging health-care organizations to promote resilience as a way to combat and prevent nurse burnout.
“Developing resilience to combat nurse burnout,” in The Joint Commission’s Quick Safety newsletter, notes that 15.6% of all nurses in a survey of more than 2,000 healthcare partners reported experiencing burnout “with emergency room nurses being at a higher risk,” which can affect the physical and emotional health of staff, as well as patient safety, mortality, and satisfaction.
According to data presented in the article, omitting nurses from the decision-making process, security risks, a need for more autonomy, and staffing challenges are the most common factors associated with nurse burnout.
To promote resilience in nurses and in the work environment, which can help prevent and reduce burnout among nurses and other front-line staff, health-care organizations should consider a number of strategies, including the following:
• Teach nurses and nurse leaders the elements of resilience, such as empowerment and colleague support, and how to identify symptoms of burnout.
• Provide positive role models and mentors.
• “Engage nursing input in staff meetings by posting an agenda and asking for additional items the nurses would like to discuss or present.”
• Measure the well-being of health-care providers; try interventions and then assess their effectiveness.
The article also notes that “mindfulness and resilience training alone cannot effectively address burnout unless the leadership is simultaneously reducing and eliminating barriers and impediments to nursing workflow, such as staffing and workplace environment concerns.”
Reference
The Joint Commission. Developing resilience to combat nurse burnout. Quick Safety. 2019;(50):1-4.
From AACN Bold Voices
From AACN Bold Voices
Developing resilient nurses and work environments can help organizations prevent burnout.
The Joint Commission released an advisory urging health-care organizations to promote resilience as a way to combat and prevent nurse burnout.
“Developing resilience to combat nurse burnout,” in The Joint Commission’s Quick Safety newsletter, notes that 15.6% of all nurses in a survey of more than 2,000 healthcare partners reported experiencing burnout “with emergency room nurses being at a higher risk,” which can affect the physical and emotional health of staff, as well as patient safety, mortality, and satisfaction.
According to data presented in the article, omitting nurses from the decision-making process, security risks, a need for more autonomy, and staffing challenges are the most common factors associated with nurse burnout.
To promote resilience in nurses and in the work environment, which can help prevent and reduce burnout among nurses and other front-line staff, health-care organizations should consider a number of strategies, including the following:
• Teach nurses and nurse leaders the elements of resilience, such as empowerment and colleague support, and how to identify symptoms of burnout.
• Provide positive role models and mentors.
• “Engage nursing input in staff meetings by posting an agenda and asking for additional items the nurses would like to discuss or present.”
• Measure the well-being of health-care providers; try interventions and then assess their effectiveness.
The article also notes that “mindfulness and resilience training alone cannot effectively address burnout unless the leadership is simultaneously reducing and eliminating barriers and impediments to nursing workflow, such as staffing and workplace environment concerns.”
Reference
The Joint Commission. Developing resilience to combat nurse burnout. Quick Safety. 2019;(50):1-4.
Developing resilient nurses and work environments can help organizations prevent burnout.
The Joint Commission released an advisory urging health-care organizations to promote resilience as a way to combat and prevent nurse burnout.
“Developing resilience to combat nurse burnout,” in The Joint Commission’s Quick Safety newsletter, notes that 15.6% of all nurses in a survey of more than 2,000 healthcare partners reported experiencing burnout “with emergency room nurses being at a higher risk,” which can affect the physical and emotional health of staff, as well as patient safety, mortality, and satisfaction.
According to data presented in the article, omitting nurses from the decision-making process, security risks, a need for more autonomy, and staffing challenges are the most common factors associated with nurse burnout.
To promote resilience in nurses and in the work environment, which can help prevent and reduce burnout among nurses and other front-line staff, health-care organizations should consider a number of strategies, including the following:
• Teach nurses and nurse leaders the elements of resilience, such as empowerment and colleague support, and how to identify symptoms of burnout.
• Provide positive role models and mentors.
• “Engage nursing input in staff meetings by posting an agenda and asking for additional items the nurses would like to discuss or present.”
• Measure the well-being of health-care providers; try interventions and then assess their effectiveness.
The article also notes that “mindfulness and resilience training alone cannot effectively address burnout unless the leadership is simultaneously reducing and eliminating barriers and impediments to nursing workflow, such as staffing and workplace environment concerns.”
Reference
The Joint Commission. Developing resilience to combat nurse burnout. Quick Safety. 2019;(50):1-4.
This month in the journal CHEST®
Editor’s Picks
Original Research
Safety and Effectiveness of Bronchial Thermoplasty When FEV1 Is Less Than 50%.
By Dr. D. Langton, et al.
Utilization and Outcomes of Thrombolytic Therapy for Acute Pulmonary Embolism: A Nationwide Cohort Study.
By S. E. Beyer, et al.
An Individualized Prediction Model for Long-term Lung Function Trajectory and Risk of COPD in the General Population.
By Dr. W. Chen, et al.
CHEST Review
Six-Minute Walk Test: Clinical Role, Technique, Coding, and Reimbursement.
By Dr. P. Agarwala, et al.
How I Do It
An Algorithmic Approach to the Interpretation of Diffuse Lung Disease on Chest CT Imaging: A Theory of Almost Everything.
By Dr. J. F. Gruden, et al.
Editor’s Picks
Editor’s Picks
Original Research
Safety and Effectiveness of Bronchial Thermoplasty When FEV1 Is Less Than 50%.
By Dr. D. Langton, et al.
Utilization and Outcomes of Thrombolytic Therapy for Acute Pulmonary Embolism: A Nationwide Cohort Study.
By S. E. Beyer, et al.
An Individualized Prediction Model for Long-term Lung Function Trajectory and Risk of COPD in the General Population.
By Dr. W. Chen, et al.
CHEST Review
Six-Minute Walk Test: Clinical Role, Technique, Coding, and Reimbursement.
By Dr. P. Agarwala, et al.
How I Do It
An Algorithmic Approach to the Interpretation of Diffuse Lung Disease on Chest CT Imaging: A Theory of Almost Everything.
By Dr. J. F. Gruden, et al.
Original Research
Safety and Effectiveness of Bronchial Thermoplasty When FEV1 Is Less Than 50%.
By Dr. D. Langton, et al.
Utilization and Outcomes of Thrombolytic Therapy for Acute Pulmonary Embolism: A Nationwide Cohort Study.
By S. E. Beyer, et al.
An Individualized Prediction Model for Long-term Lung Function Trajectory and Risk of COPD in the General Population.
By Dr. W. Chen, et al.
CHEST Review
Six-Minute Walk Test: Clinical Role, Technique, Coding, and Reimbursement.
By Dr. P. Agarwala, et al.
How I Do It
An Algorithmic Approach to the Interpretation of Diffuse Lung Disease on Chest CT Imaging: A Theory of Almost Everything.
By Dr. J. F. Gruden, et al.
Descovy safety no match for cost savings with generic Truvada, study says
Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.
Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.
Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.
FROM CROI 2020
Advances in ankylosing spondylitis hailed as rheumatology’s story of the year
MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.
“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.
“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.
“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.
“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”
Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.
“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.
In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.
“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.
Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).
Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
More biologics coming for nr-AxSpA
In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.
Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.
ACR/SAA/SPARTAN guidelines critiqued
The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.
“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.
Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.
“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.
He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.
“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.
Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.
“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.
Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.
MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.
“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.
“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.
“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.
“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”
Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.
“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.
In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.
“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.
Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).
Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
More biologics coming for nr-AxSpA
In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.
Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.
ACR/SAA/SPARTAN guidelines critiqued
The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.
“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.
Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.
“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.
He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.
“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.
Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.
“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.
Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.
MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.
“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.
“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.
“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.
“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”
Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.
“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.
In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.
“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.
Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).
Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
More biologics coming for nr-AxSpA
In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.
Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.
ACR/SAA/SPARTAN guidelines critiqued
The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.
“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.
Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.
“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.
He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.
“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.
Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.
“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.
Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.
REPORTING FROM RWCS 2020