The recently published PIONEER-HF study attempts to move sacubitril/valsartan (Entresto) therapy to the inpatient environment to improve patient and physician acceptance of this therapy for patients with heart failure (N Engl J Med. 2019 Feb 7;380;539-48).

When given to outpatients in the PARADIGM-HF trial, the combination was superior to enalapril for reducing the risks of death and hospitalization for heart failure (N Engl J Med 2014;371:993-1004.) Specifically, sacubitril/valsartan decreased mortality by 15% and hospitalization by 21% as an outpatient therapy for patients with systolic heart failure. Nevertheless, there has not been widespread adoption of this approach. It is well known that physicians can be slow to adopt new therapies, but one overriding factor may be the cost of the drug compared to enalapril, one of the first drugs shown to be effective in heart failure therapy (Entresto costs more than $4,000 per year; enalapril costs about $120 per year).

The investigators in the PIONEER-HF study compared Entresto to enalapril over a 2-month period in patients hospitalized with systolic heart failure. To accelerate the trial, the investigators used the proportional change in patients’ N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as the primary endpoint rather than the traditional outcome of morbidity and mortality. In the short term, no significant clinical benefits were observed, but there was a significant decrease in NT-proBNP of about 30% (P less than .001).

The investigators suggested that this finding extended the previous benefit observed with Entresto during outpatient initiation and could be used as a rationale for initiating Entresto therapy in the hospital. This earlier application of the therapy could make the drug more widely acceptable.

Considerable investigation in BNP measurement has occurred over the last few years, and although it is clear that BNP is elevated in heart failure patients, there is no evidence to confirm that the decrease in BNP is associated with improved outcome. BNP will fall with decrease in ventricular volume, which may have significant physiologic mechanisms but ventricular volume could decrease with fall in blood pressure that may have occurred in this population since hypotension tended to be more frequent with Entresto than with enalapril. The traditional measure of heart failure benefit with beta-blockers, ACE inhibitors, and aldosterone antagonists in the inpatient and early postdischarge period has depended on clinical outcomes.

Regardless of the physiologic explanation of this fall in BNP, we must pause in our assumptions when a surrogate measure is used to assess clinical benefit as inpatient therapy. The Food and Drug Administration has long given up using surrogate measures as proof of efficacy, and rightly so. Clinical medicine is replete with dubious drug benefits based on surrogate measures. Let’s not forget that only a few years ago suppression of premature ventricular contractions was considered to be a measure of the pharmacologic prevention of sudden death. We have come a long way from that and other clinical missteps to use BNP, an uncertain marker at best of clinical improvement, as a surrogate for the improvement in heart failure.

There is a substantial amount of data supporting the benefit of Entresto in the clinical management of outpatients with heart failure without using the PIONEER-HF trial results as a pretense to initiate therapy when patients are hospitalized. One might suggest that if Novartis is concerned about introducing the drug in the clinical management of heart failure, the company might consider the possibility of decreasing its price.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

The recently published PIONEER-HF study attempts to move sacubitril/valsartan (Entresto) therapy to the inpatient environment to improve patient and physician acceptance of this therapy for patients with heart failure (N Engl J Med. 2019 Feb 7;380;539-48).

When given to outpatients in the PARADIGM-HF trial, the combination was superior to enalapril for reducing the risks of death and hospitalization for heart failure (N Engl J Med 2014;371:993-1004.) Specifically, sacubitril/valsartan decreased mortality by 15% and hospitalization by 21% as an outpatient therapy for patients with systolic heart failure. Nevertheless, there has not been widespread adoption of this approach. It is well known that physicians can be slow to adopt new therapies, but one overriding factor may be the cost of the drug compared to enalapril, one of the first drugs shown to be effective in heart failure therapy (Entresto costs more than $4,000 per year; enalapril costs about $120 per year).

The investigators in the PIONEER-HF study compared Entresto to enalapril over a 2-month period in patients hospitalized with systolic heart failure. To accelerate the trial, the investigators used the proportional change in patients’ N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as the primary endpoint rather than the traditional outcome of morbidity and mortality. In the short term, no significant clinical benefits were observed, but there was a significant decrease in NT-proBNP of about 30% (P less than .001).

The investigators suggested that this finding extended the previous benefit observed with Entresto during outpatient initiation and could be used as a rationale for initiating Entresto therapy in the hospital. This earlier application of the therapy could make the drug more widely acceptable.

Considerable investigation in BNP measurement has occurred over the last few years, and although it is clear that BNP is elevated in heart failure patients, there is no evidence to confirm that the decrease in BNP is associated with improved outcome. BNP will fall with decrease in ventricular volume, which may have significant physiologic mechanisms but ventricular volume could decrease with fall in blood pressure that may have occurred in this population since hypotension tended to be more frequent with Entresto than with enalapril. The traditional measure of heart failure benefit with beta-blockers, ACE inhibitors, and aldosterone antagonists in the inpatient and early postdischarge period has depended on clinical outcomes.

Regardless of the physiologic explanation of this fall in BNP, we must pause in our assumptions when a surrogate measure is used to assess clinical benefit as inpatient therapy. The Food and Drug Administration has long given up using surrogate measures as proof of efficacy, and rightly so. Clinical medicine is replete with dubious drug benefits based on surrogate measures. Let’s not forget that only a few years ago suppression of premature ventricular contractions was considered to be a measure of the pharmacologic prevention of sudden death. We have come a long way from that and other clinical missteps to use BNP, an uncertain marker at best of clinical improvement, as a surrogate for the improvement in heart failure.

There is a substantial amount of data supporting the benefit of Entresto in the clinical management of outpatients with heart failure without using the PIONEER-HF trial results as a pretense to initiate therapy when patients are hospitalized. One might suggest that if Novartis is concerned about introducing the drug in the clinical management of heart failure, the company might consider the possibility of decreasing its price.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

The recently published PIONEER-HF study attempts to move sacubitril/valsartan (Entresto) therapy to the inpatient environment to improve patient and physician acceptance of this therapy for patients with heart failure (N Engl J Med. 2019 Feb 7;380;539-48).

When given to outpatients in the PARADIGM-HF trial, the combination was superior to enalapril for reducing the risks of death and hospitalization for heart failure (N Engl J Med 2014;371:993-1004.) Specifically, sacubitril/valsartan decreased mortality by 15% and hospitalization by 21% as an outpatient therapy for patients with systolic heart failure. Nevertheless, there has not been widespread adoption of this approach. It is well known that physicians can be slow to adopt new therapies, but one overriding factor may be the cost of the drug compared to enalapril, one of the first drugs shown to be effective in heart failure therapy (Entresto costs more than $4,000 per year; enalapril costs about $120 per year).

The investigators in the PIONEER-HF study compared Entresto to enalapril over a 2-month period in patients hospitalized with systolic heart failure. To accelerate the trial, the investigators used the proportional change in patients’ N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as the primary endpoint rather than the traditional outcome of morbidity and mortality. In the short term, no significant clinical benefits were observed, but there was a significant decrease in NT-proBNP of about 30% (P less than .001).

The investigators suggested that this finding extended the previous benefit observed with Entresto during outpatient initiation and could be used as a rationale for initiating Entresto therapy in the hospital. This earlier application of the therapy could make the drug more widely acceptable.

Considerable investigation in BNP measurement has occurred over the last few years, and although it is clear that BNP is elevated in heart failure patients, there is no evidence to confirm that the decrease in BNP is associated with improved outcome. BNP will fall with decrease in ventricular volume, which may have significant physiologic mechanisms but ventricular volume could decrease with fall in blood pressure that may have occurred in this population since hypotension tended to be more frequent with Entresto than with enalapril. The traditional measure of heart failure benefit with beta-blockers, ACE inhibitors, and aldosterone antagonists in the inpatient and early postdischarge period has depended on clinical outcomes.

Regardless of the physiologic explanation of this fall in BNP, we must pause in our assumptions when a surrogate measure is used to assess clinical benefit as inpatient therapy. The Food and Drug Administration has long given up using surrogate measures as proof of efficacy, and rightly so. Clinical medicine is replete with dubious drug benefits based on surrogate measures. Let’s not forget that only a few years ago suppression of premature ventricular contractions was considered to be a measure of the pharmacologic prevention of sudden death. We have come a long way from that and other clinical missteps to use BNP, an uncertain marker at best of clinical improvement, as a surrogate for the improvement in heart failure.

There is a substantial amount of data supporting the benefit of Entresto in the clinical management of outpatients with heart failure without using the PIONEER-HF trial results as a pretense to initiate therapy when patients are hospitalized. One might suggest that if Novartis is concerned about introducing the drug in the clinical management of heart failure, the company might consider the possibility of decreasing its price.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

LAKE BUENA VISTA, FLA. – Patient-reported outcomes (PROs) have the potential to transform patient care in rheumatology, according to Jeffrey Curtis, MD.

Courtesy UAB Photo

“You probably already use a lot of PROs in your data; even if you measure nothing via a questionnaire, you are still collecting it in a qualitative way – you just might not call it that,” he told attendees at the annual meeting of the Florida Society of Rheumatology.

The key to making the most of PROs is efficient collection of relevant, interpretable, actionable data for improving patient care and outcomes, said Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.
 

PROs: The “what” and “why”

A wide variety of tools are available to capture PROs during daily practice, Dr. Curtis said. Active data capture tools include rheumatology- or domain-specific measures such as the Bath Ankylosing Spondylitis Disease Activity and Functional Indices (BASDAI and BASFI), the Routine Assessment of Patient Index Data 3 (RAPID3), the original and Multidimensional Health Assessment Questionnaires (HAQ and MDHAQ), as well as disease-agnostic measures like the 36-item Short Form Survey (SF-36), EuroQol-5D (EQ-5D), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, he explained, adding that passive data also can be derived from various sources, including social media platforms, activity trackers, and reports regarding balance and falls, sleep quality and duration, heart rate and rhythm, and galvanic skin resistance.

Many of these measures represent things patients can track at home between office visits, he said.

However, such measures represent “what we could have” in terms of patient data, whereas “what we do have” falls far short of that, he noted, citing a study in which he and his colleagues found that the use of quantitative measurement for U.S. rheumatoid arthritis (RA) patients is increasing over time, but remains low with only 58% of 439 rheumatologists who responded to an email survey reporting use of such measures (J Rheumatol. 2018;45[1]:40-4).

Those using the measures were more likely to be in group practice and to prescribe tumor necrosis factor inhibitors, and the tools they reported using most often were the HAQ (35.5%) and RAPID3 (27.1%).

Reasons given for not using quantitative measurement included time constraints and electronic availability.

Of note, simulated case scenarios included in the study demonstrated that providing more quantitative information increased the likelihood that a patient would change to a different disease-modifying antirheumatic drug or biologic.

Almost anything clinically relevant can be quantified, but it’s really hard to improve and address problems you’re not measuring, Dr. Curtis said.

“I would contend that PROs are an important part of holistic rheumatology care, and they absolutely impact real and perceived treatment responses,” he added.

In fact, in a study presented at the 2018 European League Against Rheumatism Congress, he and his colleagues found that PROMIS scores with respect to pain interference, sleep disturbance, and fatigue tracked closely with RA patients’ view of their health status and with Clinical Disease Activity Index (CDAI) scores.
 

PROs: The “how”

“Is it merely enough to collect patient data? Is that going to solve the problem? Well, probably not – it really needs to be actionable,” he said. “Outcomes don’t get better by themselves; you really need to be collecting data that you, personally, will find valuable for your patients, and ideally it needs to mean something to patients.”

Many of these suggestions are potentially actionable, he noted.

“You can download these forms on paper; this is already connected or connectable to some people’s electronic health record,” he said. “At a minimum, talk to your EHR vendor about whether this might be available, and if not, why not.”

Choose in-office tools that are quick and simple to use, he advised, noting that he finds 6-8 minutes ideal for patient completion of questionnaires and other measures.

“It’s quite reasonable to write a PRO order,” he said. “The notion would be that you decide what specific PROs you want Mrs. Smith to give you, how often you’d like for her to tell you about those things (what you want from her might be different from the next patient), and she can give you that data from a smartphone or maybe something that she wears, and only the data that you asked for comes back.”

Successful collection of such data requires patient engagement in the process, he said, noting that the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB was recently awarded a grant to help develop an arthritis research registry called Arthritis Power, through which patients can provide data via smartphones, track their own health outcomes, participate in studies and surveys, access educational tools, and receive reminders and feedback.

“One of the things that’s quite important to help engage patients is to encourage them. This isn’t one-way data transfer,” he said.

Keeping them engaged requires “contributive science messaging.” That is, telling them they are “part of something bigger [and that they are] helping answer research questions that patients care about.”

It also helps to “bring back value to them” by explaining that you can help them make their data useful for improving their health and that you can derive insights for or with them based on their data.

“You can ‘game-ify’ it and make it fun,” he said, adding that leveraging the social connections associated with some tools can also help.

However, the promise of better access to needed resources, physicians, and the health care system is perhaps the most compelling point for patient engagement, he said.

“[You can say] to your patient, ‘Mrs. Smith, I’d really like to have your Fitbit or Apple Watch data, and I’d like you to tell me how you’re doing, on your smartphone, once or twice a month – it will take about 10 minutes – because I, as your doctor, think I can take better care of you,’ ” he said. “If that’s the ask, I think that might be the most compelling reason for patients to say yes.”

Of note, a number of patient measures are now compensable, Dr. Curtis said, mentioning depression screening using a PROMIS instrument as one example.

Additionally, two American College of Rheumatology work groups are revising the ACR recommendations on functional status measures and will soon generate an “ACR-approved list” of measures, he said.

He stressed, however, that it in addition to understanding the value of specific tools, it is important to know their limitations.

In the PREDICT study, he and his colleagues demonstrated that patient-reported RAPID3 data, when compared with investigator-based CDAI data for assessing RA patients’ response to certolizumab at 12 weeks and predicting response at 52 weeks, resulted in 11.9% fewer patients being classified as responders (64.7% vs. 76.4%), but the actual response rates at week 52 were similar, with 31.5% and 32.3% of patients in the groups, respectively, achieving a low level of disease activity (Arthritis Rheumatol. 2015;67[12]:3104-12).

The concern regarding the finding is that an insurance company may refuse to continue paying for a drug because of the perceived lack of response and thereby unnecessarily force a switch to an alternate drug based on faulty data, he explained.

“That would be the real-world analog of what this trial evaluated,” he said, adding that this has important implications for treat-to-target, pay-for-performance, and merit-based incentive payment systems. “My point is that we need to know the limitations of our tools ... and it’s to not let insurance [companies] write rules for us ... based upon certain tools that have limitations.”

Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Patient-reported outcomes (PROs) have the potential to transform patient care in rheumatology, according to Jeffrey Curtis, MD.

Courtesy UAB Photo

“You probably already use a lot of PROs in your data; even if you measure nothing via a questionnaire, you are still collecting it in a qualitative way – you just might not call it that,” he told attendees at the annual meeting of the Florida Society of Rheumatology.

The key to making the most of PROs is efficient collection of relevant, interpretable, actionable data for improving patient care and outcomes, said Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.
 

PROs: The “what” and “why”

A wide variety of tools are available to capture PROs during daily practice, Dr. Curtis said. Active data capture tools include rheumatology- or domain-specific measures such as the Bath Ankylosing Spondylitis Disease Activity and Functional Indices (BASDAI and BASFI), the Routine Assessment of Patient Index Data 3 (RAPID3), the original and Multidimensional Health Assessment Questionnaires (HAQ and MDHAQ), as well as disease-agnostic measures like the 36-item Short Form Survey (SF-36), EuroQol-5D (EQ-5D), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, he explained, adding that passive data also can be derived from various sources, including social media platforms, activity trackers, and reports regarding balance and falls, sleep quality and duration, heart rate and rhythm, and galvanic skin resistance.

Many of these measures represent things patients can track at home between office visits, he said.

However, such measures represent “what we could have” in terms of patient data, whereas “what we do have” falls far short of that, he noted, citing a study in which he and his colleagues found that the use of quantitative measurement for U.S. rheumatoid arthritis (RA) patients is increasing over time, but remains low with only 58% of 439 rheumatologists who responded to an email survey reporting use of such measures (J Rheumatol. 2018;45[1]:40-4).

Those using the measures were more likely to be in group practice and to prescribe tumor necrosis factor inhibitors, and the tools they reported using most often were the HAQ (35.5%) and RAPID3 (27.1%).

Reasons given for not using quantitative measurement included time constraints and electronic availability.

Of note, simulated case scenarios included in the study demonstrated that providing more quantitative information increased the likelihood that a patient would change to a different disease-modifying antirheumatic drug or biologic.

Almost anything clinically relevant can be quantified, but it’s really hard to improve and address problems you’re not measuring, Dr. Curtis said.

“I would contend that PROs are an important part of holistic rheumatology care, and they absolutely impact real and perceived treatment responses,” he added.

In fact, in a study presented at the 2018 European League Against Rheumatism Congress, he and his colleagues found that PROMIS scores with respect to pain interference, sleep disturbance, and fatigue tracked closely with RA patients’ view of their health status and with Clinical Disease Activity Index (CDAI) scores.
 

PROs: The “how”

“Is it merely enough to collect patient data? Is that going to solve the problem? Well, probably not – it really needs to be actionable,” he said. “Outcomes don’t get better by themselves; you really need to be collecting data that you, personally, will find valuable for your patients, and ideally it needs to mean something to patients.”

Many of these suggestions are potentially actionable, he noted.

“You can download these forms on paper; this is already connected or connectable to some people’s electronic health record,” he said. “At a minimum, talk to your EHR vendor about whether this might be available, and if not, why not.”

Choose in-office tools that are quick and simple to use, he advised, noting that he finds 6-8 minutes ideal for patient completion of questionnaires and other measures.

“It’s quite reasonable to write a PRO order,” he said. “The notion would be that you decide what specific PROs you want Mrs. Smith to give you, how often you’d like for her to tell you about those things (what you want from her might be different from the next patient), and she can give you that data from a smartphone or maybe something that she wears, and only the data that you asked for comes back.”

Successful collection of such data requires patient engagement in the process, he said, noting that the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB was recently awarded a grant to help develop an arthritis research registry called Arthritis Power, through which patients can provide data via smartphones, track their own health outcomes, participate in studies and surveys, access educational tools, and receive reminders and feedback.

“One of the things that’s quite important to help engage patients is to encourage them. This isn’t one-way data transfer,” he said.

Keeping them engaged requires “contributive science messaging.” That is, telling them they are “part of something bigger [and that they are] helping answer research questions that patients care about.”

It also helps to “bring back value to them” by explaining that you can help them make their data useful for improving their health and that you can derive insights for or with them based on their data.

“You can ‘game-ify’ it and make it fun,” he said, adding that leveraging the social connections associated with some tools can also help.

However, the promise of better access to needed resources, physicians, and the health care system is perhaps the most compelling point for patient engagement, he said.

“[You can say] to your patient, ‘Mrs. Smith, I’d really like to have your Fitbit or Apple Watch data, and I’d like you to tell me how you’re doing, on your smartphone, once or twice a month – it will take about 10 minutes – because I, as your doctor, think I can take better care of you,’ ” he said. “If that’s the ask, I think that might be the most compelling reason for patients to say yes.”

Of note, a number of patient measures are now compensable, Dr. Curtis said, mentioning depression screening using a PROMIS instrument as one example.

Additionally, two American College of Rheumatology work groups are revising the ACR recommendations on functional status measures and will soon generate an “ACR-approved list” of measures, he said.

He stressed, however, that it in addition to understanding the value of specific tools, it is important to know their limitations.

In the PREDICT study, he and his colleagues demonstrated that patient-reported RAPID3 data, when compared with investigator-based CDAI data for assessing RA patients’ response to certolizumab at 12 weeks and predicting response at 52 weeks, resulted in 11.9% fewer patients being classified as responders (64.7% vs. 76.4%), but the actual response rates at week 52 were similar, with 31.5% and 32.3% of patients in the groups, respectively, achieving a low level of disease activity (Arthritis Rheumatol. 2015;67[12]:3104-12).

The concern regarding the finding is that an insurance company may refuse to continue paying for a drug because of the perceived lack of response and thereby unnecessarily force a switch to an alternate drug based on faulty data, he explained.

“That would be the real-world analog of what this trial evaluated,” he said, adding that this has important implications for treat-to-target, pay-for-performance, and merit-based incentive payment systems. “My point is that we need to know the limitations of our tools ... and it’s to not let insurance [companies] write rules for us ... based upon certain tools that have limitations.”

Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Patient-reported outcomes (PROs) have the potential to transform patient care in rheumatology, according to Jeffrey Curtis, MD.

Courtesy UAB Photo

“You probably already use a lot of PROs in your data; even if you measure nothing via a questionnaire, you are still collecting it in a qualitative way – you just might not call it that,” he told attendees at the annual meeting of the Florida Society of Rheumatology.

The key to making the most of PROs is efficient collection of relevant, interpretable, actionable data for improving patient care and outcomes, said Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.
 

PROs: The “what” and “why”

A wide variety of tools are available to capture PROs during daily practice, Dr. Curtis said. Active data capture tools include rheumatology- or domain-specific measures such as the Bath Ankylosing Spondylitis Disease Activity and Functional Indices (BASDAI and BASFI), the Routine Assessment of Patient Index Data 3 (RAPID3), the original and Multidimensional Health Assessment Questionnaires (HAQ and MDHAQ), as well as disease-agnostic measures like the 36-item Short Form Survey (SF-36), EuroQol-5D (EQ-5D), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, he explained, adding that passive data also can be derived from various sources, including social media platforms, activity trackers, and reports regarding balance and falls, sleep quality and duration, heart rate and rhythm, and galvanic skin resistance.

Many of these measures represent things patients can track at home between office visits, he said.

However, such measures represent “what we could have” in terms of patient data, whereas “what we do have” falls far short of that, he noted, citing a study in which he and his colleagues found that the use of quantitative measurement for U.S. rheumatoid arthritis (RA) patients is increasing over time, but remains low with only 58% of 439 rheumatologists who responded to an email survey reporting use of such measures (J Rheumatol. 2018;45[1]:40-4).

Those using the measures were more likely to be in group practice and to prescribe tumor necrosis factor inhibitors, and the tools they reported using most often were the HAQ (35.5%) and RAPID3 (27.1%).

Reasons given for not using quantitative measurement included time constraints and electronic availability.

Of note, simulated case scenarios included in the study demonstrated that providing more quantitative information increased the likelihood that a patient would change to a different disease-modifying antirheumatic drug or biologic.

Almost anything clinically relevant can be quantified, but it’s really hard to improve and address problems you’re not measuring, Dr. Curtis said.

“I would contend that PROs are an important part of holistic rheumatology care, and they absolutely impact real and perceived treatment responses,” he added.

In fact, in a study presented at the 2018 European League Against Rheumatism Congress, he and his colleagues found that PROMIS scores with respect to pain interference, sleep disturbance, and fatigue tracked closely with RA patients’ view of their health status and with Clinical Disease Activity Index (CDAI) scores.
 

PROs: The “how”

“Is it merely enough to collect patient data? Is that going to solve the problem? Well, probably not – it really needs to be actionable,” he said. “Outcomes don’t get better by themselves; you really need to be collecting data that you, personally, will find valuable for your patients, and ideally it needs to mean something to patients.”

Many of these suggestions are potentially actionable, he noted.

“You can download these forms on paper; this is already connected or connectable to some people’s electronic health record,” he said. “At a minimum, talk to your EHR vendor about whether this might be available, and if not, why not.”

Choose in-office tools that are quick and simple to use, he advised, noting that he finds 6-8 minutes ideal for patient completion of questionnaires and other measures.

“It’s quite reasonable to write a PRO order,” he said. “The notion would be that you decide what specific PROs you want Mrs. Smith to give you, how often you’d like for her to tell you about those things (what you want from her might be different from the next patient), and she can give you that data from a smartphone or maybe something that she wears, and only the data that you asked for comes back.”

Successful collection of such data requires patient engagement in the process, he said, noting that the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB was recently awarded a grant to help develop an arthritis research registry called Arthritis Power, through which patients can provide data via smartphones, track their own health outcomes, participate in studies and surveys, access educational tools, and receive reminders and feedback.

“One of the things that’s quite important to help engage patients is to encourage them. This isn’t one-way data transfer,” he said.

Keeping them engaged requires “contributive science messaging.” That is, telling them they are “part of something bigger [and that they are] helping answer research questions that patients care about.”

It also helps to “bring back value to them” by explaining that you can help them make their data useful for improving their health and that you can derive insights for or with them based on their data.

“You can ‘game-ify’ it and make it fun,” he said, adding that leveraging the social connections associated with some tools can also help.

However, the promise of better access to needed resources, physicians, and the health care system is perhaps the most compelling point for patient engagement, he said.

“[You can say] to your patient, ‘Mrs. Smith, I’d really like to have your Fitbit or Apple Watch data, and I’d like you to tell me how you’re doing, on your smartphone, once or twice a month – it will take about 10 minutes – because I, as your doctor, think I can take better care of you,’ ” he said. “If that’s the ask, I think that might be the most compelling reason for patients to say yes.”

Of note, a number of patient measures are now compensable, Dr. Curtis said, mentioning depression screening using a PROMIS instrument as one example.

Additionally, two American College of Rheumatology work groups are revising the ACR recommendations on functional status measures and will soon generate an “ACR-approved list” of measures, he said.

He stressed, however, that it in addition to understanding the value of specific tools, it is important to know their limitations.

In the PREDICT study, he and his colleagues demonstrated that patient-reported RAPID3 data, when compared with investigator-based CDAI data for assessing RA patients’ response to certolizumab at 12 weeks and predicting response at 52 weeks, resulted in 11.9% fewer patients being classified as responders (64.7% vs. 76.4%), but the actual response rates at week 52 were similar, with 31.5% and 32.3% of patients in the groups, respectively, achieving a low level of disease activity (Arthritis Rheumatol. 2015;67[12]:3104-12).

The concern regarding the finding is that an insurance company may refuse to continue paying for a drug because of the perceived lack of response and thereby unnecessarily force a switch to an alternate drug based on faulty data, he explained.

“That would be the real-world analog of what this trial evaluated,” he said, adding that this has important implications for treat-to-target, pay-for-performance, and merit-based incentive payment systems. “My point is that we need to know the limitations of our tools ... and it’s to not let insurance [companies] write rules for us ... based upon certain tools that have limitations.”

Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Rheumatologists comprise a “tiny sliver” of the U.S. physician pie chart, but their voices are nevertheless being heard and making a difference regarding policies that affect the specialty, according to Angus B. Worthing, MD.

However, given the myriad policy issues on the table, more and louder voices are needed, he said at the annual meeting of the Florida Society of Rheumatology, where, as chair of the American College of Rheumatology’s Government Affairs Committee, he provided an “advocacy update” on the committee’s activities.

Recent ACR “wins” as outlined by Dr. Worthing include:

• The postponement and modification of proposed cuts to Evaluation & Management (E/M) current procedural terminology (CPT) codes.

“Last summer, Medicare proposed that instead of having low-complexity to high-complexity E/M codes, they would condense all of the doctor visits into one code, which would obviously enhance the reimbursement for low complexity, but ding and penalize the reimbursement for high-complexity visits like ours,” said Dr. Worthing, who also is a partner in a private rheumatology practice in the Washington area.

An ACR press release on the proposal led to pivotal coverage of the issue in the New York Times. “It looks like not only did they postpone those cuts, they modified [the proposal], and we’ll find out any day now in the proposal for the next year’s physician fee schedule whether they’ll scrap it entirely and instead try to plus-up E/M code reimbursement for complex patients.”

• The elimination of proposed Merit-based Incentive Payment System (MIPS) adjustments on Medicare drug reimbursement.

A cut to fee-for-service reimbursement for drug costs as a MIPS penalty could have quickly bankrupted rheumatology practices, Dr. Worthing said.

“[The success] was largely out of rheumatologists and others saying that this could quickly stop access to these treatments, because we wouldn’t be able to provide them,” he noted.

• The dampening of proposed musculoskeletal ultrasound reimbursement cuts in Medicare.

Ultrasound is a safe, effective, dynamic, and relatively low-cost diagnostic tool, but Medicare has been considering “absurd” cuts to reimbursement, Dr. Worthing said.

“We’ve been able to have good conversations with Medicare ... to bring that argument to Medicare, and we’ll find out – again, when the physician fee schedule comes out – whether they’ll continue the plan to cut diagnostic ultrasound reimbursement or whether they’ll stop cutting it.”

• The inclusion of more favorable Medicare Advantage regulations for step therapy “grandfathering.”

Medicare Advantage plans were given the chance last summer to use step therapy in Part B medicines for the first time.

“The ACR quickly told the executive branch and officials at [the Department of Health & Human Services (HHS)], that this would not be good for our patients getting medications,” Dr. Worthing said.

Going forward with that plan, and looking back just 108 days to allow people to stay on their medications – as was proposed – wouldn’t work, as some drugs are dosed every 4-6 months, or every year or every 2 years, he said.

“The look of astonishment on the [HHS] deputy secretary’s face when I told him that there was a drug in the U.S. that you give every 2 years was helpful for me to know that these people really need to hear from us before they issue these kinds of regulations,” he said.

The administration listened to the rheumatologists and is going to look back 365 days to keep people on their drugs, he said.

The ACR took the lead on these recent successes, but was also involved in a number of other wins achieved through multisociety efforts, he said.

Examples include securing a $2 billion increase in National Institutes of Health funding, eliminating “gag clauses” that prevent pharmacists from informing patients when it’s cheaper to just buy a drug rather than using their insurance; getting rid of annual caps on physical and other rehabilitation therapy for patients meeting their targets; repealing (before it could take effect) of the Independent Payment Advisory Board established by the Affordable Care Act; and – at least for now – continuing Deferred Action for Childhood Arrivals (DACA) protections that could allow recipients to stay in the country, study, and become doctors, and potentially provide care for up to 100,000 Americans, according to an estimate by the American Medical Association.

Dr. Worthing also noted that the ACR has an Insurance Subcommittee that has been instrumental in many of these and other policy wins, and he encouraged rheumatologists to contact the committee at Advocacy@rheumatology.org to report any sort of “canary-in-the-coal-mine” issues, such as refusal of coverage for a new step therapy, service, or item in your clinic that seems “absurd; doesn’t have merit.”

Send a copy of the policy behind the denial (with private health information redacted), or complete a Health Plan Complaint Form, which can be accessed at the website, he advised.

Rheumatologists can make their voices heard in other ways, he said. The ACR has a number of ongoing advocacy efforts addressing things like drug-pricing models, biosimilar agent interchangeability pathways, step therapy reform, workforce issues, and the need for higher dual X-ray absorptiometry (DXA) reimbursement.

The ACR’s Legislative Action Center offers prewritten letters on a number of timely topics, as well as information about legislators and legislation. An app is available that provides alerts about important legislation.

A timely example is DXA-related, bipartisan, bicameral legislation currently on the table that would more than double reimbursement and “improve access to this critical screening tool,” he said.

“Right now is an excellent time to tell your legislators – and there’s a prewritten letter at the [site] – that this is an important topic,” he said. “Right now, as we get into bills that might come out, spending bills or health-related bills coming up to 2020, it would be wonderful to get a lot of support behind this so that it might be added into some kind of package.”

A similar prewritten letter regarding an active bill that addresses paying off student loans for pediatricians going into subspecialties like pediatric rheumatology also is on the table and could help address workforce shortages, he noted.

“The First Amendment protects your right to petition the government for redress of grievances. I don’t have to tell you this is an era of huge tumult ... protecting [democracy and institutions], protecting your organizations, raising your voice is really important right now,” he said, referencing his new Twitter hashtag that encourages doing one #ThingADay. “You could think of advocacy as an extension of the Hippocratic oath to do no harm on a government and social level.”

Quoting Margaret Mead, Dr. Worthing reminded rheumatologists that their voices matter despite (and in fact, because of) their small numbers: “Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.”

Dr. Worthing reported having no disclosures.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Rheumatologists comprise a “tiny sliver” of the U.S. physician pie chart, but their voices are nevertheless being heard and making a difference regarding policies that affect the specialty, according to Angus B. Worthing, MD.

However, given the myriad policy issues on the table, more and louder voices are needed, he said at the annual meeting of the Florida Society of Rheumatology, where, as chair of the American College of Rheumatology’s Government Affairs Committee, he provided an “advocacy update” on the committee’s activities.

Recent ACR “wins” as outlined by Dr. Worthing include:

• The postponement and modification of proposed cuts to Evaluation & Management (E/M) current procedural terminology (CPT) codes.

“Last summer, Medicare proposed that instead of having low-complexity to high-complexity E/M codes, they would condense all of the doctor visits into one code, which would obviously enhance the reimbursement for low complexity, but ding and penalize the reimbursement for high-complexity visits like ours,” said Dr. Worthing, who also is a partner in a private rheumatology practice in the Washington area.

An ACR press release on the proposal led to pivotal coverage of the issue in the New York Times. “It looks like not only did they postpone those cuts, they modified [the proposal], and we’ll find out any day now in the proposal for the next year’s physician fee schedule whether they’ll scrap it entirely and instead try to plus-up E/M code reimbursement for complex patients.”

• The elimination of proposed Merit-based Incentive Payment System (MIPS) adjustments on Medicare drug reimbursement.

A cut to fee-for-service reimbursement for drug costs as a MIPS penalty could have quickly bankrupted rheumatology practices, Dr. Worthing said.

“[The success] was largely out of rheumatologists and others saying that this could quickly stop access to these treatments, because we wouldn’t be able to provide them,” he noted.

• The dampening of proposed musculoskeletal ultrasound reimbursement cuts in Medicare.

Ultrasound is a safe, effective, dynamic, and relatively low-cost diagnostic tool, but Medicare has been considering “absurd” cuts to reimbursement, Dr. Worthing said.

“We’ve been able to have good conversations with Medicare ... to bring that argument to Medicare, and we’ll find out – again, when the physician fee schedule comes out – whether they’ll continue the plan to cut diagnostic ultrasound reimbursement or whether they’ll stop cutting it.”

• The inclusion of more favorable Medicare Advantage regulations for step therapy “grandfathering.”

Medicare Advantage plans were given the chance last summer to use step therapy in Part B medicines for the first time.

“The ACR quickly told the executive branch and officials at [the Department of Health & Human Services (HHS)], that this would not be good for our patients getting medications,” Dr. Worthing said.

Going forward with that plan, and looking back just 108 days to allow people to stay on their medications – as was proposed – wouldn’t work, as some drugs are dosed every 4-6 months, or every year or every 2 years, he said.

“The look of astonishment on the [HHS] deputy secretary’s face when I told him that there was a drug in the U.S. that you give every 2 years was helpful for me to know that these people really need to hear from us before they issue these kinds of regulations,” he said.

The administration listened to the rheumatologists and is going to look back 365 days to keep people on their drugs, he said.

The ACR took the lead on these recent successes, but was also involved in a number of other wins achieved through multisociety efforts, he said.

Examples include securing a $2 billion increase in National Institutes of Health funding, eliminating “gag clauses” that prevent pharmacists from informing patients when it’s cheaper to just buy a drug rather than using their insurance; getting rid of annual caps on physical and other rehabilitation therapy for patients meeting their targets; repealing (before it could take effect) of the Independent Payment Advisory Board established by the Affordable Care Act; and – at least for now – continuing Deferred Action for Childhood Arrivals (DACA) protections that could allow recipients to stay in the country, study, and become doctors, and potentially provide care for up to 100,000 Americans, according to an estimate by the American Medical Association.

Dr. Worthing also noted that the ACR has an Insurance Subcommittee that has been instrumental in many of these and other policy wins, and he encouraged rheumatologists to contact the committee at Advocacy@rheumatology.org to report any sort of “canary-in-the-coal-mine” issues, such as refusal of coverage for a new step therapy, service, or item in your clinic that seems “absurd; doesn’t have merit.”

Send a copy of the policy behind the denial (with private health information redacted), or complete a Health Plan Complaint Form, which can be accessed at the website, he advised.

Rheumatologists can make their voices heard in other ways, he said. The ACR has a number of ongoing advocacy efforts addressing things like drug-pricing models, biosimilar agent interchangeability pathways, step therapy reform, workforce issues, and the need for higher dual X-ray absorptiometry (DXA) reimbursement.

The ACR’s Legislative Action Center offers prewritten letters on a number of timely topics, as well as information about legislators and legislation. An app is available that provides alerts about important legislation.

A timely example is DXA-related, bipartisan, bicameral legislation currently on the table that would more than double reimbursement and “improve access to this critical screening tool,” he said.

“Right now is an excellent time to tell your legislators – and there’s a prewritten letter at the [site] – that this is an important topic,” he said. “Right now, as we get into bills that might come out, spending bills or health-related bills coming up to 2020, it would be wonderful to get a lot of support behind this so that it might be added into some kind of package.”

A similar prewritten letter regarding an active bill that addresses paying off student loans for pediatricians going into subspecialties like pediatric rheumatology also is on the table and could help address workforce shortages, he noted.

“The First Amendment protects your right to petition the government for redress of grievances. I don’t have to tell you this is an era of huge tumult ... protecting [democracy and institutions], protecting your organizations, raising your voice is really important right now,” he said, referencing his new Twitter hashtag that encourages doing one #ThingADay. “You could think of advocacy as an extension of the Hippocratic oath to do no harm on a government and social level.”

Quoting Margaret Mead, Dr. Worthing reminded rheumatologists that their voices matter despite (and in fact, because of) their small numbers: “Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.”

Dr. Worthing reported having no disclosures.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Rheumatologists comprise a “tiny sliver” of the U.S. physician pie chart, but their voices are nevertheless being heard and making a difference regarding policies that affect the specialty, according to Angus B. Worthing, MD.

However, given the myriad policy issues on the table, more and louder voices are needed, he said at the annual meeting of the Florida Society of Rheumatology, where, as chair of the American College of Rheumatology’s Government Affairs Committee, he provided an “advocacy update” on the committee’s activities.

Recent ACR “wins” as outlined by Dr. Worthing include:

• The postponement and modification of proposed cuts to Evaluation & Management (E/M) current procedural terminology (CPT) codes.

“Last summer, Medicare proposed that instead of having low-complexity to high-complexity E/M codes, they would condense all of the doctor visits into one code, which would obviously enhance the reimbursement for low complexity, but ding and penalize the reimbursement for high-complexity visits like ours,” said Dr. Worthing, who also is a partner in a private rheumatology practice in the Washington area.

An ACR press release on the proposal led to pivotal coverage of the issue in the New York Times. “It looks like not only did they postpone those cuts, they modified [the proposal], and we’ll find out any day now in the proposal for the next year’s physician fee schedule whether they’ll scrap it entirely and instead try to plus-up E/M code reimbursement for complex patients.”

• The elimination of proposed Merit-based Incentive Payment System (MIPS) adjustments on Medicare drug reimbursement.

A cut to fee-for-service reimbursement for drug costs as a MIPS penalty could have quickly bankrupted rheumatology practices, Dr. Worthing said.

“[The success] was largely out of rheumatologists and others saying that this could quickly stop access to these treatments, because we wouldn’t be able to provide them,” he noted.

• The dampening of proposed musculoskeletal ultrasound reimbursement cuts in Medicare.

Ultrasound is a safe, effective, dynamic, and relatively low-cost diagnostic tool, but Medicare has been considering “absurd” cuts to reimbursement, Dr. Worthing said.

“We’ve been able to have good conversations with Medicare ... to bring that argument to Medicare, and we’ll find out – again, when the physician fee schedule comes out – whether they’ll continue the plan to cut diagnostic ultrasound reimbursement or whether they’ll stop cutting it.”

• The inclusion of more favorable Medicare Advantage regulations for step therapy “grandfathering.”

Medicare Advantage plans were given the chance last summer to use step therapy in Part B medicines for the first time.

“The ACR quickly told the executive branch and officials at [the Department of Health & Human Services (HHS)], that this would not be good for our patients getting medications,” Dr. Worthing said.

Going forward with that plan, and looking back just 108 days to allow people to stay on their medications – as was proposed – wouldn’t work, as some drugs are dosed every 4-6 months, or every year or every 2 years, he said.

“The look of astonishment on the [HHS] deputy secretary’s face when I told him that there was a drug in the U.S. that you give every 2 years was helpful for me to know that these people really need to hear from us before they issue these kinds of regulations,” he said.

The administration listened to the rheumatologists and is going to look back 365 days to keep people on their drugs, he said.

The ACR took the lead on these recent successes, but was also involved in a number of other wins achieved through multisociety efforts, he said.

Examples include securing a $2 billion increase in National Institutes of Health funding, eliminating “gag clauses” that prevent pharmacists from informing patients when it’s cheaper to just buy a drug rather than using their insurance; getting rid of annual caps on physical and other rehabilitation therapy for patients meeting their targets; repealing (before it could take effect) of the Independent Payment Advisory Board established by the Affordable Care Act; and – at least for now – continuing Deferred Action for Childhood Arrivals (DACA) protections that could allow recipients to stay in the country, study, and become doctors, and potentially provide care for up to 100,000 Americans, according to an estimate by the American Medical Association.

Dr. Worthing also noted that the ACR has an Insurance Subcommittee that has been instrumental in many of these and other policy wins, and he encouraged rheumatologists to contact the committee at Advocacy@rheumatology.org to report any sort of “canary-in-the-coal-mine” issues, such as refusal of coverage for a new step therapy, service, or item in your clinic that seems “absurd; doesn’t have merit.”

Send a copy of the policy behind the denial (with private health information redacted), or complete a Health Plan Complaint Form, which can be accessed at the website, he advised.

Rheumatologists can make their voices heard in other ways, he said. The ACR has a number of ongoing advocacy efforts addressing things like drug-pricing models, biosimilar agent interchangeability pathways, step therapy reform, workforce issues, and the need for higher dual X-ray absorptiometry (DXA) reimbursement.

The ACR’s Legislative Action Center offers prewritten letters on a number of timely topics, as well as information about legislators and legislation. An app is available that provides alerts about important legislation.

A timely example is DXA-related, bipartisan, bicameral legislation currently on the table that would more than double reimbursement and “improve access to this critical screening tool,” he said.

“Right now is an excellent time to tell your legislators – and there’s a prewritten letter at the [site] – that this is an important topic,” he said. “Right now, as we get into bills that might come out, spending bills or health-related bills coming up to 2020, it would be wonderful to get a lot of support behind this so that it might be added into some kind of package.”

A similar prewritten letter regarding an active bill that addresses paying off student loans for pediatricians going into subspecialties like pediatric rheumatology also is on the table and could help address workforce shortages, he noted.

“The First Amendment protects your right to petition the government for redress of grievances. I don’t have to tell you this is an era of huge tumult ... protecting [democracy and institutions], protecting your organizations, raising your voice is really important right now,” he said, referencing his new Twitter hashtag that encourages doing one #ThingADay. “You could think of advocacy as an extension of the Hippocratic oath to do no harm on a government and social level.”

Quoting Margaret Mead, Dr. Worthing reminded rheumatologists that their voices matter despite (and in fact, because of) their small numbers: “Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.”

Dr. Worthing reported having no disclosures.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.

Mitchel L. Zoler/MDedge News

During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.

Antihypertensive therapy

Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.

She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.

“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.

The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.

“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.

The problem is that many physicians think 110 or 112 is too low.

“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”

ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.

Hydroxychloroquine

Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.

“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”

Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.

Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.

In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).

“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
 

Vitamin D

Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.

In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).

“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
 

Mycophenolate mofetil

The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.

Left untreated, he would be in end-stage renal disease within a year, she said.

“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.

This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.

“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”

In this case, however, the best induction therapy is mycophenolate mofetil, she said.

“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”

In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.

After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”

“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.

“So we really need something that’s much more successful.”
 

Steroids

How much prednisone should lupus nephritis patients get?

As little as possible, according to Dr. Petri.

“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”

She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.

“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.

“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.

EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”

“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”

Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).

“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”

Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.

“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.

“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).

Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).

Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.

Mitchel L. Zoler/MDedge News

During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.

Antihypertensive therapy

Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.

She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.

“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.

The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.

“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.

The problem is that many physicians think 110 or 112 is too low.

“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”

ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.

Hydroxychloroquine

Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.

“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”

Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.

Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.

In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).

“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
 

Vitamin D

Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.

In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).

“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
 

Mycophenolate mofetil

The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.

Left untreated, he would be in end-stage renal disease within a year, she said.

“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.

This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.

“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”

In this case, however, the best induction therapy is mycophenolate mofetil, she said.

“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”

In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.

After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”

“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.

“So we really need something that’s much more successful.”
 

Steroids

How much prednisone should lupus nephritis patients get?

As little as possible, according to Dr. Petri.

“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”

She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.

“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.

“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.

EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”

“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”

Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).

“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”

Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.

“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.

“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).

Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).

Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.

Mitchel L. Zoler/MDedge News

During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.

Antihypertensive therapy

Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.

She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.

“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.

The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.

“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.

The problem is that many physicians think 110 or 112 is too low.

“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”

ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.

Hydroxychloroquine

Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.

“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”

Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.

Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.

In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).

“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
 

Vitamin D

Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.

In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).

“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
 

Mycophenolate mofetil

The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.

Left untreated, he would be in end-stage renal disease within a year, she said.

“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.

This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.

“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”

In this case, however, the best induction therapy is mycophenolate mofetil, she said.

“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”

In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.

After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”

“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.

“So we really need something that’s much more successful.”
 

Steroids

How much prednisone should lupus nephritis patients get?

As little as possible, according to Dr. Petri.

“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”

She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.

“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.

“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.

EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”

“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”

Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).

“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”

Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.

“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.

“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).

Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).

Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – “Crude and uninformed.”

That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.

Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.

“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.

According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.

“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.

“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.

A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.

The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.

“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”

However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.

“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.

A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).

“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”

Data needed to define best treatments

Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.

For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.

A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.

However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”

“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”

Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”

Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
 

Need for multidisciplinary collaboration

Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.

A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.

The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.

The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”

“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.

In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.

“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”

He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.

“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”

Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – “Crude and uninformed.”

That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.

Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.

“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.

According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.

“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.

“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.

A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.

The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.

“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”

However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.

“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.

A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).

“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”

Data needed to define best treatments

Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.

For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.

A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.

However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”

“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”

Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”

Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
 

Need for multidisciplinary collaboration

Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.

A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.

The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.

The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”

“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.

In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.

“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”

He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.

“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”

Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – “Crude and uninformed.”

That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.

Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.

“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.

According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.

“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.

“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.

A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.

The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.

“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”

However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.

“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.

A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).

“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”

Data needed to define best treatments

Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.

For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.

A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.

However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”

“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”

Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”

Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
 

Need for multidisciplinary collaboration

Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.

A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.

The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.

The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”

“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.

In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.

“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”

He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.

“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”

Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Wellness is an antidote to burnout.

That was the message from psychotherapist and author Saundra Jain, PsyD, during a talk focused on “reigniting the flame” in both professional and personal life.

©stanciuc/thinkstockphotos.com

“Wellness is not an afterthought. It simply cannot be,” she said at the annual meeting of the Florida Society of Rheumatology. The “data demand that wellness be elevated.”

That’s true both for patient care and for self care, she stressed, noting that by “wellness” she is referring to the 1948 World Health Organization definition: “... a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.”

Wellness-enhancing practices – she discussed five that have “the most robust dataset”: exercise, nutrition, mindfulness, social connectedness, and sleep – can improve well-being and reduce burnout through a number of mechanisms, not the least of which are reduced inflammation and reduced depression and anxiety, said Dr. Jain, adjunct clinical affiliate for the School of Nursing at the University of Texas at Austin.

For example, regular exercise is known to reduce chronic inflammation, and the effect has been shown to be independent of weight loss, she noted (Sports Med. 2013;43[4]:243-56).

Mindfulness also has been shown to reduce cortisol production in response to a psychological stressor, and thus may positively affect inflammatory responses, she said (Brain Behav Immun. 2013;27:174-184).

People struggle with the concept of mindfulness, because for many it is a bit foreign to their experience, she said, adding that “what we don’t know, we’re sometimes a little bit afraid of.

“But the data around mindfulness, honestly, is robust – it really, really is,” she said, adding that “you can take people who have not meditated at all, and in 8 weeks impact their inflammation.

“So you don’t have to be a long-term meditator – you do not have to meditate for 18 hours a day sitting in a lotus position in a serene, beautiful location.”

There is no right or wrong way to meditate; it’s all about the practice, she added.

In an effort to help her own patients find wellness, Dr. Jain cofounded the WILD 5 Wellness program and coauthored a related workbook and program called KickStart30 designed to help kick-start the wellness journey.

WILD stands for Wellness Interventions for Life’s Demands, and the program combines the five key evidence-based wellness elements into an easy-to-follow program, she said.

The KickStart30 workbook is available for purchase, with all profits benefiting mental health charities. The approach is as applicable for physician wellness as for patient wellness, she said. The program is simple, prescriptive, trackable, and self-contained, she added.

Wellness-enhancing practices as recommended in the program include:

• 30 minutes of exercise daily for 30 days, with an aim of at least moderate intensity.
• 10 minutes of mindfulness practice each day for 30 days. (Free guided meditations, which she and her colleagues use in their studies of the program, are available at www.WILD5Meditations.com, but a number of other guided meditation apps are available online, she said.) “Of the apps that are available, Headspace, without a doubt, is my favorite,” she said. It requires a paid subscription, but “is so worth it.”
• Implementation of at least four of six sleep hygiene practices each day for 30 days.
• Meeting or calling a minimum of two friends or family members each day for 30 days.
• Logging meals/snacks/beverages/alcohol consumption each day for 30 days, following the Mediterranean-DASH intervention for Neurodegenerative Delay (MIND) diet principles as closely as possible.

Program success requires effort, not perfection, in following the recommendations, and measurement and tracking are essential, Dr. Jain said, noting that a simple tracking tool – the KickStart30–HERO Wellness Scale – was validated in a recent study that has been accepted for publication in Annals of Psychology in the coming months).

A prior study of 82 participants, which she presented in 2016 in a poster at the 29th Annual U.S. Psychiatric and Mental Health Congress, showed that completion of the KickStart30 program was associated with improvements on a variety of wellness measures, including happiness (30%), enthusiasm (51%), resilience 63%, and optimism (45%), she said.

Participants also experienced important improvements in disease markers, including depression (43% based on the 9-item Patient Health Questionnaire), anxiety (40% as measured by the 7-item Generalized Anxiety Disorder scale), and sleep quality (29% based on the 9-item Pittsburgh Sleep Quality Index).

“The one thing I want when you leave and you think about this session is a feeling ... that ‘there are actually things that I can do to improve my wellness.’ There’s something about the power, the synergy between the elements ... it’s reigniting the flame, the interest in wellness,” she said, adding that taking care of others requires “learning to take better care of ourselves.”

“We have to walk the walk of wellness; we cannot simply sit in the ivory tower and talk about it,” she said. “To be genuine and to really engage our patients, we have to walk the walk.”

Dr. Jain is cofounder of the WILD 5 Wellness program, and has served on advisory boards or panels for numerous pharmaceutical companies and other organizations.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Wellness is an antidote to burnout.

That was the message from psychotherapist and author Saundra Jain, PsyD, during a talk focused on “reigniting the flame” in both professional and personal life.

©stanciuc/thinkstockphotos.com

“Wellness is not an afterthought. It simply cannot be,” she said at the annual meeting of the Florida Society of Rheumatology. The “data demand that wellness be elevated.”

That’s true both for patient care and for self care, she stressed, noting that by “wellness” she is referring to the 1948 World Health Organization definition: “... a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.”

Wellness-enhancing practices – she discussed five that have “the most robust dataset”: exercise, nutrition, mindfulness, social connectedness, and sleep – can improve well-being and reduce burnout through a number of mechanisms, not the least of which are reduced inflammation and reduced depression and anxiety, said Dr. Jain, adjunct clinical affiliate for the School of Nursing at the University of Texas at Austin.

For example, regular exercise is known to reduce chronic inflammation, and the effect has been shown to be independent of weight loss, she noted (Sports Med. 2013;43[4]:243-56).

Mindfulness also has been shown to reduce cortisol production in response to a psychological stressor, and thus may positively affect inflammatory responses, she said (Brain Behav Immun. 2013;27:174-184).

People struggle with the concept of mindfulness, because for many it is a bit foreign to their experience, she said, adding that “what we don’t know, we’re sometimes a little bit afraid of.

“But the data around mindfulness, honestly, is robust – it really, really is,” she said, adding that “you can take people who have not meditated at all, and in 8 weeks impact their inflammation.

“So you don’t have to be a long-term meditator – you do not have to meditate for 18 hours a day sitting in a lotus position in a serene, beautiful location.”

There is no right or wrong way to meditate; it’s all about the practice, she added.

In an effort to help her own patients find wellness, Dr. Jain cofounded the WILD 5 Wellness program and coauthored a related workbook and program called KickStart30 designed to help kick-start the wellness journey.

WILD stands for Wellness Interventions for Life’s Demands, and the program combines the five key evidence-based wellness elements into an easy-to-follow program, she said.

The KickStart30 workbook is available for purchase, with all profits benefiting mental health charities. The approach is as applicable for physician wellness as for patient wellness, she said. The program is simple, prescriptive, trackable, and self-contained, she added.

Wellness-enhancing practices as recommended in the program include:

• 30 minutes of exercise daily for 30 days, with an aim of at least moderate intensity.
• 10 minutes of mindfulness practice each day for 30 days. (Free guided meditations, which she and her colleagues use in their studies of the program, are available at www.WILD5Meditations.com, but a number of other guided meditation apps are available online, she said.) “Of the apps that are available, Headspace, without a doubt, is my favorite,” she said. It requires a paid subscription, but “is so worth it.”
• Implementation of at least four of six sleep hygiene practices each day for 30 days.
• Meeting or calling a minimum of two friends or family members each day for 30 days.
• Logging meals/snacks/beverages/alcohol consumption each day for 30 days, following the Mediterranean-DASH intervention for Neurodegenerative Delay (MIND) diet principles as closely as possible.

Program success requires effort, not perfection, in following the recommendations, and measurement and tracking are essential, Dr. Jain said, noting that a simple tracking tool – the KickStart30–HERO Wellness Scale – was validated in a recent study that has been accepted for publication in Annals of Psychology in the coming months).

A prior study of 82 participants, which she presented in 2016 in a poster at the 29th Annual U.S. Psychiatric and Mental Health Congress, showed that completion of the KickStart30 program was associated with improvements on a variety of wellness measures, including happiness (30%), enthusiasm (51%), resilience 63%, and optimism (45%), she said.

Participants also experienced important improvements in disease markers, including depression (43% based on the 9-item Patient Health Questionnaire), anxiety (40% as measured by the 7-item Generalized Anxiety Disorder scale), and sleep quality (29% based on the 9-item Pittsburgh Sleep Quality Index).

“The one thing I want when you leave and you think about this session is a feeling ... that ‘there are actually things that I can do to improve my wellness.’ There’s something about the power, the synergy between the elements ... it’s reigniting the flame, the interest in wellness,” she said, adding that taking care of others requires “learning to take better care of ourselves.”

“We have to walk the walk of wellness; we cannot simply sit in the ivory tower and talk about it,” she said. “To be genuine and to really engage our patients, we have to walk the walk.”

Dr. Jain is cofounder of the WILD 5 Wellness program, and has served on advisory boards or panels for numerous pharmaceutical companies and other organizations.

sworcester@mdedge.com

LAKE BUENA VISTA, FLA. – Wellness is an antidote to burnout.

That was the message from psychotherapist and author Saundra Jain, PsyD, during a talk focused on “reigniting the flame” in both professional and personal life.

©stanciuc/thinkstockphotos.com

“Wellness is not an afterthought. It simply cannot be,” she said at the annual meeting of the Florida Society of Rheumatology. The “data demand that wellness be elevated.”

That’s true both for patient care and for self care, she stressed, noting that by “wellness” she is referring to the 1948 World Health Organization definition: “... a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.”

Wellness-enhancing practices – she discussed five that have “the most robust dataset”: exercise, nutrition, mindfulness, social connectedness, and sleep – can improve well-being and reduce burnout through a number of mechanisms, not the least of which are reduced inflammation and reduced depression and anxiety, said Dr. Jain, adjunct clinical affiliate for the School of Nursing at the University of Texas at Austin.

For example, regular exercise is known to reduce chronic inflammation, and the effect has been shown to be independent of weight loss, she noted (Sports Med. 2013;43[4]:243-56).

Mindfulness also has been shown to reduce cortisol production in response to a psychological stressor, and thus may positively affect inflammatory responses, she said (Brain Behav Immun. 2013;27:174-184).

People struggle with the concept of mindfulness, because for many it is a bit foreign to their experience, she said, adding that “what we don’t know, we’re sometimes a little bit afraid of.

“But the data around mindfulness, honestly, is robust – it really, really is,” she said, adding that “you can take people who have not meditated at all, and in 8 weeks impact their inflammation.

“So you don’t have to be a long-term meditator – you do not have to meditate for 18 hours a day sitting in a lotus position in a serene, beautiful location.”

There is no right or wrong way to meditate; it’s all about the practice, she added.

In an effort to help her own patients find wellness, Dr. Jain cofounded the WILD 5 Wellness program and coauthored a related workbook and program called KickStart30 designed to help kick-start the wellness journey.

WILD stands for Wellness Interventions for Life’s Demands, and the program combines the five key evidence-based wellness elements into an easy-to-follow program, she said.

The KickStart30 workbook is available for purchase, with all profits benefiting mental health charities. The approach is as applicable for physician wellness as for patient wellness, she said. The program is simple, prescriptive, trackable, and self-contained, she added.

Wellness-enhancing practices as recommended in the program include:

• 30 minutes of exercise daily for 30 days, with an aim of at least moderate intensity.
• 10 minutes of mindfulness practice each day for 30 days. (Free guided meditations, which she and her colleagues use in their studies of the program, are available at www.WILD5Meditations.com, but a number of other guided meditation apps are available online, she said.) “Of the apps that are available, Headspace, without a doubt, is my favorite,” she said. It requires a paid subscription, but “is so worth it.”
• Implementation of at least four of six sleep hygiene practices each day for 30 days.
• Meeting or calling a minimum of two friends or family members each day for 30 days.
• Logging meals/snacks/beverages/alcohol consumption each day for 30 days, following the Mediterranean-DASH intervention for Neurodegenerative Delay (MIND) diet principles as closely as possible.

Program success requires effort, not perfection, in following the recommendations, and measurement and tracking are essential, Dr. Jain said, noting that a simple tracking tool – the KickStart30–HERO Wellness Scale – was validated in a recent study that has been accepted for publication in Annals of Psychology in the coming months).

A prior study of 82 participants, which she presented in 2016 in a poster at the 29th Annual U.S. Psychiatric and Mental Health Congress, showed that completion of the KickStart30 program was associated with improvements on a variety of wellness measures, including happiness (30%), enthusiasm (51%), resilience 63%, and optimism (45%), she said.

Participants also experienced important improvements in disease markers, including depression (43% based on the 9-item Patient Health Questionnaire), anxiety (40% as measured by the 7-item Generalized Anxiety Disorder scale), and sleep quality (29% based on the 9-item Pittsburgh Sleep Quality Index).

“The one thing I want when you leave and you think about this session is a feeling ... that ‘there are actually things that I can do to improve my wellness.’ There’s something about the power, the synergy between the elements ... it’s reigniting the flame, the interest in wellness,” she said, adding that taking care of others requires “learning to take better care of ourselves.”

“We have to walk the walk of wellness; we cannot simply sit in the ivory tower and talk about it,” she said. “To be genuine and to really engage our patients, we have to walk the walk.”

Dr. Jain is cofounder of the WILD 5 Wellness program, and has served on advisory boards or panels for numerous pharmaceutical companies and other organizations.

sworcester@mdedge.com

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

mzoler@mdedge.com

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

mzoler@mdedge.com

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

mzoler@mdedge.com

Clinical question: In patients with hypertension, chronic kidney disease, or heart failure presenting with a musculoskeletal disorder, how frequently are prescription NSAIDs dispensed and are there associated short-term (between 7-38 days of visit) safety-related outcomes?

Background: Multiple expert panels recommend against the use of NSAIDs in patients with hypertension (HTN), chronic kidney disease (CKD), or heart failure (HF). Previous studies have demonstrated an increased risk of cardiovascular events and renal injury with long-term NSAID use.

Study design: Retrospective cohort study.

Setting: Population-based administrative claims database identified primary care visits in Ontario.

Dr. Stanley is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: In patients with hypertension, chronic kidney disease, or heart failure presenting with a musculoskeletal disorder, how frequently are prescription NSAIDs dispensed and are there associated short-term (between 7-38 days of visit) safety-related outcomes?

Background: Multiple expert panels recommend against the use of NSAIDs in patients with hypertension (HTN), chronic kidney disease (CKD), or heart failure (HF). Previous studies have demonstrated an increased risk of cardiovascular events and renal injury with long-term NSAID use.

Study design: Retrospective cohort study.

Setting: Population-based administrative claims database identified primary care visits in Ontario.

Dr. Stanley is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: In patients with hypertension, chronic kidney disease, or heart failure presenting with a musculoskeletal disorder, how frequently are prescription NSAIDs dispensed and are there associated short-term (between 7-38 days of visit) safety-related outcomes?

Background: Multiple expert panels recommend against the use of NSAIDs in patients with hypertension (HTN), chronic kidney disease (CKD), or heart failure (HF). Previous studies have demonstrated an increased risk of cardiovascular events and renal injury with long-term NSAID use.

Study design: Retrospective cohort study.

Setting: Population-based administrative claims database identified primary care visits in Ontario.

Dr. Stanley is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Pediatric non-Hodgkin lymphomas should be added to the list of cancers associated with BRCA2 mutations, and survivors of childhood NHL should be considered for genetic counseling, investigators suggest.

Among 1,380 survivors of childhood lymphomas, those who were retrospectively found to be carriers of BRCA2 mutations had a fivefold higher risk for non-Hodgkin lymphoma than controls without cancer, reported Zhaoming Wang, PhD, and colleagues from St. Jude Children’s Research Hospital in Memphis.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non–Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” they wrote in JAMA Oncology.

The investigators had previously reported that BRCA2 was the third-most frequently mutated gene among 3006 survivors of childhood cancers, with the highest number of mutations seen in lymphoma survivors. In that study, 7 of 586 survivors of Hodgkin and non-Hodgkin lymphoma (1.2%) were found to carry BRCA2 mutations.

In the current study, the investigators performed germline whole-genome sequencing on samples from 815 survivors of childhood Hodgkin lymphoma and 748 survivors of non-Hodgkin lymphoma from the St. Jude Lifetime Cohort and Childhood Cancer Survivor studies and compared the data with those of controls without cancer from the Genome Aggregation Database.

They identified mutations in five Hodgkin lymphoma survivors (0.6%) and eight non-Hodgkin lymphoma survivors.

A comparison of cancer risk among lymphoma survivors and controls found that non-Hodgkin lymphoma survivors and BRCA2 carriers had an odds ratio for cancer of 5.0, compared with controls who were not BRCA2 carriers (P less than .001). Among Hodgkin lymphoma survivors the OR for carriers vs. controls was 2.1, but was not statistically significant.

Available family histories for seven of the eight non-Hodgkin lymphoma BRCA2 mutation carriers showed histories of BRCA2-linked cancers, including breast, prostate, and pancreas tumors and malignant melanoma.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies. Currently, it remains unclear whether surveillance for non–Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantages,” the investigators wrote.

“This study was funded by a grant to St Jude Children’s Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St Jude Children’s Research Hospital from the National Institutes of Health. The authors reported having no conflicts of interest.

SOURCE: Wang Z et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2203.

Pediatric non-Hodgkin lymphomas should be added to the list of cancers associated with BRCA2 mutations, and survivors of childhood NHL should be considered for genetic counseling, investigators suggest.

Among 1,380 survivors of childhood lymphomas, those who were retrospectively found to be carriers of BRCA2 mutations had a fivefold higher risk for non-Hodgkin lymphoma than controls without cancer, reported Zhaoming Wang, PhD, and colleagues from St. Jude Children’s Research Hospital in Memphis.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non–Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” they wrote in JAMA Oncology.

The investigators had previously reported that BRCA2 was the third-most frequently mutated gene among 3006 survivors of childhood cancers, with the highest number of mutations seen in lymphoma survivors. In that study, 7 of 586 survivors of Hodgkin and non-Hodgkin lymphoma (1.2%) were found to carry BRCA2 mutations.

In the current study, the investigators performed germline whole-genome sequencing on samples from 815 survivors of childhood Hodgkin lymphoma and 748 survivors of non-Hodgkin lymphoma from the St. Jude Lifetime Cohort and Childhood Cancer Survivor studies and compared the data with those of controls without cancer from the Genome Aggregation Database.

They identified mutations in five Hodgkin lymphoma survivors (0.6%) and eight non-Hodgkin lymphoma survivors.

A comparison of cancer risk among lymphoma survivors and controls found that non-Hodgkin lymphoma survivors and BRCA2 carriers had an odds ratio for cancer of 5.0, compared with controls who were not BRCA2 carriers (P less than .001). Among Hodgkin lymphoma survivors the OR for carriers vs. controls was 2.1, but was not statistically significant.

Available family histories for seven of the eight non-Hodgkin lymphoma BRCA2 mutation carriers showed histories of BRCA2-linked cancers, including breast, prostate, and pancreas tumors and malignant melanoma.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies. Currently, it remains unclear whether surveillance for non–Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantages,” the investigators wrote.

“This study was funded by a grant to St Jude Children’s Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St Jude Children’s Research Hospital from the National Institutes of Health. The authors reported having no conflicts of interest.

SOURCE: Wang Z et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2203.

Pediatric non-Hodgkin lymphomas should be added to the list of cancers associated with BRCA2 mutations, and survivors of childhood NHL should be considered for genetic counseling, investigators suggest.

Among 1,380 survivors of childhood lymphomas, those who were retrospectively found to be carriers of BRCA2 mutations had a fivefold higher risk for non-Hodgkin lymphoma than controls without cancer, reported Zhaoming Wang, PhD, and colleagues from St. Jude Children’s Research Hospital in Memphis.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non–Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” they wrote in JAMA Oncology.

The investigators had previously reported that BRCA2 was the third-most frequently mutated gene among 3006 survivors of childhood cancers, with the highest number of mutations seen in lymphoma survivors. In that study, 7 of 586 survivors of Hodgkin and non-Hodgkin lymphoma (1.2%) were found to carry BRCA2 mutations.

In the current study, the investigators performed germline whole-genome sequencing on samples from 815 survivors of childhood Hodgkin lymphoma and 748 survivors of non-Hodgkin lymphoma from the St. Jude Lifetime Cohort and Childhood Cancer Survivor studies and compared the data with those of controls without cancer from the Genome Aggregation Database.

They identified mutations in five Hodgkin lymphoma survivors (0.6%) and eight non-Hodgkin lymphoma survivors.

A comparison of cancer risk among lymphoma survivors and controls found that non-Hodgkin lymphoma survivors and BRCA2 carriers had an odds ratio for cancer of 5.0, compared with controls who were not BRCA2 carriers (P less than .001). Among Hodgkin lymphoma survivors the OR for carriers vs. controls was 2.1, but was not statistically significant.

Available family histories for seven of the eight non-Hodgkin lymphoma BRCA2 mutation carriers showed histories of BRCA2-linked cancers, including breast, prostate, and pancreas tumors and malignant melanoma.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies. Currently, it remains unclear whether surveillance for non–Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantages,” the investigators wrote.

“This study was funded by a grant to St Jude Children’s Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St Jude Children’s Research Hospital from the National Institutes of Health. The authors reported having no conflicts of interest.

SOURCE: Wang Z et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2203.