Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Only 1 child from a cohort of 45 children hospitalized with multisystem inflammatory syndrome following COVID-19 infection had persistent mild cardiac dysfunction after 9 months, according to data from patients younger than 21 years seen at a single center in 2020.

In a study published in Pediatrics, Kanwal M. Farooqi, MD, of Columbia University, New York, and colleagues provided the first report on longitudinal cardiac and immunologic outcomes in North American children hospitalized with multisystem inflammatory syndrome (MIS-C). In response to the COVID-19 pandemic, clinicians at New York–Presbyterian Hospital consolidated pediatric admissions and developed an interdisciplinary inpatient and outpatient MIS-C follow-up program to monitor cardiac and immunologic outcomes in their patients.

The study included all children younger than 21 years admitted to Columbia University Irving Medical Center/New York–Presbyterian Morgan Stanley Children’s Hospital for MIS-C in 2020. The median age of the patients was 9 years, and the median length of hospital stay was 5 days. Follow-up visits occurred at 1-4 weeks (average 2 weeks), 1-4 months (average 2 months), and 4-9 months (average 6 months) after hospital discharge. Follow-up visits included echocardiograms and measures of inflammatory markers.

Most of the children (84%) had no underlying medical conditions, but 24% presented with some level of respiratory distress or oxygen requirement, and 64% had vasodilatory shock. In addition, 80% had at least mild cardiac abnormalities and 66% had significant lymphopenia on admission.

Inflammatory profiles on admission showed elevation of C-reactive protein, ferritin, and D-dimer in 87%-98% of the patients. Consistent with cardiac involvement, 64% of the patients also had elevated troponin levels, and 91% had elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

“These parameters peaked at or shortly after admission and then gradually normalized,” the researchers said. “By the first follow-up, [C-reactive protein], troponin, and NT-proBNP had normalized in nearly all tested patients (97%-100%),” they noted.

By the first follow-up period at 1-4 weeks, all patients had normal coronary arteries, and 18% (seven patients) had mild echocardiographic findings. However, approximately one-third (32%) of the patients had persistent lymphocytosis at 1-4 weeks, and 23 of the 24 patients assessed had elevated double-negative T cells, which persisted in 96% of the patients at 1-4 months’ follow-up. However, during the last follow-up of 4-9 months, only one patient had persistent mild biventricular dysfunction and a second patient had mild mitral and tricuspid valve regurgitation.

All patients were treated with steroids and immunoglobulins (2 g/kg), as well as enoxaparin prophylaxis or low-dose aspirin and GI prophylaxis. Treatment with methylprednisolone varied based on disease severity; patients with mild presentation received 2 mg/kg per day; those with moderate presentation received a methylprednisolone pulse of 10 mg/kg per day, followed by 2 mg/kg per day; those with severe disease received methylprednisolone at 20-30 mg/kg per day for 1-3 days, followed by 2 mg/kg per day.

“Aggressive use of steroids may also explain the lower incidence of coronary artery abnormalities in our cohort,” the researchers noted.

The study findings were limited by the observational design and inability to make definitive conclusions about treatment and outcomes, as well as the evolving case definitions for MIS-C, the researchers said.

The persistence of double-negative T cells was surprising, and “likely represent a prolonged postinflammatory recovery cell population, but further study is ongoing to better define this observation,” they noted.

“Our study reveals generally encouraging medium-term outcomes, including rapid normalization of inflammatory markers and significant cardiac abnormalities in the majority of patients with MIS-C,” the researchers said. “The exact nature and potential for long-term cardiac fibrosis, exercise intolerance, or other changes remain unknown,” and long-term caution and follow-up are recommended, they concluded.
 

Cautious optimism, long-term monitoring

The study is important to provide guidance for clinicians on how to manage their patients who have been hospitalized with MIS-C, said Susan Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H.

“It was both surprising and reassuring to see that so many of the patients had positive outcomes in terms of cardiac function and that during the acute stage there were no deaths,” said Dr. Boulter. “Hospitalizations were brief, averaging just 5 days. The patients had many symptoms, but unlike adults, there was not a preponderance of underlying risk factors in this cohort of patients,” she said.

The results suggest optimism for MIS-C patients in that they generally recover, but the take-home message for clinicians is that these patients will require careful monitoring for long-term issues, Dr. Boulter said.

“These patients should be followed for years to assess long-term effects on morbidity and mortality,” Dr. Boulter emphasized.

The study was funded by Genentech. The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Background: In order to reduce the mismatch between patients’ desired and actual end-of-life care, the Physician Orders for Life-Sustaining Treatment (POLST) was created. POLST is a portable document delineating medical orders for emergency care treatment at the end of life including whether to attempt resuscitation and general level of medical interventions. For nursing home residents, an association between POLST creation and reduction of unwanted CPR has been substantiated. Outside of this population, the association is unknown.

Study design: Retrospective cohort study.

Setting: Two academic hospitals in Washington.

Synopsis: Patients older than age 18 years who had one of nine chronic health conditions associated with 90% of deaths among Medicare beneficiaries were identified using Washington state death certificates. Additional inclusion criteria included hospital admission in the last 6 months of life and creation of a POLST prior to this admission. This led to identification of 1,818 patients. Patients with full-treatment POLST orders were significantly more likely to be admitted to the ICU as well as receive life-sustaining treatments such as mechanical ventilation, vasoactive infusions, or CPR, compared with patients with limited interventions or comfort-only POLST orders (P < .001 for both). 38% of patients with treatment-limiting POLSTs received aggressive end-of-life care that was discordant with their previously documented wishes.

Bottom line: Completion of POLST was associated with a greater likelihood of receiving end-of-life care that was in line with patients’ previously documented wishes regarding admission to ICU and life-sustaining treatment. Washington was one of the first states to adopt POLST in 2005 and therefore these results may not be broadly applicable.

Citation: Lee RY et al. Association of physician orders for life-sustaining treatment with ICU admission among patients hospitalized hear the end of life. JAMA. 2020 Feb 16;323(10):950-60.

Dr. Dreicer is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: In order to reduce the mismatch between patients’ desired and actual end-of-life care, the Physician Orders for Life-Sustaining Treatment (POLST) was created. POLST is a portable document delineating medical orders for emergency care treatment at the end of life including whether to attempt resuscitation and general level of medical interventions. For nursing home residents, an association between POLST creation and reduction of unwanted CPR has been substantiated. Outside of this population, the association is unknown.

Study design: Retrospective cohort study.

Setting: Two academic hospitals in Washington.

Synopsis: Patients older than age 18 years who had one of nine chronic health conditions associated with 90% of deaths among Medicare beneficiaries were identified using Washington state death certificates. Additional inclusion criteria included hospital admission in the last 6 months of life and creation of a POLST prior to this admission. This led to identification of 1,818 patients. Patients with full-treatment POLST orders were significantly more likely to be admitted to the ICU as well as receive life-sustaining treatments such as mechanical ventilation, vasoactive infusions, or CPR, compared with patients with limited interventions or comfort-only POLST orders (P < .001 for both). 38% of patients with treatment-limiting POLSTs received aggressive end-of-life care that was discordant with their previously documented wishes.

Bottom line: Completion of POLST was associated with a greater likelihood of receiving end-of-life care that was in line with patients’ previously documented wishes regarding admission to ICU and life-sustaining treatment. Washington was one of the first states to adopt POLST in 2005 and therefore these results may not be broadly applicable.

Citation: Lee RY et al. Association of physician orders for life-sustaining treatment with ICU admission among patients hospitalized hear the end of life. JAMA. 2020 Feb 16;323(10):950-60.

Dr. Dreicer is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: In order to reduce the mismatch between patients’ desired and actual end-of-life care, the Physician Orders for Life-Sustaining Treatment (POLST) was created. POLST is a portable document delineating medical orders for emergency care treatment at the end of life including whether to attempt resuscitation and general level of medical interventions. For nursing home residents, an association between POLST creation and reduction of unwanted CPR has been substantiated. Outside of this population, the association is unknown.

Study design: Retrospective cohort study.

Setting: Two academic hospitals in Washington.

Synopsis: Patients older than age 18 years who had one of nine chronic health conditions associated with 90% of deaths among Medicare beneficiaries were identified using Washington state death certificates. Additional inclusion criteria included hospital admission in the last 6 months of life and creation of a POLST prior to this admission. This led to identification of 1,818 patients. Patients with full-treatment POLST orders were significantly more likely to be admitted to the ICU as well as receive life-sustaining treatments such as mechanical ventilation, vasoactive infusions, or CPR, compared with patients with limited interventions or comfort-only POLST orders (P < .001 for both). 38% of patients with treatment-limiting POLSTs received aggressive end-of-life care that was discordant with their previously documented wishes.

Bottom line: Completion of POLST was associated with a greater likelihood of receiving end-of-life care that was in line with patients’ previously documented wishes regarding admission to ICU and life-sustaining treatment. Washington was one of the first states to adopt POLST in 2005 and therefore these results may not be broadly applicable.

Citation: Lee RY et al. Association of physician orders for life-sustaining treatment with ICU admission among patients hospitalized hear the end of life. JAMA. 2020 Feb 16;323(10):950-60.

Dr. Dreicer is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Practicing rheumatologists in the United States received more than $220 million from pharmaceutical companies during 2014-2019, with payments increasing each year, according to findings from a descriptive study of the Centers for Medicare & Medicaid Services Open Payments Database.

Rheumatologists have identified conflicts of interest as an ethical concern, but the details of industry payments to rheumatologists have not been investigated, wrote Michael Putman, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues in Arthritis & Rheumatology. “Payments among rheumatologists may be of particular interest,” given their frequent prescription of expensive and primarily on-patent biologic and targeted disease-modifying antirheumatic drugs (DMARDs), the researchers said.

Over the 2014-2019 study period, 5,723 rheumatologists received a total of $221,254,966 from 1,610,668 payments. Of these, 3,416 (59%) received less than $5,000; 368 (6%) received more than $100,000, accounting for 78% of the total payments. The yearly value of the payments increased from $29,755,133 in 2014 to $46,308,926 in 2019, a 56% increase.

The payments to individual rheumatologists during the study period ranged from $8 to $5,612,254, with a median individual payment of $2,818. However, most (81%) of the payments were less than $25, and only 4% were more than $1,000.

Physicians who received more than $100,000 were significantly more likely to be paid speakers’ fees, consulting fees, and travel and lodging fees, but significantly less likely to receive payments for food and beverage than were those who received less than $100,000.

Overall, women made up 43% of the study population and received 34% of the total payments.

However, the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,732 vs. $2,084). Female rheumatologists were significantly more likely to receive payments for food and beverage and significantly less likely to receive speakers’ fees or travel and lodging coverage.

When the data were analyzed by state, California had the highest amount of total payments ($27,769,124), followed by New York and Texas, while Arizona had the highest spending per rheumatologist ($143,559). By region, based on U.S. Census divisions, the highest spending occurred in the Middle Atlantic Division ($46,327,351) and the highest per rheumatologist spending occurred in the East-South Central Division ($49,605).

“These data suggest industry payments in rheumatology have followed two distinct patterns, which have been observed in other medical subspecialties,” specifically, that many small payments are made to a large number of physicians, and large-value payments are made to a small number of physicians, the researchers noted.

The impact of small payments cannot be discounted, they said, “as even small gifts may affect behavior and are associated with prescribing patterns.” The impact of large payments on behavior and practice deserve further investigation, “but it is notable that a recent evaluation of rheumatology clinical practice guidelines identified substantial involvement from rheumatologists who had accepted large values of industry payments,” the researchers added.

Approximately half the total value of payments came from three companies: Bristol-Myers Squibb (20%), Abbvie (17%), and Pfizer (12%). Medications associated with the highest spending included Otezla, Humira, and Xeljanz.

Of note, the data showed that H.P. Acthar gel was among the top 10 agents for total payments, and “over 90% of rheumatologists who frequently prescribe H.P. Acthar gel have also received H.P. Acthar–related payments, raising the possibility that such payments have influenced prescribing behavior,” given the lack of high-quality evidence to support its use and the availability of less expensive alternatives, the researchers said.

The study findings were limited by several factors, including the focus only on general payments to rheumatologists, and the lack of external sources to verify payments, the researchers noted. “Most importantly, this was a descriptive study, and the degree to which payments have influenced physician behavior lies outside the scope of this work. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.”

Focus on collaborations that add value

The study is important because previous data on the magnitude of payments or payment patterns from pharmaceutical companies to practicing rheumatologists were limited, lead author Dr. Putman said in an interview.

“I was most surprised by some of the medications that received high values of payments,” he said. “Many payments were linked to medications that we use commonly and that have high-quality data supporting their use. That was not surprising, and you could imagine dollars spent on [interleukin]-23 or IL-17 inhibitors being used in a way that is valuable to other physicians or to patients with rheumatic diseases. On the other hand, some medications – most notably H.P. Acthar gel – have no high-quality data supporting their use, are used by a very small cadre of physicians, and are extraordinarily expensive. At least in my opinion, there is no world where payments linked to H.P. Acthar gel provide any benefit for physicians or patients.”

Dr. Putman said he expected that the patterns and the increases observed in the study are likely to continue.

“Ultimately, I have a somewhat nuanced view of financial conflicts of interest,” he said. “Collaborations between the pharmaceutical industry and rheumatologists have provided extraordinary value to our field. I think rheumatologists should be much more involved in some areas. At the same time, I think we should be much less involved in marketing drugs that provide little value to patients and great cost to society. H.P. Acthar Gel is the classic example of this, but there are others as well. I think future research should focus on how these payments influence behavior and should seek to identify areas where they result in low-value care.” Going forward, valuable collaborations between rheumatologists and the pharmaceutical industry should be encouraged, but collaborations without value should be discouraged, he said.
 

Industry payments serve no useful purpose

The findings “highlight the overarching concern regarding the ability of industry payments to adversely affect care quality within the specific context of rheumatology practice,” Aaron P. Mitchell, MD, of Memorial Sloan Kettering Cancer Center, New York, wrote in an accompanying editorial.

Dr. Mitchell emphasized several points, starting with the temporal trend showing an increase in industry payments beyond the rate of inflation that has not been universal across specialties. He also emphasized the “highly skewed distribution of payments,” with a large majority going to a relatively small number of rheumatologists. “This suggests an industry strategy of targeting ‘key opinion leaders,’ or KOLs, with higher payments,” and which was not surprising, as similar patterns have been seen in other specialties. Dr. Mitchell noted that 10 drugs accounted for more than half of the payments, and that “the unifying feature of these drugs is their high cost.”

“The picture of industry strategy that emerges from Putman et al. and other similar reports is that of intense, sustained KOL-focused marketing soon after the release of a new high-margin drug,” he wrote.

Despite the descriptive nature of the study, the findings have clinical implications based on other studies of the consequences of industry payments with respect to care quality, Dr. Mitchell said. “Hypothetically, industry spending to promote drugs to physicians could increase dissemination of new, superior drugs, improving patient outcomes.” However, physicians tend to opt for game-changing drugs without added incentive; “it is the less-innovative drugs that industry has to push harder.”

The practice of industry payments for physicians becomes even more difficult to rationalize given the potential for increased out-of-pocket costs and potentially avoidable toxicities for patients, Dr. Mitchell said. “Moreover, industry payments serve no unmet need; through our professional societies and other nonprofit sources, we physicians are fully capable of staying up-to-date on new treatments without relying on industry meals and sponsored events.”
 

Disclosure of payments is important

The study is important because it is essential to understand how public disclosure of industry payments influences financial relationship between the biomedical industry and physicians, said Amarnath Annapureddy, MD, a clinical fellow in cardiology at Yale University, New Haven, Conn., who has studied and written about industry payments to physicians.

Dr. Annapureddy said in an interview that he was surprised by how the study findings were opposite to the assumption that public disclosure would dissuade continuation of financial ties between physicians and industry. “This study showed payments increased over time rather than decreasing due to public disclosure.”

However, Dr. Annapureddy said that he was not surprised at how few physicians received the bulk of industry payments. “These physicians are considered to be ‘key opinion leaders’ who could influence practicing patterns of other physicians. These findings are similar to payment patterns for other specialties, including cardiology.

“So far, no study has evaluated factors that drive changes in industry payment patterns,” Dr. Annapureddy said. “I anticipate the patterns noted in this study will continue at least in the short term. If health care systems mandate physicians to disclose potential conflicts of interest to the patients, it may reduce payments.”

However, “unless, there is a major health policy mandate by government, I anticipate public disclosure of payments through the open payments program will not impact industry-physician ties,” he said. “This study has not evaluated impact of payments on prescribing practices. There are overwhelming data from several studies that showed payments influence physicians practicing patterns, whether it is prescribing a medication or implanting a device.” However, as for additional research, Dr. Annapureddy said that it would interesting to see a randomized trial to show whether the way physicians disclose their financial ties with patients would impact their practicing patterns.

The study received no outside funding. Dr. Putman was supported by a Rheumatology Research grant, but he and the other researchers had no financial conflicts to disclose. Dr. Mitchell disclosed a merit award from the nonprofit Conquer Cancer Foundation, for which the Foundation received financial support from Merck. Dr. Annapureddy had no financial conflicts to disclose.

Practicing rheumatologists in the United States received more than $220 million from pharmaceutical companies during 2014-2019, with payments increasing each year, according to findings from a descriptive study of the Centers for Medicare & Medicaid Services Open Payments Database.

Rheumatologists have identified conflicts of interest as an ethical concern, but the details of industry payments to rheumatologists have not been investigated, wrote Michael Putman, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues in Arthritis & Rheumatology. “Payments among rheumatologists may be of particular interest,” given their frequent prescription of expensive and primarily on-patent biologic and targeted disease-modifying antirheumatic drugs (DMARDs), the researchers said.

Over the 2014-2019 study period, 5,723 rheumatologists received a total of $221,254,966 from 1,610,668 payments. Of these, 3,416 (59%) received less than $5,000; 368 (6%) received more than $100,000, accounting for 78% of the total payments. The yearly value of the payments increased from $29,755,133 in 2014 to $46,308,926 in 2019, a 56% increase.

The payments to individual rheumatologists during the study period ranged from $8 to $5,612,254, with a median individual payment of $2,818. However, most (81%) of the payments were less than $25, and only 4% were more than $1,000.

Physicians who received more than $100,000 were significantly more likely to be paid speakers’ fees, consulting fees, and travel and lodging fees, but significantly less likely to receive payments for food and beverage than were those who received less than $100,000.

Overall, women made up 43% of the study population and received 34% of the total payments.

However, the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,732 vs. $2,084). Female rheumatologists were significantly more likely to receive payments for food and beverage and significantly less likely to receive speakers’ fees or travel and lodging coverage.

When the data were analyzed by state, California had the highest amount of total payments ($27,769,124), followed by New York and Texas, while Arizona had the highest spending per rheumatologist ($143,559). By region, based on U.S. Census divisions, the highest spending occurred in the Middle Atlantic Division ($46,327,351) and the highest per rheumatologist spending occurred in the East-South Central Division ($49,605).

“These data suggest industry payments in rheumatology have followed two distinct patterns, which have been observed in other medical subspecialties,” specifically, that many small payments are made to a large number of physicians, and large-value payments are made to a small number of physicians, the researchers noted.

The impact of small payments cannot be discounted, they said, “as even small gifts may affect behavior and are associated with prescribing patterns.” The impact of large payments on behavior and practice deserve further investigation, “but it is notable that a recent evaluation of rheumatology clinical practice guidelines identified substantial involvement from rheumatologists who had accepted large values of industry payments,” the researchers added.

Approximately half the total value of payments came from three companies: Bristol-Myers Squibb (20%), Abbvie (17%), and Pfizer (12%). Medications associated with the highest spending included Otezla, Humira, and Xeljanz.

Of note, the data showed that H.P. Acthar gel was among the top 10 agents for total payments, and “over 90% of rheumatologists who frequently prescribe H.P. Acthar gel have also received H.P. Acthar–related payments, raising the possibility that such payments have influenced prescribing behavior,” given the lack of high-quality evidence to support its use and the availability of less expensive alternatives, the researchers said.

The study findings were limited by several factors, including the focus only on general payments to rheumatologists, and the lack of external sources to verify payments, the researchers noted. “Most importantly, this was a descriptive study, and the degree to which payments have influenced physician behavior lies outside the scope of this work. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.”

Focus on collaborations that add value

The study is important because previous data on the magnitude of payments or payment patterns from pharmaceutical companies to practicing rheumatologists were limited, lead author Dr. Putman said in an interview.

“I was most surprised by some of the medications that received high values of payments,” he said. “Many payments were linked to medications that we use commonly and that have high-quality data supporting their use. That was not surprising, and you could imagine dollars spent on [interleukin]-23 or IL-17 inhibitors being used in a way that is valuable to other physicians or to patients with rheumatic diseases. On the other hand, some medications – most notably H.P. Acthar gel – have no high-quality data supporting their use, are used by a very small cadre of physicians, and are extraordinarily expensive. At least in my opinion, there is no world where payments linked to H.P. Acthar gel provide any benefit for physicians or patients.”

Dr. Putman said he expected that the patterns and the increases observed in the study are likely to continue.

“Ultimately, I have a somewhat nuanced view of financial conflicts of interest,” he said. “Collaborations between the pharmaceutical industry and rheumatologists have provided extraordinary value to our field. I think rheumatologists should be much more involved in some areas. At the same time, I think we should be much less involved in marketing drugs that provide little value to patients and great cost to society. H.P. Acthar Gel is the classic example of this, but there are others as well. I think future research should focus on how these payments influence behavior and should seek to identify areas where they result in low-value care.” Going forward, valuable collaborations between rheumatologists and the pharmaceutical industry should be encouraged, but collaborations without value should be discouraged, he said.
 

Industry payments serve no useful purpose

The findings “highlight the overarching concern regarding the ability of industry payments to adversely affect care quality within the specific context of rheumatology practice,” Aaron P. Mitchell, MD, of Memorial Sloan Kettering Cancer Center, New York, wrote in an accompanying editorial.

Dr. Mitchell emphasized several points, starting with the temporal trend showing an increase in industry payments beyond the rate of inflation that has not been universal across specialties. He also emphasized the “highly skewed distribution of payments,” with a large majority going to a relatively small number of rheumatologists. “This suggests an industry strategy of targeting ‘key opinion leaders,’ or KOLs, with higher payments,” and which was not surprising, as similar patterns have been seen in other specialties. Dr. Mitchell noted that 10 drugs accounted for more than half of the payments, and that “the unifying feature of these drugs is their high cost.”

“The picture of industry strategy that emerges from Putman et al. and other similar reports is that of intense, sustained KOL-focused marketing soon after the release of a new high-margin drug,” he wrote.

Despite the descriptive nature of the study, the findings have clinical implications based on other studies of the consequences of industry payments with respect to care quality, Dr. Mitchell said. “Hypothetically, industry spending to promote drugs to physicians could increase dissemination of new, superior drugs, improving patient outcomes.” However, physicians tend to opt for game-changing drugs without added incentive; “it is the less-innovative drugs that industry has to push harder.”

The practice of industry payments for physicians becomes even more difficult to rationalize given the potential for increased out-of-pocket costs and potentially avoidable toxicities for patients, Dr. Mitchell said. “Moreover, industry payments serve no unmet need; through our professional societies and other nonprofit sources, we physicians are fully capable of staying up-to-date on new treatments without relying on industry meals and sponsored events.”
 

Disclosure of payments is important

The study is important because it is essential to understand how public disclosure of industry payments influences financial relationship between the biomedical industry and physicians, said Amarnath Annapureddy, MD, a clinical fellow in cardiology at Yale University, New Haven, Conn., who has studied and written about industry payments to physicians.

Dr. Annapureddy said in an interview that he was surprised by how the study findings were opposite to the assumption that public disclosure would dissuade continuation of financial ties between physicians and industry. “This study showed payments increased over time rather than decreasing due to public disclosure.”

However, Dr. Annapureddy said that he was not surprised at how few physicians received the bulk of industry payments. “These physicians are considered to be ‘key opinion leaders’ who could influence practicing patterns of other physicians. These findings are similar to payment patterns for other specialties, including cardiology.

“So far, no study has evaluated factors that drive changes in industry payment patterns,” Dr. Annapureddy said. “I anticipate the patterns noted in this study will continue at least in the short term. If health care systems mandate physicians to disclose potential conflicts of interest to the patients, it may reduce payments.”

However, “unless, there is a major health policy mandate by government, I anticipate public disclosure of payments through the open payments program will not impact industry-physician ties,” he said. “This study has not evaluated impact of payments on prescribing practices. There are overwhelming data from several studies that showed payments influence physicians practicing patterns, whether it is prescribing a medication or implanting a device.” However, as for additional research, Dr. Annapureddy said that it would interesting to see a randomized trial to show whether the way physicians disclose their financial ties with patients would impact their practicing patterns.

The study received no outside funding. Dr. Putman was supported by a Rheumatology Research grant, but he and the other researchers had no financial conflicts to disclose. Dr. Mitchell disclosed a merit award from the nonprofit Conquer Cancer Foundation, for which the Foundation received financial support from Merck. Dr. Annapureddy had no financial conflicts to disclose.

Practicing rheumatologists in the United States received more than $220 million from pharmaceutical companies during 2014-2019, with payments increasing each year, according to findings from a descriptive study of the Centers for Medicare & Medicaid Services Open Payments Database.

Rheumatologists have identified conflicts of interest as an ethical concern, but the details of industry payments to rheumatologists have not been investigated, wrote Michael Putman, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues in Arthritis & Rheumatology. “Payments among rheumatologists may be of particular interest,” given their frequent prescription of expensive and primarily on-patent biologic and targeted disease-modifying antirheumatic drugs (DMARDs), the researchers said.

Over the 2014-2019 study period, 5,723 rheumatologists received a total of $221,254,966 from 1,610,668 payments. Of these, 3,416 (59%) received less than $5,000; 368 (6%) received more than $100,000, accounting for 78% of the total payments. The yearly value of the payments increased from $29,755,133 in 2014 to $46,308,926 in 2019, a 56% increase.

The payments to individual rheumatologists during the study period ranged from $8 to $5,612,254, with a median individual payment of $2,818. However, most (81%) of the payments were less than $25, and only 4% were more than $1,000.

Physicians who received more than $100,000 were significantly more likely to be paid speakers’ fees, consulting fees, and travel and lodging fees, but significantly less likely to receive payments for food and beverage than were those who received less than $100,000.

Overall, women made up 43% of the study population and received 34% of the total payments.

However, the median payment to male rheumatologists was significantly higher than the median payment to female rheumatologists ($3,732 vs. $2,084). Female rheumatologists were significantly more likely to receive payments for food and beverage and significantly less likely to receive speakers’ fees or travel and lodging coverage.

When the data were analyzed by state, California had the highest amount of total payments ($27,769,124), followed by New York and Texas, while Arizona had the highest spending per rheumatologist ($143,559). By region, based on U.S. Census divisions, the highest spending occurred in the Middle Atlantic Division ($46,327,351) and the highest per rheumatologist spending occurred in the East-South Central Division ($49,605).

“These data suggest industry payments in rheumatology have followed two distinct patterns, which have been observed in other medical subspecialties,” specifically, that many small payments are made to a large number of physicians, and large-value payments are made to a small number of physicians, the researchers noted.

The impact of small payments cannot be discounted, they said, “as even small gifts may affect behavior and are associated with prescribing patterns.” The impact of large payments on behavior and practice deserve further investigation, “but it is notable that a recent evaluation of rheumatology clinical practice guidelines identified substantial involvement from rheumatologists who had accepted large values of industry payments,” the researchers added.

Approximately half the total value of payments came from three companies: Bristol-Myers Squibb (20%), Abbvie (17%), and Pfizer (12%). Medications associated with the highest spending included Otezla, Humira, and Xeljanz.

Of note, the data showed that H.P. Acthar gel was among the top 10 agents for total payments, and “over 90% of rheumatologists who frequently prescribe H.P. Acthar gel have also received H.P. Acthar–related payments, raising the possibility that such payments have influenced prescribing behavior,” given the lack of high-quality evidence to support its use and the availability of less expensive alternatives, the researchers said.

The study findings were limited by several factors, including the focus only on general payments to rheumatologists, and the lack of external sources to verify payments, the researchers noted. “Most importantly, this was a descriptive study, and the degree to which payments have influenced physician behavior lies outside the scope of this work. Future studies should investigate the degree to which industry payments have influenced prescribing in the field of rheumatology.”

Focus on collaborations that add value

The study is important because previous data on the magnitude of payments or payment patterns from pharmaceutical companies to practicing rheumatologists were limited, lead author Dr. Putman said in an interview.

“I was most surprised by some of the medications that received high values of payments,” he said. “Many payments were linked to medications that we use commonly and that have high-quality data supporting their use. That was not surprising, and you could imagine dollars spent on [interleukin]-23 or IL-17 inhibitors being used in a way that is valuable to other physicians or to patients with rheumatic diseases. On the other hand, some medications – most notably H.P. Acthar gel – have no high-quality data supporting their use, are used by a very small cadre of physicians, and are extraordinarily expensive. At least in my opinion, there is no world where payments linked to H.P. Acthar gel provide any benefit for physicians or patients.”

Dr. Putman said he expected that the patterns and the increases observed in the study are likely to continue.

“Ultimately, I have a somewhat nuanced view of financial conflicts of interest,” he said. “Collaborations between the pharmaceutical industry and rheumatologists have provided extraordinary value to our field. I think rheumatologists should be much more involved in some areas. At the same time, I think we should be much less involved in marketing drugs that provide little value to patients and great cost to society. H.P. Acthar Gel is the classic example of this, but there are others as well. I think future research should focus on how these payments influence behavior and should seek to identify areas where they result in low-value care.” Going forward, valuable collaborations between rheumatologists and the pharmaceutical industry should be encouraged, but collaborations without value should be discouraged, he said.
 

Industry payments serve no useful purpose

The findings “highlight the overarching concern regarding the ability of industry payments to adversely affect care quality within the specific context of rheumatology practice,” Aaron P. Mitchell, MD, of Memorial Sloan Kettering Cancer Center, New York, wrote in an accompanying editorial.

Dr. Mitchell emphasized several points, starting with the temporal trend showing an increase in industry payments beyond the rate of inflation that has not been universal across specialties. He also emphasized the “highly skewed distribution of payments,” with a large majority going to a relatively small number of rheumatologists. “This suggests an industry strategy of targeting ‘key opinion leaders,’ or KOLs, with higher payments,” and which was not surprising, as similar patterns have been seen in other specialties. Dr. Mitchell noted that 10 drugs accounted for more than half of the payments, and that “the unifying feature of these drugs is their high cost.”

“The picture of industry strategy that emerges from Putman et al. and other similar reports is that of intense, sustained KOL-focused marketing soon after the release of a new high-margin drug,” he wrote.

Despite the descriptive nature of the study, the findings have clinical implications based on other studies of the consequences of industry payments with respect to care quality, Dr. Mitchell said. “Hypothetically, industry spending to promote drugs to physicians could increase dissemination of new, superior drugs, improving patient outcomes.” However, physicians tend to opt for game-changing drugs without added incentive; “it is the less-innovative drugs that industry has to push harder.”

The practice of industry payments for physicians becomes even more difficult to rationalize given the potential for increased out-of-pocket costs and potentially avoidable toxicities for patients, Dr. Mitchell said. “Moreover, industry payments serve no unmet need; through our professional societies and other nonprofit sources, we physicians are fully capable of staying up-to-date on new treatments without relying on industry meals and sponsored events.”
 

Disclosure of payments is important

The study is important because it is essential to understand how public disclosure of industry payments influences financial relationship between the biomedical industry and physicians, said Amarnath Annapureddy, MD, a clinical fellow in cardiology at Yale University, New Haven, Conn., who has studied and written about industry payments to physicians.

Dr. Annapureddy said in an interview that he was surprised by how the study findings were opposite to the assumption that public disclosure would dissuade continuation of financial ties between physicians and industry. “This study showed payments increased over time rather than decreasing due to public disclosure.”

However, Dr. Annapureddy said that he was not surprised at how few physicians received the bulk of industry payments. “These physicians are considered to be ‘key opinion leaders’ who could influence practicing patterns of other physicians. These findings are similar to payment patterns for other specialties, including cardiology.

“So far, no study has evaluated factors that drive changes in industry payment patterns,” Dr. Annapureddy said. “I anticipate the patterns noted in this study will continue at least in the short term. If health care systems mandate physicians to disclose potential conflicts of interest to the patients, it may reduce payments.”

However, “unless, there is a major health policy mandate by government, I anticipate public disclosure of payments through the open payments program will not impact industry-physician ties,” he said. “This study has not evaluated impact of payments on prescribing practices. There are overwhelming data from several studies that showed payments influence physicians practicing patterns, whether it is prescribing a medication or implanting a device.” However, as for additional research, Dr. Annapureddy said that it would interesting to see a randomized trial to show whether the way physicians disclose their financial ties with patients would impact their practicing patterns.

The study received no outside funding. Dr. Putman was supported by a Rheumatology Research grant, but he and the other researchers had no financial conflicts to disclose. Dr. Mitchell disclosed a merit award from the nonprofit Conquer Cancer Foundation, for which the Foundation received financial support from Merck. Dr. Annapureddy had no financial conflicts to disclose.

An influential, independent panel unanimously voted that aducanumab (Aduhelm) offers no benefit for patients with Alzheimer’s disease (AD), adding to growing opposition from medical experts to the Food and Drug Administration’s approval of this controversial drug.

The Institute for Clinical and Economic Review asked one of its expert panels, the California Technology Assessment Forum, to consider the available data about aducanumab and requested that members vote on whether there was sufficient evidence of a net benefit of aducanumab plus supportive care versus supportive care alone. All 15 panelists voted no.

Several panelists, including ICER President Steven D. Pearson, MD, talked about their personal experience with family members who have the disease.

There was universal agreement among the panelists that there is an urgent need for effective medications to treat the disease. However, the panel of clinicians and researchers also agreed that the evidence to date does not show that the drug helps patients with this debilitating disease.

Panelist Sei Lee, MD, a geriatrician at the University of California, San Francisco, said he lost his mother to AD 6 years ago. In addition to his clinical work, Dr. Lee has conducted research focused on improving the targeting of preventive AD interventions for older adults to maximize benefits and minimize harms.

Dr. Lee said he frequently felt completely overwhelmed by the challenges of his mother’s disease.

“I absolutely hear everyone who is saying we need an effective therapy for this,” Dr. Lee said.

Dr. Lee added that, as an experienced researcher who has weighed the aducanumab data, he saw no clear proof of a benefit that would outweigh the drug’s documented side effects in the two phase 3 trials of the drug. Those side effects include temporary brain swelling. Dr. Lee suggested that Biogen do more to address concerns about this side effect, saying it should not be ignored.

“There’s clearly substantial uncertainty” about aducanumab, Dr. Lee said. “If I had to guess, I think the data is stronger for net harm than it is for that benefit.”

Questions persist about the data Biogen used in support of aducanumab after announcing that the drug had failed in a dual-track phase 3 program.

In March 2019, it was announced that two phase 3 clinical trials, EMERGE and ENGAGE, were scrapped because of disappointing results. The trials were intended to show that aducanumab could slow progression of cognitive and functional impairment, as measured by changes in scores on the Clinical Dementia Rating–Sum of Boxes (CDR-SB).

However, in October 2019, there was an about-face – Biogen announced that, in one of the studies, there were positive findings for a subset of patients who received a higher dose of aducanumab.

No treatment benefit was observed in either the high- or low-dose arms at week 78 in the ENGAGE trial. In the EMERGE trial, however, there was a statistically significant difference in change from baseline in CDR-SB score in the high-dose arm (difference vs. placebo, –0.39; 95% confidence interval, –0.69 to –0.09) but not in the low-dose arm, ICER noted in a draft report.

Still, there are questions about whether this difference would translate into clinical benefit. “Although statistically significant, the change in CDR-SB score in the high-dose group was less than the 1- to 2-point change that has been suggested as a minimal clinically important difference,” ICER staff wrote.
 

More push back

Other influential organizations also remain skeptical.

On July 14, the Cleveland Clinic announced it would not use aducanumab at this time, following a staff review of the evidence. Physicians from the clinic could prescribe it to appropriate patients, who would receive their infusions at external facilities, a spokeswoman for the clinic told this news organization. The Cleveland Clinic said it will reevaluate this position as additional data become available.

In addition, as reported by the New York Times, the Mount Sinai Health System in New York also decided not to administer the drug.

The drug received accelerated approval from the FDA. That approval was conditional upon Biogen’s conducting further research by 2030 that demonstrates that the drug has clinical benefit.

On July 14, the executive committee of the American Neurological Association issued a statement asking for a speedier timeline.

The FDA should ensure that Biogen completes the required confirmatory study “as soon as possible, preferably within 3 years, to confirm or not whether clinical efficacy is observed,” the ANA executive committee wrote in the letter.

The ANA executive committee also criticized the FDA’s decision to allow Biogen to begin sales of the drug. In light of the clinical evidence available at this time, aducanumab “should not have been approved” in the first place, the ANA executive committee stated.

ICER will release a final report on aducanumab on August 5, drawing from the discussion at the meeting and the panel’s votes. The work of the Boston-based group is used by private insurers to inform medication coverage decisions.

Lawmakers have taken an interest in aducanumab. On July 12, two top Democrats in the U.S. House of Representatives released a letter that they had sent to Biogen as part of their investigation into how the FDA handled the aducanumab approval and Biogen’s pricing for the drug.

In the letter, House Energy and Commerce Chairman Frank Pallone Jr. (D-N.J.) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) wrote that they had “significant questions about the drug’s clinical benefit, and the steep $56,000 annual price tag.”

At the ICER meeting on July 15, Dr. Lee said patients with AD and their caregivers would benefit more from increased spending on supportive services, such as home health care.

“There’s so many things we could do” with money that Biogen may get for aducanumab, Dr. Lee said. “To spend it on a medication that is more likely to do more harm than help seems really ill advised.”

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

An influential, independent panel unanimously voted that aducanumab (Aduhelm) offers no benefit for patients with Alzheimer’s disease (AD), adding to growing opposition from medical experts to the Food and Drug Administration’s approval of this controversial drug.

The Institute for Clinical and Economic Review asked one of its expert panels, the California Technology Assessment Forum, to consider the available data about aducanumab and requested that members vote on whether there was sufficient evidence of a net benefit of aducanumab plus supportive care versus supportive care alone. All 15 panelists voted no.

Several panelists, including ICER President Steven D. Pearson, MD, talked about their personal experience with family members who have the disease.

There was universal agreement among the panelists that there is an urgent need for effective medications to treat the disease. However, the panel of clinicians and researchers also agreed that the evidence to date does not show that the drug helps patients with this debilitating disease.

Panelist Sei Lee, MD, a geriatrician at the University of California, San Francisco, said he lost his mother to AD 6 years ago. In addition to his clinical work, Dr. Lee has conducted research focused on improving the targeting of preventive AD interventions for older adults to maximize benefits and minimize harms.

Dr. Lee said he frequently felt completely overwhelmed by the challenges of his mother’s disease.

“I absolutely hear everyone who is saying we need an effective therapy for this,” Dr. Lee said.

Dr. Lee added that, as an experienced researcher who has weighed the aducanumab data, he saw no clear proof of a benefit that would outweigh the drug’s documented side effects in the two phase 3 trials of the drug. Those side effects include temporary brain swelling. Dr. Lee suggested that Biogen do more to address concerns about this side effect, saying it should not be ignored.

“There’s clearly substantial uncertainty” about aducanumab, Dr. Lee said. “If I had to guess, I think the data is stronger for net harm than it is for that benefit.”

Questions persist about the data Biogen used in support of aducanumab after announcing that the drug had failed in a dual-track phase 3 program.

In March 2019, it was announced that two phase 3 clinical trials, EMERGE and ENGAGE, were scrapped because of disappointing results. The trials were intended to show that aducanumab could slow progression of cognitive and functional impairment, as measured by changes in scores on the Clinical Dementia Rating–Sum of Boxes (CDR-SB).

However, in October 2019, there was an about-face – Biogen announced that, in one of the studies, there were positive findings for a subset of patients who received a higher dose of aducanumab.

No treatment benefit was observed in either the high- or low-dose arms at week 78 in the ENGAGE trial. In the EMERGE trial, however, there was a statistically significant difference in change from baseline in CDR-SB score in the high-dose arm (difference vs. placebo, –0.39; 95% confidence interval, –0.69 to –0.09) but not in the low-dose arm, ICER noted in a draft report.

Still, there are questions about whether this difference would translate into clinical benefit. “Although statistically significant, the change in CDR-SB score in the high-dose group was less than the 1- to 2-point change that has been suggested as a minimal clinically important difference,” ICER staff wrote.
 

More push back

Other influential organizations also remain skeptical.

On July 14, the Cleveland Clinic announced it would not use aducanumab at this time, following a staff review of the evidence. Physicians from the clinic could prescribe it to appropriate patients, who would receive their infusions at external facilities, a spokeswoman for the clinic told this news organization. The Cleveland Clinic said it will reevaluate this position as additional data become available.

In addition, as reported by the New York Times, the Mount Sinai Health System in New York also decided not to administer the drug.

The drug received accelerated approval from the FDA. That approval was conditional upon Biogen’s conducting further research by 2030 that demonstrates that the drug has clinical benefit.

On July 14, the executive committee of the American Neurological Association issued a statement asking for a speedier timeline.

The FDA should ensure that Biogen completes the required confirmatory study “as soon as possible, preferably within 3 years, to confirm or not whether clinical efficacy is observed,” the ANA executive committee wrote in the letter.

The ANA executive committee also criticized the FDA’s decision to allow Biogen to begin sales of the drug. In light of the clinical evidence available at this time, aducanumab “should not have been approved” in the first place, the ANA executive committee stated.

ICER will release a final report on aducanumab on August 5, drawing from the discussion at the meeting and the panel’s votes. The work of the Boston-based group is used by private insurers to inform medication coverage decisions.

Lawmakers have taken an interest in aducanumab. On July 12, two top Democrats in the U.S. House of Representatives released a letter that they had sent to Biogen as part of their investigation into how the FDA handled the aducanumab approval and Biogen’s pricing for the drug.

In the letter, House Energy and Commerce Chairman Frank Pallone Jr. (D-N.J.) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) wrote that they had “significant questions about the drug’s clinical benefit, and the steep $56,000 annual price tag.”

At the ICER meeting on July 15, Dr. Lee said patients with AD and their caregivers would benefit more from increased spending on supportive services, such as home health care.

“There’s so many things we could do” with money that Biogen may get for aducanumab, Dr. Lee said. “To spend it on a medication that is more likely to do more harm than help seems really ill advised.”

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

An influential, independent panel unanimously voted that aducanumab (Aduhelm) offers no benefit for patients with Alzheimer’s disease (AD), adding to growing opposition from medical experts to the Food and Drug Administration’s approval of this controversial drug.

The Institute for Clinical and Economic Review asked one of its expert panels, the California Technology Assessment Forum, to consider the available data about aducanumab and requested that members vote on whether there was sufficient evidence of a net benefit of aducanumab plus supportive care versus supportive care alone. All 15 panelists voted no.

Several panelists, including ICER President Steven D. Pearson, MD, talked about their personal experience with family members who have the disease.

There was universal agreement among the panelists that there is an urgent need for effective medications to treat the disease. However, the panel of clinicians and researchers also agreed that the evidence to date does not show that the drug helps patients with this debilitating disease.

Panelist Sei Lee, MD, a geriatrician at the University of California, San Francisco, said he lost his mother to AD 6 years ago. In addition to his clinical work, Dr. Lee has conducted research focused on improving the targeting of preventive AD interventions for older adults to maximize benefits and minimize harms.

Dr. Lee said he frequently felt completely overwhelmed by the challenges of his mother’s disease.

“I absolutely hear everyone who is saying we need an effective therapy for this,” Dr. Lee said.

Dr. Lee added that, as an experienced researcher who has weighed the aducanumab data, he saw no clear proof of a benefit that would outweigh the drug’s documented side effects in the two phase 3 trials of the drug. Those side effects include temporary brain swelling. Dr. Lee suggested that Biogen do more to address concerns about this side effect, saying it should not be ignored.

“There’s clearly substantial uncertainty” about aducanumab, Dr. Lee said. “If I had to guess, I think the data is stronger for net harm than it is for that benefit.”

Questions persist about the data Biogen used in support of aducanumab after announcing that the drug had failed in a dual-track phase 3 program.

In March 2019, it was announced that two phase 3 clinical trials, EMERGE and ENGAGE, were scrapped because of disappointing results. The trials were intended to show that aducanumab could slow progression of cognitive and functional impairment, as measured by changes in scores on the Clinical Dementia Rating–Sum of Boxes (CDR-SB).

However, in October 2019, there was an about-face – Biogen announced that, in one of the studies, there were positive findings for a subset of patients who received a higher dose of aducanumab.

No treatment benefit was observed in either the high- or low-dose arms at week 78 in the ENGAGE trial. In the EMERGE trial, however, there was a statistically significant difference in change from baseline in CDR-SB score in the high-dose arm (difference vs. placebo, –0.39; 95% confidence interval, –0.69 to –0.09) but not in the low-dose arm, ICER noted in a draft report.

Still, there are questions about whether this difference would translate into clinical benefit. “Although statistically significant, the change in CDR-SB score in the high-dose group was less than the 1- to 2-point change that has been suggested as a minimal clinically important difference,” ICER staff wrote.
 

More push back

Other influential organizations also remain skeptical.

On July 14, the Cleveland Clinic announced it would not use aducanumab at this time, following a staff review of the evidence. Physicians from the clinic could prescribe it to appropriate patients, who would receive their infusions at external facilities, a spokeswoman for the clinic told this news organization. The Cleveland Clinic said it will reevaluate this position as additional data become available.

In addition, as reported by the New York Times, the Mount Sinai Health System in New York also decided not to administer the drug.

The drug received accelerated approval from the FDA. That approval was conditional upon Biogen’s conducting further research by 2030 that demonstrates that the drug has clinical benefit.

On July 14, the executive committee of the American Neurological Association issued a statement asking for a speedier timeline.

The FDA should ensure that Biogen completes the required confirmatory study “as soon as possible, preferably within 3 years, to confirm or not whether clinical efficacy is observed,” the ANA executive committee wrote in the letter.

The ANA executive committee also criticized the FDA’s decision to allow Biogen to begin sales of the drug. In light of the clinical evidence available at this time, aducanumab “should not have been approved” in the first place, the ANA executive committee stated.

ICER will release a final report on aducanumab on August 5, drawing from the discussion at the meeting and the panel’s votes. The work of the Boston-based group is used by private insurers to inform medication coverage decisions.

Lawmakers have taken an interest in aducanumab. On July 12, two top Democrats in the U.S. House of Representatives released a letter that they had sent to Biogen as part of their investigation into how the FDA handled the aducanumab approval and Biogen’s pricing for the drug.

In the letter, House Energy and Commerce Chairman Frank Pallone Jr. (D-N.J.) and Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) wrote that they had “significant questions about the drug’s clinical benefit, and the steep $56,000 annual price tag.”

At the ICER meeting on July 15, Dr. Lee said patients with AD and their caregivers would benefit more from increased spending on supportive services, such as home health care.

“There’s so many things we could do” with money that Biogen may get for aducanumab, Dr. Lee said. “To spend it on a medication that is more likely to do more harm than help seems really ill advised.”

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.

Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.

In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.

The current study, led by Parakkal Deepak, MBBS, MS, and colleagues and published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.

The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.

The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.

Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.

At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.

Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).

Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.

“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.

The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.

This article was updated July 19, 2021.

In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.

Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.

In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.

The current study, led by Parakkal Deepak, MBBS, MS, and colleagues and published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.

The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.

The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.

Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.

At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.

Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).

Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.

“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.

The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.

This article was updated July 19, 2021.

In a real-world test, tofacitinib had a similar safety profile to what was seen in clinical trials. The majority of adverse events seen were infections, and few were serious; however, the study did find evidence of rare venous thromboembolism (VTE) in patients with preexisting risk factors, which suggests that precaution is warranted in this group.

Tofacitinib, a Janus kinase inhibitor, was approved by the Food and Drug Administration in 2018 for adults with moderate to severe ulcerative colitis (UC). Three phase 3 clinical trials and an open-label, long-term extension trial found that the drug was associated with increased infection rates and higher lipid levels.

In rheumatoid arthritis patients, an interim analysis of a safety clinical trial of twice-daily doses of 10 mg tofacitinib showed increased rates of pulmonary embolism and all-cause mortality, compared to treatment with a dose of 5 mg or a tumor necrosis factor antagonist. That finding led to a black box label warning against thrombosis.

The current study, led by Parakkal Deepak, MBBS, MS, and colleagues and published in Clinical Gastroenterology and Hepatology, included patients from six centers in the United States.

The findings suggest that patients should be counseled about the potential risk for herpes zoster (HZ) reactivation, especially older patients taking corticosteroids. The authors also recommended vaccination with an inactivated HZ vaccine. “Our data suggest a careful risk-benefit discussion before starting tofacitinib, especially in patients with preexisting risk factors for VTE, dose deescalation to the lowest clinically feasible dose, and monitoring for clinical signs of VTE, especially among those who continue on a dose of 10 mg twice a day,” the authors wrote.

The researchers followed 260 patients over a median of 6 months (median age, 38 years; 58.1% male; 71.9% non-Hispanic). Overall, 88.5% had previously received treatment with a biologic, most often an anti–TNF-alpha agent (76.5%). During follow-up, 15.7% experienced adverse events, most commonly infections (5.0%) and rash (3.5%). Joint pain (1.5%) and anemia (1.5%) also occurred. The incidence rate for any adverse event was 27.2 per 100 person-years. Adverse events occurred more often in older patients (mean age, 42 vs. 37 years; P = .02) and those who had not undergone previous anti-TNF therapy (63.4% vs 79.8%; P = .03). There was no association between concomitant steroid use and adverse events on univariate analysis. Of the overall cohort, 5.8% experienced a severe adverse event, with the most common being herpes zoster rash (26.7% of severe adverse events). Therapy was discontinued by 4.6%.

Five patients developed herpes zoster (3.29 per 100 person-years; 95% CI, 1.37-7.90). Risk factors for VTE were seen in 31.2% of the cohort, and two cases of VTE occurred during follow-up (1.32 per 100 person-years; 95% CI, 0.33-5.28), both in patients with extensive UC. There was no increased risk of complications following abdominal surgery.

At baseline, 38.4% had an abnormal lipid profile, and this increased to 48.3% following 8 weeks of treatment.

Overall, 45% of patients were anemic at baseline. Females experienced a significant improvement by week 26 (median hemoglobin level, 13.0 g/dL; interquartile range, 12.5-13.8), while a similar improvement occurred by week 52 in males (median hemoglobin level, 13.6 g/dL; IQR, 12.57-14.0). At 52 weeks, the mean increase in hemoglobin was 5% (IQR, 0%-11.1%). The increase was greater in females (7.7%; IQR, 4.2%-11.7%) than in males (2.1%; IQR, –0.5% to 11.3%).

Limitations of the study include its retrospective nature and that the tools by which data were collected could have missed some adverse events because they were not adequately captured in the treating clinician’s notes. However, the data trend similarly to a prospective study.

“In summary, we report safety signals on a real-world cohort of patients with UC initiated on tofacitinib in whom increasing age is a risk factor for AEs and consistent with recent reports of a dose-dependent risk of HZ reactivation and VTE events in patients with a risk factor for VTE on the 10-mg twice-daily dosing,” the authors concluded.

The study was funded by the American College of Gastroenterology, the Crohn’s and Colitis Foundation, the Givin’ it all for Guts Foundation, and the Lawrence C. Pakula, MD, Inflammatory Bowel Disease Research Innovation and Education Fund. The authors have financial ties with various pharmaceutical companies.

This article was updated July 19, 2021.

Meditation, yoga, breathing exercises, and other mindfulness activities can help children with attention-deficit/hyperactivity disorder, but it’s not just the kids who benefit.

When families of children with ADHD complete a mindfulness program together, a new study suggests, children and parents can profit, with potential boosts to self-control, self-compassion, and psychological symptoms.

The findings do not suggest children should ditch medication in favor of focusing on the present moment. Instead, the study adds to growing evidence that mindfulness can be a helpful tool along with other strategies for children and adults with ADHD, said John Mitchell, PhD, a psychologist at Duke University, Durham, N.C., who was not involved with the new study. Mindfulness might help families ease stress and improve quality of life.

“We talk about ADHD because one person has that diagnosis, but we don’t live in bubbles,” he said. “We’re all interconnected and impact one another. And having treatments that acknowledge that and measuring that in the scientific literature is pretty important.”

Mindfulness training, which has its roots in Eastern traditions, generally aims to teach people how to be present in the moment and let go of judgment. Over the last couple of decades, researchers working on depression and other conditions have gathered evidence that practicing mindfulness can help in a variety of ways, including with the self-regulation of attention and emotions. It didn’t take long for those findings to draw interest from researchers who study ADHD, Dr. Mitchell said.

Research on mindfulness for ADHD started with adults, and results have been encouraging, Dr. Mitchell said. People who complete a mindfulness program tend to show some improvement in focus, impulsivity, and hyperactivity, studies show. In one small pilot study, Dr. Mitchell and colleagues reported improvements in symptoms and executive function in adults with ADHD.

Studies with children have lagged behind, but recent work has been promising. When looking at data from a number of studies, researchers have found small reductions in inattentiveness, hyperactivity, and impulsivity in young people with ADHD. Several randomized, controlled trials have also shown a reduction in symptoms as rated by parents and teachers.
 

Greater understanding, acceptance

In related research, there was a noticed reduction in stress among parents who get mindfulness training that teaches them to listen with their full attention, accept and develop compassion for themselves and their children, and regulate themselves within the relationship with their kids.

Still, first-line treatment for children with ADHD usually includes a combination of medication, cognitive behavioral therapy, and education, even though those strategies don’t always work well for everyone, says Corina Greven, PhD, a psychologist at Radboud (the Netherlands) University Medical Centre and Karakter Child and Adolescent Psychiatry.

Despite suggestive results, the data on mindfulness remains murky, in part because early studies that looked at mindfulness training for children with ADHD have been small. Few trials of mindfulness treatment for ADHD, Dr. Greven said, have included parents.

To fill in some of the gaps, Dr. Greven and colleagues conducted a trial with 103 families who had a child with ADHD between ages 8 and 16. Half of the families were randomly assigned simply to continue care as usual, which included medication for most.

The other half continued their usual care and also took part in a program called MYMind, which used mindfulness-based cognitive therapy for children and mindful parenting training for parents.

Families attended 90-minute group sessions once a week for 8 weeks, with an extra session 2 months later. The mindfulness group also completed homework every day that took about 30-45 minutes for parents and 15 minutes for children. Homework included workbooks and guided meditations.

In the short term, the team reported, children who received the mindfulness intervention showed small improvements in ADHD symptoms, anxiety, autistic symptoms, and problems falling asleep. One-third children who received mindfulness training improved on measures of self-control, Dr. Greven added, compared with just 1 in 10 who got only their usual care.

Benefits were larger and longer-lasting for parents. Compared with parents who didn’t get mindfulness training, those assigned to the mindfulness group improved in self-control, self-compassion, depression, anxiety, stress, well-being, and their own ADHD symptoms. Given a large genetic component to the disorder, it is common for parents of children with ADHD to have a diagnosis or ADHD symptoms as well. In addition, Dr. Greven said, families who completed the mindfulness-based intervention reported improvements in their relationships as well as acceptance of ADHD.
 

A new therapy?

The findings suggest new potential treatment options for children with ADHD, and for their parents, Dr. Greven said, as well as a need to study the condition more broadly. “Although parents of children with ADHD often have elevated parenting stress, anxiety, or their own ADHD symptoms, usual interventions for children with ADHD do not typically target parental mental health,” she said. “As researchers, we need to go broader than just looking at whether an intervention reduces symptoms and include additional outcomes that families find important.”

It will take more research to find out who is most likely to benefit from mindfulness training and how long those benefits last, but the new study is a useful starting point, experts say.

“Mindfulness training had potentially short-term and long-term beneficial effects to children with ADHD and their parents,” says Samuel Wong, MD, director of the JC School of Public Health and Primary Care at the Chinese University of Hong Kong. He says mindfulness is more likely to become an add-on than a replacement for other kinds of therapies.

“Clinicians may consider combining or adding family-based mindfulness training with current practice for children with ADHD who have residual symptoms with their current treatment,” he said.

Mindfulness training may help with issues beyond the classic symptoms that come with ADHD, Dr. Mitchell said, helping make family life better overall, even when some features of the disorder don’t budge much.

“With this study in particular, we see that we have some pretty promising effects that there may be something that will be beneficial above and beyond the core 18 DSM symptoms,” he said. “This is an important study, because it’s going to be a basis for the continuing evolution of the scientific research on this topic. It’s something to feel excited about.”

A version of this article first appeared on WebMD.com.

Meditation, yoga, breathing exercises, and other mindfulness activities can help children with attention-deficit/hyperactivity disorder, but it’s not just the kids who benefit.

When families of children with ADHD complete a mindfulness program together, a new study suggests, children and parents can profit, with potential boosts to self-control, self-compassion, and psychological symptoms.

The findings do not suggest children should ditch medication in favor of focusing on the present moment. Instead, the study adds to growing evidence that mindfulness can be a helpful tool along with other strategies for children and adults with ADHD, said John Mitchell, PhD, a psychologist at Duke University, Durham, N.C., who was not involved with the new study. Mindfulness might help families ease stress and improve quality of life.

“We talk about ADHD because one person has that diagnosis, but we don’t live in bubbles,” he said. “We’re all interconnected and impact one another. And having treatments that acknowledge that and measuring that in the scientific literature is pretty important.”

Mindfulness training, which has its roots in Eastern traditions, generally aims to teach people how to be present in the moment and let go of judgment. Over the last couple of decades, researchers working on depression and other conditions have gathered evidence that practicing mindfulness can help in a variety of ways, including with the self-regulation of attention and emotions. It didn’t take long for those findings to draw interest from researchers who study ADHD, Dr. Mitchell said.

Research on mindfulness for ADHD started with adults, and results have been encouraging, Dr. Mitchell said. People who complete a mindfulness program tend to show some improvement in focus, impulsivity, and hyperactivity, studies show. In one small pilot study, Dr. Mitchell and colleagues reported improvements in symptoms and executive function in adults with ADHD.

Studies with children have lagged behind, but recent work has been promising. When looking at data from a number of studies, researchers have found small reductions in inattentiveness, hyperactivity, and impulsivity in young people with ADHD. Several randomized, controlled trials have also shown a reduction in symptoms as rated by parents and teachers.
 

Greater understanding, acceptance

In related research, there was a noticed reduction in stress among parents who get mindfulness training that teaches them to listen with their full attention, accept and develop compassion for themselves and their children, and regulate themselves within the relationship with their kids.

Still, first-line treatment for children with ADHD usually includes a combination of medication, cognitive behavioral therapy, and education, even though those strategies don’t always work well for everyone, says Corina Greven, PhD, a psychologist at Radboud (the Netherlands) University Medical Centre and Karakter Child and Adolescent Psychiatry.

Despite suggestive results, the data on mindfulness remains murky, in part because early studies that looked at mindfulness training for children with ADHD have been small. Few trials of mindfulness treatment for ADHD, Dr. Greven said, have included parents.

To fill in some of the gaps, Dr. Greven and colleagues conducted a trial with 103 families who had a child with ADHD between ages 8 and 16. Half of the families were randomly assigned simply to continue care as usual, which included medication for most.

The other half continued their usual care and also took part in a program called MYMind, which used mindfulness-based cognitive therapy for children and mindful parenting training for parents.

Families attended 90-minute group sessions once a week for 8 weeks, with an extra session 2 months later. The mindfulness group also completed homework every day that took about 30-45 minutes for parents and 15 minutes for children. Homework included workbooks and guided meditations.

In the short term, the team reported, children who received the mindfulness intervention showed small improvements in ADHD symptoms, anxiety, autistic symptoms, and problems falling asleep. One-third children who received mindfulness training improved on measures of self-control, Dr. Greven added, compared with just 1 in 10 who got only their usual care.

Benefits were larger and longer-lasting for parents. Compared with parents who didn’t get mindfulness training, those assigned to the mindfulness group improved in self-control, self-compassion, depression, anxiety, stress, well-being, and their own ADHD symptoms. Given a large genetic component to the disorder, it is common for parents of children with ADHD to have a diagnosis or ADHD symptoms as well. In addition, Dr. Greven said, families who completed the mindfulness-based intervention reported improvements in their relationships as well as acceptance of ADHD.
 

A new therapy?

The findings suggest new potential treatment options for children with ADHD, and for their parents, Dr. Greven said, as well as a need to study the condition more broadly. “Although parents of children with ADHD often have elevated parenting stress, anxiety, or their own ADHD symptoms, usual interventions for children with ADHD do not typically target parental mental health,” she said. “As researchers, we need to go broader than just looking at whether an intervention reduces symptoms and include additional outcomes that families find important.”

It will take more research to find out who is most likely to benefit from mindfulness training and how long those benefits last, but the new study is a useful starting point, experts say.

“Mindfulness training had potentially short-term and long-term beneficial effects to children with ADHD and their parents,” says Samuel Wong, MD, director of the JC School of Public Health and Primary Care at the Chinese University of Hong Kong. He says mindfulness is more likely to become an add-on than a replacement for other kinds of therapies.

“Clinicians may consider combining or adding family-based mindfulness training with current practice for children with ADHD who have residual symptoms with their current treatment,” he said.

Mindfulness training may help with issues beyond the classic symptoms that come with ADHD, Dr. Mitchell said, helping make family life better overall, even when some features of the disorder don’t budge much.

“With this study in particular, we see that we have some pretty promising effects that there may be something that will be beneficial above and beyond the core 18 DSM symptoms,” he said. “This is an important study, because it’s going to be a basis for the continuing evolution of the scientific research on this topic. It’s something to feel excited about.”

A version of this article first appeared on WebMD.com.

Meditation, yoga, breathing exercises, and other mindfulness activities can help children with attention-deficit/hyperactivity disorder, but it’s not just the kids who benefit.

When families of children with ADHD complete a mindfulness program together, a new study suggests, children and parents can profit, with potential boosts to self-control, self-compassion, and psychological symptoms.

The findings do not suggest children should ditch medication in favor of focusing on the present moment. Instead, the study adds to growing evidence that mindfulness can be a helpful tool along with other strategies for children and adults with ADHD, said John Mitchell, PhD, a psychologist at Duke University, Durham, N.C., who was not involved with the new study. Mindfulness might help families ease stress and improve quality of life.

“We talk about ADHD because one person has that diagnosis, but we don’t live in bubbles,” he said. “We’re all interconnected and impact one another. And having treatments that acknowledge that and measuring that in the scientific literature is pretty important.”

Mindfulness training, which has its roots in Eastern traditions, generally aims to teach people how to be present in the moment and let go of judgment. Over the last couple of decades, researchers working on depression and other conditions have gathered evidence that practicing mindfulness can help in a variety of ways, including with the self-regulation of attention and emotions. It didn’t take long for those findings to draw interest from researchers who study ADHD, Dr. Mitchell said.

Research on mindfulness for ADHD started with adults, and results have been encouraging, Dr. Mitchell said. People who complete a mindfulness program tend to show some improvement in focus, impulsivity, and hyperactivity, studies show. In one small pilot study, Dr. Mitchell and colleagues reported improvements in symptoms and executive function in adults with ADHD.

Studies with children have lagged behind, but recent work has been promising. When looking at data from a number of studies, researchers have found small reductions in inattentiveness, hyperactivity, and impulsivity in young people with ADHD. Several randomized, controlled trials have also shown a reduction in symptoms as rated by parents and teachers.
 

Greater understanding, acceptance

In related research, there was a noticed reduction in stress among parents who get mindfulness training that teaches them to listen with their full attention, accept and develop compassion for themselves and their children, and regulate themselves within the relationship with their kids.

Still, first-line treatment for children with ADHD usually includes a combination of medication, cognitive behavioral therapy, and education, even though those strategies don’t always work well for everyone, says Corina Greven, PhD, a psychologist at Radboud (the Netherlands) University Medical Centre and Karakter Child and Adolescent Psychiatry.

Despite suggestive results, the data on mindfulness remains murky, in part because early studies that looked at mindfulness training for children with ADHD have been small. Few trials of mindfulness treatment for ADHD, Dr. Greven said, have included parents.

To fill in some of the gaps, Dr. Greven and colleagues conducted a trial with 103 families who had a child with ADHD between ages 8 and 16. Half of the families were randomly assigned simply to continue care as usual, which included medication for most.

The other half continued their usual care and also took part in a program called MYMind, which used mindfulness-based cognitive therapy for children and mindful parenting training for parents.

Families attended 90-minute group sessions once a week for 8 weeks, with an extra session 2 months later. The mindfulness group also completed homework every day that took about 30-45 minutes for parents and 15 minutes for children. Homework included workbooks and guided meditations.

In the short term, the team reported, children who received the mindfulness intervention showed small improvements in ADHD symptoms, anxiety, autistic symptoms, and problems falling asleep. One-third children who received mindfulness training improved on measures of self-control, Dr. Greven added, compared with just 1 in 10 who got only their usual care.

Benefits were larger and longer-lasting for parents. Compared with parents who didn’t get mindfulness training, those assigned to the mindfulness group improved in self-control, self-compassion, depression, anxiety, stress, well-being, and their own ADHD symptoms. Given a large genetic component to the disorder, it is common for parents of children with ADHD to have a diagnosis or ADHD symptoms as well. In addition, Dr. Greven said, families who completed the mindfulness-based intervention reported improvements in their relationships as well as acceptance of ADHD.
 

A new therapy?

The findings suggest new potential treatment options for children with ADHD, and for their parents, Dr. Greven said, as well as a need to study the condition more broadly. “Although parents of children with ADHD often have elevated parenting stress, anxiety, or their own ADHD symptoms, usual interventions for children with ADHD do not typically target parental mental health,” she said. “As researchers, we need to go broader than just looking at whether an intervention reduces symptoms and include additional outcomes that families find important.”

It will take more research to find out who is most likely to benefit from mindfulness training and how long those benefits last, but the new study is a useful starting point, experts say.

“Mindfulness training had potentially short-term and long-term beneficial effects to children with ADHD and their parents,” says Samuel Wong, MD, director of the JC School of Public Health and Primary Care at the Chinese University of Hong Kong. He says mindfulness is more likely to become an add-on than a replacement for other kinds of therapies.

“Clinicians may consider combining or adding family-based mindfulness training with current practice for children with ADHD who have residual symptoms with their current treatment,” he said.

Mindfulness training may help with issues beyond the classic symptoms that come with ADHD, Dr. Mitchell said, helping make family life better overall, even when some features of the disorder don’t budge much.

“With this study in particular, we see that we have some pretty promising effects that there may be something that will be beneficial above and beyond the core 18 DSM symptoms,” he said. “This is an important study, because it’s going to be a basis for the continuing evolution of the scientific research on this topic. It’s something to feel excited about.”

A version of this article first appeared on WebMD.com.

U.S. Sen. Chuck Schumer, the Senate majority leader, is cosponsoring legislation that would decriminalize marijuana at the federal level.

VladK213/Getty Images

The Cannabis Administration & Opportunity Act would allow the federal government to regulate and tax marijuana sales for the first time and would stop the federal prosecution of people for possessing and selling the drug, The New York Times reported. States could still make their own marijuana laws, however.

The bill calls for using money raised by taxing marijuana to help poor people and communities of color that have been unduly affected by marijuana laws.

Arrests and convictions for nonviolent marijuana offenses would be automatically expunged, The New York Times reported.

“The War on Drugs has been a war on people – particularly people of color,” a draft of the bill said, adding that the bill “aims to end the decades of harm inflicted on communities of color by removing cannabis from the federal list of controlled substances and empowering states to implement their own cannabis laws.”

But passage of the bill is highly uncertain because of strong Republican opposition in the Senate, where Democrats hold a narrow majority, according to The New York Times.

President Biden has not said he supports such legislation.

Sen. Schumer signaled his intentions when he spoke on April 20, the unofficial holiday for marijuana smokers.

“Hopefully, the next time this unofficial holiday of 4/20 rolls around, our country will have made progress in addressing the massive overcriminalization of marijuana in a meaningful and comprehensive way,” he said at the time, the newspaper reported.

Cosponsors were U.S. Sen. Cory Booker of New Jersey and U.S. Sen. Ron Wyden of Oregon, chairman of the Senate Finance Committee.

A version of this article first appeared on WebMD.com.

U.S. Sen. Chuck Schumer, the Senate majority leader, is cosponsoring legislation that would decriminalize marijuana at the federal level.

VladK213/Getty Images

The Cannabis Administration & Opportunity Act would allow the federal government to regulate and tax marijuana sales for the first time and would stop the federal prosecution of people for possessing and selling the drug, The New York Times reported. States could still make their own marijuana laws, however.

The bill calls for using money raised by taxing marijuana to help poor people and communities of color that have been unduly affected by marijuana laws.

Arrests and convictions for nonviolent marijuana offenses would be automatically expunged, The New York Times reported.

“The War on Drugs has been a war on people – particularly people of color,” a draft of the bill said, adding that the bill “aims to end the decades of harm inflicted on communities of color by removing cannabis from the federal list of controlled substances and empowering states to implement their own cannabis laws.”

But passage of the bill is highly uncertain because of strong Republican opposition in the Senate, where Democrats hold a narrow majority, according to The New York Times.

President Biden has not said he supports such legislation.

Sen. Schumer signaled his intentions when he spoke on April 20, the unofficial holiday for marijuana smokers.

“Hopefully, the next time this unofficial holiday of 4/20 rolls around, our country will have made progress in addressing the massive overcriminalization of marijuana in a meaningful and comprehensive way,” he said at the time, the newspaper reported.

Cosponsors were U.S. Sen. Cory Booker of New Jersey and U.S. Sen. Ron Wyden of Oregon, chairman of the Senate Finance Committee.

A version of this article first appeared on WebMD.com.

U.S. Sen. Chuck Schumer, the Senate majority leader, is cosponsoring legislation that would decriminalize marijuana at the federal level.

VladK213/Getty Images

The Cannabis Administration & Opportunity Act would allow the federal government to regulate and tax marijuana sales for the first time and would stop the federal prosecution of people for possessing and selling the drug, The New York Times reported. States could still make their own marijuana laws, however.

The bill calls for using money raised by taxing marijuana to help poor people and communities of color that have been unduly affected by marijuana laws.

Arrests and convictions for nonviolent marijuana offenses would be automatically expunged, The New York Times reported.

“The War on Drugs has been a war on people – particularly people of color,” a draft of the bill said, adding that the bill “aims to end the decades of harm inflicted on communities of color by removing cannabis from the federal list of controlled substances and empowering states to implement their own cannabis laws.”

But passage of the bill is highly uncertain because of strong Republican opposition in the Senate, where Democrats hold a narrow majority, according to The New York Times.

President Biden has not said he supports such legislation.

Sen. Schumer signaled his intentions when he spoke on April 20, the unofficial holiday for marijuana smokers.

“Hopefully, the next time this unofficial holiday of 4/20 rolls around, our country will have made progress in addressing the massive overcriminalization of marijuana in a meaningful and comprehensive way,” he said at the time, the newspaper reported.

Cosponsors were U.S. Sen. Cory Booker of New Jersey and U.S. Sen. Ron Wyden of Oregon, chairman of the Senate Finance Committee.

A version of this article first appeared on WebMD.com.

Early treatment with low-molecular-weight heparin (LMWH) reduces the risk for death in patients with COVID-19, a retrospective cohort study shows.

Heparin could reduce the risk for blood clots, Andrea De Vito, MD, of the unit of infectious diseases at the University of Sassari, Italy, said during his online presentation of the findings at the 31st European Congress of Clinical Microbiology & Infectious Diseases.

“Several studies try to describe the role played by coagulopathies in COVID-19 death,” but the mechanism causing them is still unclear, Dr. De Vito explained.

Some guidelines have suggested heparin as a treatment for hospitalized COVID-19 patients, but few have looked at nonhospitalized patients. In fact, the National Institutes of Health discourages the use of heparin in nonhospitalized COVID-19 patients, and guidance for the home care of COVID-19 patients from the World Health Organization doesn’t mention heparin treatment at all, he said.

To examine the benefits of early heparin – whether administered at home or in the hospital – Dr. De Vito and colleagues looked at a cohort of older adults with COVID-19 who were evaluated or treated at an Italian university hospital.

“Some patients were hospitalized immediately after symptoms onset; other people preferred to call their general practitioner and started the treatment at home,” Dr. De Vito said in an interview. “Other people were hospitalized for worsening of symptoms later in the course of the disease.”

Of the 734 patients, 296 received heparin within 5 days of the onset of symptoms or a positive COVID-19 test. Of the remaining 438 patients, 196 received LMWH treatment later during the disease course, and the rest never received LMWH.

All patients who received early heparin were treated with LMWH 4,000 IU, or 6,000 IU if their body mass index was above 30 kg/m². This was reduced to 2,000 IU if estimated glomerular filtration rate (eGFR) dropped below 30 mL/min. None of the patients had previously received heparin.

Median age was slightly younger for patients who received early heparin than for those who did not (76.8 vs. 78.5 years).

Other demographic characteristics, such as sex and BMI, were similar in the two groups, as were rates of comorbidities, such as hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, kidney disease, and neurologic conditions. Also similar were the frequency of symptoms (such as fever, cough, and shortness of breath) and rates of treatment with remdesivir or steroids.

Rates of hospital admission were not significantly different between patients who received early heparin and those who did not (65% vs. 61%). There was also no significant difference in use of a venturi mask (35% vs. 28%), noninvasive ventilation (13% vs. 14%), or intubation (5% vs. 8%).

However, rates of death were significantly lower in patients who received early heparin than in those who did not (13% vs. 25%; P < .0001).

There was a trend toward shorter hospital stays for patients treated with early heparin, but the difference was not significant (median, 10 vs. 13 days; P = .08).

Researchers also conducted a separate analysis of 219 COVID-19 patients who received LMWH at home, regardless of when during their disease course they received it. These patients were significantly less likely to be hospitalized than were patients who did not receive LMWH at home (odds ratio, 0.2; P < .0001).

Comparatively, early heparin treatment had a greater effect on the risk for death and the risk for hospitalization than did other factors.

“Thromboemboli are a major complication of COVID. There is good consensus that hospitalized patients with COVID should receive anticoagulants prophylactically, although the best dose is being studied,” said Judy Stone, MD, an infectious disease physician and journalist who was not involved in the study.

“This study extends those findings of benefit from anticoagulants to nonhospitalized patients, with fewer deaths in those treated with low-molecular-weight heparin,” Dr. Stone told this news organization. “The major limitation is that the study is retrospective and observational. The next step would be to confirm these findings prospectively, randomizing a similar group to LMWH or no anticoagulation.”

Another limitation of the study is that some of the patients lived in nursing homes and might have received care from nurses that eliminated the need for hospitalization, Dr. De Vito added.

The study did not note any external funding. The authors have disclosed no relevant financial relationships. Dr. Stone is a member of the advisory committee for the C-Path CURE Drug Repurposing Collaboratory (CDRC) program and has written for Medscape.

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

Early treatment with low-molecular-weight heparin (LMWH) reduces the risk for death in patients with COVID-19, a retrospective cohort study shows.

Heparin could reduce the risk for blood clots, Andrea De Vito, MD, of the unit of infectious diseases at the University of Sassari, Italy, said during his online presentation of the findings at the 31st European Congress of Clinical Microbiology & Infectious Diseases.

“Several studies try to describe the role played by coagulopathies in COVID-19 death,” but the mechanism causing them is still unclear, Dr. De Vito explained.

Some guidelines have suggested heparin as a treatment for hospitalized COVID-19 patients, but few have looked at nonhospitalized patients. In fact, the National Institutes of Health discourages the use of heparin in nonhospitalized COVID-19 patients, and guidance for the home care of COVID-19 patients from the World Health Organization doesn’t mention heparin treatment at all, he said.

To examine the benefits of early heparin – whether administered at home or in the hospital – Dr. De Vito and colleagues looked at a cohort of older adults with COVID-19 who were evaluated or treated at an Italian university hospital.

“Some patients were hospitalized immediately after symptoms onset; other people preferred to call their general practitioner and started the treatment at home,” Dr. De Vito said in an interview. “Other people were hospitalized for worsening of symptoms later in the course of the disease.”

Of the 734 patients, 296 received heparin within 5 days of the onset of symptoms or a positive COVID-19 test. Of the remaining 438 patients, 196 received LMWH treatment later during the disease course, and the rest never received LMWH.

All patients who received early heparin were treated with LMWH 4,000 IU, or 6,000 IU if their body mass index was above 30 kg/m². This was reduced to 2,000 IU if estimated glomerular filtration rate (eGFR) dropped below 30 mL/min. None of the patients had previously received heparin.

Median age was slightly younger for patients who received early heparin than for those who did not (76.8 vs. 78.5 years).

Other demographic characteristics, such as sex and BMI, were similar in the two groups, as were rates of comorbidities, such as hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, kidney disease, and neurologic conditions. Also similar were the frequency of symptoms (such as fever, cough, and shortness of breath) and rates of treatment with remdesivir or steroids.

Rates of hospital admission were not significantly different between patients who received early heparin and those who did not (65% vs. 61%). There was also no significant difference in use of a venturi mask (35% vs. 28%), noninvasive ventilation (13% vs. 14%), or intubation (5% vs. 8%).

However, rates of death were significantly lower in patients who received early heparin than in those who did not (13% vs. 25%; P < .0001).

There was a trend toward shorter hospital stays for patients treated with early heparin, but the difference was not significant (median, 10 vs. 13 days; P = .08).

Researchers also conducted a separate analysis of 219 COVID-19 patients who received LMWH at home, regardless of when during their disease course they received it. These patients were significantly less likely to be hospitalized than were patients who did not receive LMWH at home (odds ratio, 0.2; P < .0001).

Comparatively, early heparin treatment had a greater effect on the risk for death and the risk for hospitalization than did other factors.

“Thromboemboli are a major complication of COVID. There is good consensus that hospitalized patients with COVID should receive anticoagulants prophylactically, although the best dose is being studied,” said Judy Stone, MD, an infectious disease physician and journalist who was not involved in the study.

“This study extends those findings of benefit from anticoagulants to nonhospitalized patients, with fewer deaths in those treated with low-molecular-weight heparin,” Dr. Stone told this news organization. “The major limitation is that the study is retrospective and observational. The next step would be to confirm these findings prospectively, randomizing a similar group to LMWH or no anticoagulation.”

Another limitation of the study is that some of the patients lived in nursing homes and might have received care from nurses that eliminated the need for hospitalization, Dr. De Vito added.

The study did not note any external funding. The authors have disclosed no relevant financial relationships. Dr. Stone is a member of the advisory committee for the C-Path CURE Drug Repurposing Collaboratory (CDRC) program and has written for Medscape.

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

Early treatment with low-molecular-weight heparin (LMWH) reduces the risk for death in patients with COVID-19, a retrospective cohort study shows.

Heparin could reduce the risk for blood clots, Andrea De Vito, MD, of the unit of infectious diseases at the University of Sassari, Italy, said during his online presentation of the findings at the 31st European Congress of Clinical Microbiology & Infectious Diseases.

“Several studies try to describe the role played by coagulopathies in COVID-19 death,” but the mechanism causing them is still unclear, Dr. De Vito explained.

Some guidelines have suggested heparin as a treatment for hospitalized COVID-19 patients, but few have looked at nonhospitalized patients. In fact, the National Institutes of Health discourages the use of heparin in nonhospitalized COVID-19 patients, and guidance for the home care of COVID-19 patients from the World Health Organization doesn’t mention heparin treatment at all, he said.

To examine the benefits of early heparin – whether administered at home or in the hospital – Dr. De Vito and colleagues looked at a cohort of older adults with COVID-19 who were evaluated or treated at an Italian university hospital.

“Some patients were hospitalized immediately after symptoms onset; other people preferred to call their general practitioner and started the treatment at home,” Dr. De Vito said in an interview. “Other people were hospitalized for worsening of symptoms later in the course of the disease.”

Of the 734 patients, 296 received heparin within 5 days of the onset of symptoms or a positive COVID-19 test. Of the remaining 438 patients, 196 received LMWH treatment later during the disease course, and the rest never received LMWH.

All patients who received early heparin were treated with LMWH 4,000 IU, or 6,000 IU if their body mass index was above 30 kg/m². This was reduced to 2,000 IU if estimated glomerular filtration rate (eGFR) dropped below 30 mL/min. None of the patients had previously received heparin.

Median age was slightly younger for patients who received early heparin than for those who did not (76.8 vs. 78.5 years).

Other demographic characteristics, such as sex and BMI, were similar in the two groups, as were rates of comorbidities, such as hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, kidney disease, and neurologic conditions. Also similar were the frequency of symptoms (such as fever, cough, and shortness of breath) and rates of treatment with remdesivir or steroids.

Rates of hospital admission were not significantly different between patients who received early heparin and those who did not (65% vs. 61%). There was also no significant difference in use of a venturi mask (35% vs. 28%), noninvasive ventilation (13% vs. 14%), or intubation (5% vs. 8%).

However, rates of death were significantly lower in patients who received early heparin than in those who did not (13% vs. 25%; P < .0001).

There was a trend toward shorter hospital stays for patients treated with early heparin, but the difference was not significant (median, 10 vs. 13 days; P = .08).

Researchers also conducted a separate analysis of 219 COVID-19 patients who received LMWH at home, regardless of when during their disease course they received it. These patients were significantly less likely to be hospitalized than were patients who did not receive LMWH at home (odds ratio, 0.2; P < .0001).

Comparatively, early heparin treatment had a greater effect on the risk for death and the risk for hospitalization than did other factors.

“Thromboemboli are a major complication of COVID. There is good consensus that hospitalized patients with COVID should receive anticoagulants prophylactically, although the best dose is being studied,” said Judy Stone, MD, an infectious disease physician and journalist who was not involved in the study.

“This study extends those findings of benefit from anticoagulants to nonhospitalized patients, with fewer deaths in those treated with low-molecular-weight heparin,” Dr. Stone told this news organization. “The major limitation is that the study is retrospective and observational. The next step would be to confirm these findings prospectively, randomizing a similar group to LMWH or no anticoagulation.”

Another limitation of the study is that some of the patients lived in nursing homes and might have received care from nurses that eliminated the need for hospitalization, Dr. De Vito added.

The study did not note any external funding. The authors have disclosed no relevant financial relationships. Dr. Stone is a member of the advisory committee for the C-Path CURE Drug Repurposing Collaboratory (CDRC) program and has written for Medscape.

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