MDedge Rheumatology

Combining D-limonene, a naturally occurring terpene in cannabis, with delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, may mitigate THC-induced anxiety, new data from a small study suggested.

Participants who inhaled vaporized D-limonene and THC reported significantly greater decreases in anxiogenic effects than did people who received either component alone or a placebo. Reductions were greater as the dose of the D-limonene was increased.

Investigators noted that the findings could have implications for the use of medicinal or recreational cannabis, which has increased in recent years due to state legalization efforts.

“People use cannabis to help reduce anxiety, depression, and posttraumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it,” senior investigator Ryan Vandrey, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, said in a news release.

“Our study demonstrates that D-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes,” he added.

The study was published online in Drug and Alcohol Dependence.
 

Entourage Theory

Cannabis legalization has opened the door to an increased range of medicinal and nonmedicinal uses, but its benefits can be limited by the anxiety and panic some people experience with its use, investigators noted.

Many cannabis plants have been bred to contain higher concentrations of THC, with some dispensaries selling cannabis with more than 20%-30% THC. The plants often include cannabidiol, “minor” cannabinoids, and terpenes, such as D-limonene.

Prior studies pointed to THC as the cause of acute behavioral and psychoactive effects some cannabis users experience. However, a new, untested theory, the “cannabis entourage effect theory,” suggested other components in cannabis, including D-limonene, may contribute to the anxiogenic symptoms.

“We were motivated by scientific publications that hypothesized D-limonene can attenuate the acute anxiogenic effects of cannabis, but for which empirical data did not exist,” Dr. Vandrey said.

Investigators designed a small double-blind, within-subjects crossover study of 20 healthy adults (median age, 26 years; 50% men). About half of participants were Caucasian/non-Hispanic, 30% African American/non-Hispanic, 10% Caucasian/Hispanic, and 10% Asian/non-Hispanic.

All participants completed nine outpatient drug administration sessions, during which they inhaled vaporized D-limonene alone (1 or 5 mg), THC alone (15 or 30 mg), the same doses of THC and D-limonene together, or placebo.

Primary outcomes included subjective drug effects, measured with the Drug Effect Questionnaire (DEQ) and the 20-item state subscale of the State-Trait Anxiety Inventory (STAI-S). Investigators also measured cognitive/psychomotor performance with the Digit Symbol Substitution Task (DSST) and the Paced Serial Addition Task.

Vital signs such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma D-limonene and THC concentrations were also tracked.

Participants’ responses were measured at baseline and then an additional nine times after initial exposure over the course of each 6-hour test session. Blood and urine samples were collected from participants before, during, and after each session.
 

First Evidence

There were no significant differences in outcomes between the D-limonene alone and placebo groups.

Receipt of 15- and 30-mg doses of THC alone was associated with subjective reports of acute cannabis exposure, including cognitive and physiological effects.

A treatment effect was observed for “anxious/nervous” (P < .01), “paranoid” (P < .01), and “heart racing” (P < .0001).

In planned comparisons, ratings of anxiety-like subjective effects qualitatively decreased as D-limonene dose increased, and concurrent administration of 30-mg THC plus 15-mg D-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” on the DEQ compared to 30 mg of THC alone (P < .05).

Findings were similar on the composite score of the STAI-S, and although planned comparisons did not reach the threshold for statistical significance, reductions in anxiety approached significance in the THC plus D-limonene group compared with the THC alone condition (P = .08). The combination group also reported significantly lower subjective ratings of unpleasant drug effects than the THC alone group (P = .03).

In particular, a main effect of treatment was found for the anxious/nervous category on the DEQ (P < .01), as well as the “paranoid” (P < .01) and heart racing (P < .0001) categories.

On the other hand, ratings of anxious/nervous and paranoid categories were significantly lower in the 30-mg THC plus 15-mg D-limonene vs the 30-mg THC alone condition (P < .05, for all).

As for cognition, following drug administration, a significant main effect of treatment was observed for the DSST (P < .05), but no significant differences between THC and THC plus D-limonene combination conditions or between D-limonene alone and placebo were detected.

There were no differences within each THC dose and between D-limonene alone versus placebo conditions. Moreover, there were no main effects of treatment found for SBP or DBP.

The combination condition produced significantly greater concentrations of THC than the THC alone condition (P < .05).

“This study provides the first evidence that there are chemical constituents found naturally in the cannabis plant that can reduce some of the adverse effects of using delta-9-THC,” Dr. Vandrey said.

Although the exact mechanism by which vaporized D-limonene counters the anxiogenic effects of THC is unclear, “our best guess is that D-limonene is producing an anxiolytic effect on its own that is not mediated by cannabinoid receptors,” Dr. Vandrey said.
 

Significant Impact

Commenting on the research, Joshua Lile, PhD, professor, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, noted that the study seems to be the first of its kind to study the influence of terpene on THC response.

The research “makes a significant impact on our field,” and is “among the few controlled clinical studies that have demonstrated interactions between THC and other cannabis constituents, supporting the validity of the ‘entourage’ effect,” said Dr. Lile, who was not involved with the current research.

“This work is particularly important, given the unfounded claims sometimes made by the cannabis industry regarding the effects of different cannabis products,” he added.

Also commenting on the study, Ziva Cooper, PhD, professor and director of the UCLA Center for Cannabis and Cannabinoids, University of California Los Angeles, said the findings “have direct implications for improving the safety of cannabis, whether it’s being used for medical or nonmedical purposes, especially in people and patients who do not have experience with cannabis, a group that is at high risk for experiencing anxiety after using cannabis.”

In addition, “an important aspect to this study is that the effects of limonene in reducing anxiety attributed to delta-9-THC were observed at higher concentrations (or doses) than those usually present in the plant,” Dr. Copper said. “This calls for further investigation into new cannabis formulations specifically designed to leverage the potential protective effects of the terpene.”

This research was supported by the National Institute on Drug Abuse. Dr. Vandrey served as a consultant or received honoraria from Mira1a Therapeutics, Inc.; Jazz Pharmaceuticals; Charlotte’s Web; Syqe Medical Ltd.; and WebMD. The other authors’ disclosures are listed on the original paper. Dr. Lile declared no relevant financial relationships. Dr. Cooper reported receiving study drug from Canopy Growth Corp and True Terpenes, study-related materials from Storz & Bickel, and research support from the National Institute on Drug Abuse, National Center for Complementary and Integrative Health, California Department of Cannabis Control, Center for Medicinal Cannabis Research, and California Highway Patrol.
 

A version of this article appeared on Medscape.com.

Combining D-limonene, a naturally occurring terpene in cannabis, with delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, may mitigate THC-induced anxiety, new data from a small study suggested.

Participants who inhaled vaporized D-limonene and THC reported significantly greater decreases in anxiogenic effects than did people who received either component alone or a placebo. Reductions were greater as the dose of the D-limonene was increased.

Investigators noted that the findings could have implications for the use of medicinal or recreational cannabis, which has increased in recent years due to state legalization efforts.

“People use cannabis to help reduce anxiety, depression, and posttraumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it,” senior investigator Ryan Vandrey, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, said in a news release.

“Our study demonstrates that D-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes,” he added.

The study was published online in Drug and Alcohol Dependence.
 

Entourage Theory

Cannabis legalization has opened the door to an increased range of medicinal and nonmedicinal uses, but its benefits can be limited by the anxiety and panic some people experience with its use, investigators noted.

Many cannabis plants have been bred to contain higher concentrations of THC, with some dispensaries selling cannabis with more than 20%-30% THC. The plants often include cannabidiol, “minor” cannabinoids, and terpenes, such as D-limonene.

Prior studies pointed to THC as the cause of acute behavioral and psychoactive effects some cannabis users experience. However, a new, untested theory, the “cannabis entourage effect theory,” suggested other components in cannabis, including D-limonene, may contribute to the anxiogenic symptoms.

“We were motivated by scientific publications that hypothesized D-limonene can attenuate the acute anxiogenic effects of cannabis, but for which empirical data did not exist,” Dr. Vandrey said.

Investigators designed a small double-blind, within-subjects crossover study of 20 healthy adults (median age, 26 years; 50% men). About half of participants were Caucasian/non-Hispanic, 30% African American/non-Hispanic, 10% Caucasian/Hispanic, and 10% Asian/non-Hispanic.

All participants completed nine outpatient drug administration sessions, during which they inhaled vaporized D-limonene alone (1 or 5 mg), THC alone (15 or 30 mg), the same doses of THC and D-limonene together, or placebo.

Primary outcomes included subjective drug effects, measured with the Drug Effect Questionnaire (DEQ) and the 20-item state subscale of the State-Trait Anxiety Inventory (STAI-S). Investigators also measured cognitive/psychomotor performance with the Digit Symbol Substitution Task (DSST) and the Paced Serial Addition Task.

Vital signs such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma D-limonene and THC concentrations were also tracked.

Participants’ responses were measured at baseline and then an additional nine times after initial exposure over the course of each 6-hour test session. Blood and urine samples were collected from participants before, during, and after each session.
 

First Evidence

There were no significant differences in outcomes between the D-limonene alone and placebo groups.

Receipt of 15- and 30-mg doses of THC alone was associated with subjective reports of acute cannabis exposure, including cognitive and physiological effects.

A treatment effect was observed for “anxious/nervous” (P < .01), “paranoid” (P < .01), and “heart racing” (P < .0001).

In planned comparisons, ratings of anxiety-like subjective effects qualitatively decreased as D-limonene dose increased, and concurrent administration of 30-mg THC plus 15-mg D-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” on the DEQ compared to 30 mg of THC alone (P < .05).

Findings were similar on the composite score of the STAI-S, and although planned comparisons did not reach the threshold for statistical significance, reductions in anxiety approached significance in the THC plus D-limonene group compared with the THC alone condition (P = .08). The combination group also reported significantly lower subjective ratings of unpleasant drug effects than the THC alone group (P = .03).

In particular, a main effect of treatment was found for the anxious/nervous category on the DEQ (P < .01), as well as the “paranoid” (P < .01) and heart racing (P < .0001) categories.

On the other hand, ratings of anxious/nervous and paranoid categories were significantly lower in the 30-mg THC plus 15-mg D-limonene vs the 30-mg THC alone condition (P < .05, for all).

As for cognition, following drug administration, a significant main effect of treatment was observed for the DSST (P < .05), but no significant differences between THC and THC plus D-limonene combination conditions or between D-limonene alone and placebo were detected.

There were no differences within each THC dose and between D-limonene alone versus placebo conditions. Moreover, there were no main effects of treatment found for SBP or DBP.

The combination condition produced significantly greater concentrations of THC than the THC alone condition (P < .05).

“This study provides the first evidence that there are chemical constituents found naturally in the cannabis plant that can reduce some of the adverse effects of using delta-9-THC,” Dr. Vandrey said.

Although the exact mechanism by which vaporized D-limonene counters the anxiogenic effects of THC is unclear, “our best guess is that D-limonene is producing an anxiolytic effect on its own that is not mediated by cannabinoid receptors,” Dr. Vandrey said.
 

Significant Impact

Commenting on the research, Joshua Lile, PhD, professor, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, noted that the study seems to be the first of its kind to study the influence of terpene on THC response.

The research “makes a significant impact on our field,” and is “among the few controlled clinical studies that have demonstrated interactions between THC and other cannabis constituents, supporting the validity of the ‘entourage’ effect,” said Dr. Lile, who was not involved with the current research.

“This work is particularly important, given the unfounded claims sometimes made by the cannabis industry regarding the effects of different cannabis products,” he added.

Also commenting on the study, Ziva Cooper, PhD, professor and director of the UCLA Center for Cannabis and Cannabinoids, University of California Los Angeles, said the findings “have direct implications for improving the safety of cannabis, whether it’s being used for medical or nonmedical purposes, especially in people and patients who do not have experience with cannabis, a group that is at high risk for experiencing anxiety after using cannabis.”

In addition, “an important aspect to this study is that the effects of limonene in reducing anxiety attributed to delta-9-THC were observed at higher concentrations (or doses) than those usually present in the plant,” Dr. Copper said. “This calls for further investigation into new cannabis formulations specifically designed to leverage the potential protective effects of the terpene.”

This research was supported by the National Institute on Drug Abuse. Dr. Vandrey served as a consultant or received honoraria from Mira1a Therapeutics, Inc.; Jazz Pharmaceuticals; Charlotte’s Web; Syqe Medical Ltd.; and WebMD. The other authors’ disclosures are listed on the original paper. Dr. Lile declared no relevant financial relationships. Dr. Cooper reported receiving study drug from Canopy Growth Corp and True Terpenes, study-related materials from Storz & Bickel, and research support from the National Institute on Drug Abuse, National Center for Complementary and Integrative Health, California Department of Cannabis Control, Center for Medicinal Cannabis Research, and California Highway Patrol.
 

A version of this article appeared on Medscape.com.

Combining D-limonene, a naturally occurring terpene in cannabis, with delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, may mitigate THC-induced anxiety, new data from a small study suggested.

Participants who inhaled vaporized D-limonene and THC reported significantly greater decreases in anxiogenic effects than did people who received either component alone or a placebo. Reductions were greater as the dose of the D-limonene was increased.

Investigators noted that the findings could have implications for the use of medicinal or recreational cannabis, which has increased in recent years due to state legalization efforts.

“People use cannabis to help reduce anxiety, depression, and posttraumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it,” senior investigator Ryan Vandrey, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, said in a news release.

“Our study demonstrates that D-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes,” he added.

The study was published online in Drug and Alcohol Dependence.
 

Entourage Theory

Cannabis legalization has opened the door to an increased range of medicinal and nonmedicinal uses, but its benefits can be limited by the anxiety and panic some people experience with its use, investigators noted.

Many cannabis plants have been bred to contain higher concentrations of THC, with some dispensaries selling cannabis with more than 20%-30% THC. The plants often include cannabidiol, “minor” cannabinoids, and terpenes, such as D-limonene.

Prior studies pointed to THC as the cause of acute behavioral and psychoactive effects some cannabis users experience. However, a new, untested theory, the “cannabis entourage effect theory,” suggested other components in cannabis, including D-limonene, may contribute to the anxiogenic symptoms.

“We were motivated by scientific publications that hypothesized D-limonene can attenuate the acute anxiogenic effects of cannabis, but for which empirical data did not exist,” Dr. Vandrey said.

Investigators designed a small double-blind, within-subjects crossover study of 20 healthy adults (median age, 26 years; 50% men). About half of participants were Caucasian/non-Hispanic, 30% African American/non-Hispanic, 10% Caucasian/Hispanic, and 10% Asian/non-Hispanic.

All participants completed nine outpatient drug administration sessions, during which they inhaled vaporized D-limonene alone (1 or 5 mg), THC alone (15 or 30 mg), the same doses of THC and D-limonene together, or placebo.

Primary outcomes included subjective drug effects, measured with the Drug Effect Questionnaire (DEQ) and the 20-item state subscale of the State-Trait Anxiety Inventory (STAI-S). Investigators also measured cognitive/psychomotor performance with the Digit Symbol Substitution Task (DSST) and the Paced Serial Addition Task.

Vital signs such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma D-limonene and THC concentrations were also tracked.

Participants’ responses were measured at baseline and then an additional nine times after initial exposure over the course of each 6-hour test session. Blood and urine samples were collected from participants before, during, and after each session.
 

First Evidence

There were no significant differences in outcomes between the D-limonene alone and placebo groups.

Receipt of 15- and 30-mg doses of THC alone was associated with subjective reports of acute cannabis exposure, including cognitive and physiological effects.

A treatment effect was observed for “anxious/nervous” (P < .01), “paranoid” (P < .01), and “heart racing” (P < .0001).

In planned comparisons, ratings of anxiety-like subjective effects qualitatively decreased as D-limonene dose increased, and concurrent administration of 30-mg THC plus 15-mg D-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” on the DEQ compared to 30 mg of THC alone (P < .05).

Findings were similar on the composite score of the STAI-S, and although planned comparisons did not reach the threshold for statistical significance, reductions in anxiety approached significance in the THC plus D-limonene group compared with the THC alone condition (P = .08). The combination group also reported significantly lower subjective ratings of unpleasant drug effects than the THC alone group (P = .03).

In particular, a main effect of treatment was found for the anxious/nervous category on the DEQ (P < .01), as well as the “paranoid” (P < .01) and heart racing (P < .0001) categories.

On the other hand, ratings of anxious/nervous and paranoid categories were significantly lower in the 30-mg THC plus 15-mg D-limonene vs the 30-mg THC alone condition (P < .05, for all).

As for cognition, following drug administration, a significant main effect of treatment was observed for the DSST (P < .05), but no significant differences between THC and THC plus D-limonene combination conditions or between D-limonene alone and placebo were detected.

There were no differences within each THC dose and between D-limonene alone versus placebo conditions. Moreover, there were no main effects of treatment found for SBP or DBP.

The combination condition produced significantly greater concentrations of THC than the THC alone condition (P < .05).

“This study provides the first evidence that there are chemical constituents found naturally in the cannabis plant that can reduce some of the adverse effects of using delta-9-THC,” Dr. Vandrey said.

Although the exact mechanism by which vaporized D-limonene counters the anxiogenic effects of THC is unclear, “our best guess is that D-limonene is producing an anxiolytic effect on its own that is not mediated by cannabinoid receptors,” Dr. Vandrey said.
 

Significant Impact

Commenting on the research, Joshua Lile, PhD, professor, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, noted that the study seems to be the first of its kind to study the influence of terpene on THC response.

The research “makes a significant impact on our field,” and is “among the few controlled clinical studies that have demonstrated interactions between THC and other cannabis constituents, supporting the validity of the ‘entourage’ effect,” said Dr. Lile, who was not involved with the current research.

“This work is particularly important, given the unfounded claims sometimes made by the cannabis industry regarding the effects of different cannabis products,” he added.

Also commenting on the study, Ziva Cooper, PhD, professor and director of the UCLA Center for Cannabis and Cannabinoids, University of California Los Angeles, said the findings “have direct implications for improving the safety of cannabis, whether it’s being used for medical or nonmedical purposes, especially in people and patients who do not have experience with cannabis, a group that is at high risk for experiencing anxiety after using cannabis.”

In addition, “an important aspect to this study is that the effects of limonene in reducing anxiety attributed to delta-9-THC were observed at higher concentrations (or doses) than those usually present in the plant,” Dr. Copper said. “This calls for further investigation into new cannabis formulations specifically designed to leverage the potential protective effects of the terpene.”

This research was supported by the National Institute on Drug Abuse. Dr. Vandrey served as a consultant or received honoraria from Mira1a Therapeutics, Inc.; Jazz Pharmaceuticals; Charlotte’s Web; Syqe Medical Ltd.; and WebMD. The other authors’ disclosures are listed on the original paper. Dr. Lile declared no relevant financial relationships. Dr. Cooper reported receiving study drug from Canopy Growth Corp and True Terpenes, study-related materials from Storz & Bickel, and research support from the National Institute on Drug Abuse, National Center for Complementary and Integrative Health, California Department of Cannabis Control, Center for Medicinal Cannabis Research, and California Highway Patrol.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When I was doing my nephrology training, I had an attending who would write notes that were, well, kind of funny. I remember one time we were seeing a patient whose first name was “Lucky.” He dryly opened his section of the consult note as follows: “This is a 56-year-old woman with an ironic name who presents with acute renal failure.”

As an exhausted renal fellow, I appreciated the bit of color amid the ongoing series of tragedies that was the consult service. But let’s be clear — writing like this in the medical record is not a good idea. It wasn’t a good idea then, when any record might end up disclosed during a malpractice suit, and it’s really not a good idea now, when patients have ready and automated access to all the notes we write about them.

And yet, worse language than that of my attending appears in hospital notes all the time; there is research about this. Specifically, I’m talking about language that does not have high clinical utility but telegraphs the biases of the person writing the note. This is known as “stigmatizing language” and it can be overt or subtle.

For example, a physician wrote “I listed several fictitious medication names and she reported she was taking them.”

This casts suspicions about the patient’s credibility, as does the more subtle statement, “he claims nicotine patches don’t work for him.” Stigmatizing language may cast the patient in a difficult light, like this note: “she persevered on the fact that ... ‘you wouldn’t understand.’ ”

This stuff creeps into our medical notes because doctors are human, not AI — at least not yet — and our frustrations and biases are real. But could those frustrations and biases lead to medical errors? Even deaths? Stay with me.

We are going to start by defining a very sick patient population: those admitted to the hospital and who, within 48 hours, have either been transferred to the intensive care unit or died. Because of the severity of illness in this population we’ve just defined, figuring out whether a diagnostic or other error was made would be extremely high yield; these can mean the difference between life and death.

In a letter appearing in JAMA Internal Medicine, researchers examined a group of more than 2300 patients just like this from 29 hospitals, scouring the medical records for evidence of these types of errors.

Nearly one in four (23.2%) had at least one diagnostic error, which could include a missed physical exam finding, failure to ask a key question on history taking, inadequate testing, and so on.

Understanding why we make these errors is clearly critical to improving care for these patients. The researchers hypothesized that stigmatizing language might lead to errors like this. For example, by demonstrating that you don’t find a patient credible, you may ignore statements that would help make a better diagnosis.

Just over 5% of these patients had evidence of stigmatizing language in their medical notes. Like earlier studies, this language was more common if the patient was Black or had unstable housing.

Critically, stigmatizing language was more likely to be found among those who had diagnostic errors — a rate of 8.2% vs 4.1%. After adjustment for factors like race, the presence of stigmatizing language was associated with roughly a doubling of the risk for diagnostic errors.

Now, I’m all for eliminating stigmatizing language from our medical notes. And, given the increased transparency of all medical notes these days, I expect that we’ll see less of this over time. But of course, the fact that a physician doesn’t write something that disparages the patient does not necessarily mean that they don’t retain that bias. That said, those comments have an effect on all the other team members who care for that patient as well; it sets a tone and can entrench an individual’s bias more broadly. We should strive to eliminate our biases when it comes to caring for patients. But perhaps the second best thing is to work to keep those biases to ourselves.
 

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When I was doing my nephrology training, I had an attending who would write notes that were, well, kind of funny. I remember one time we were seeing a patient whose first name was “Lucky.” He dryly opened his section of the consult note as follows: “This is a 56-year-old woman with an ironic name who presents with acute renal failure.”

As an exhausted renal fellow, I appreciated the bit of color amid the ongoing series of tragedies that was the consult service. But let’s be clear — writing like this in the medical record is not a good idea. It wasn’t a good idea then, when any record might end up disclosed during a malpractice suit, and it’s really not a good idea now, when patients have ready and automated access to all the notes we write about them.

And yet, worse language than that of my attending appears in hospital notes all the time; there is research about this. Specifically, I’m talking about language that does not have high clinical utility but telegraphs the biases of the person writing the note. This is known as “stigmatizing language” and it can be overt or subtle.

For example, a physician wrote “I listed several fictitious medication names and she reported she was taking them.”

This casts suspicions about the patient’s credibility, as does the more subtle statement, “he claims nicotine patches don’t work for him.” Stigmatizing language may cast the patient in a difficult light, like this note: “she persevered on the fact that ... ‘you wouldn’t understand.’ ”

This stuff creeps into our medical notes because doctors are human, not AI — at least not yet — and our frustrations and biases are real. But could those frustrations and biases lead to medical errors? Even deaths? Stay with me.

We are going to start by defining a very sick patient population: those admitted to the hospital and who, within 48 hours, have either been transferred to the intensive care unit or died. Because of the severity of illness in this population we’ve just defined, figuring out whether a diagnostic or other error was made would be extremely high yield; these can mean the difference between life and death.

In a letter appearing in JAMA Internal Medicine, researchers examined a group of more than 2300 patients just like this from 29 hospitals, scouring the medical records for evidence of these types of errors.

Nearly one in four (23.2%) had at least one diagnostic error, which could include a missed physical exam finding, failure to ask a key question on history taking, inadequate testing, and so on.

Understanding why we make these errors is clearly critical to improving care for these patients. The researchers hypothesized that stigmatizing language might lead to errors like this. For example, by demonstrating that you don’t find a patient credible, you may ignore statements that would help make a better diagnosis.

Just over 5% of these patients had evidence of stigmatizing language in their medical notes. Like earlier studies, this language was more common if the patient was Black or had unstable housing.

Critically, stigmatizing language was more likely to be found among those who had diagnostic errors — a rate of 8.2% vs 4.1%. After adjustment for factors like race, the presence of stigmatizing language was associated with roughly a doubling of the risk for diagnostic errors.

Now, I’m all for eliminating stigmatizing language from our medical notes. And, given the increased transparency of all medical notes these days, I expect that we’ll see less of this over time. But of course, the fact that a physician doesn’t write something that disparages the patient does not necessarily mean that they don’t retain that bias. That said, those comments have an effect on all the other team members who care for that patient as well; it sets a tone and can entrench an individual’s bias more broadly. We should strive to eliminate our biases when it comes to caring for patients. But perhaps the second best thing is to work to keep those biases to ourselves.
 

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When I was doing my nephrology training, I had an attending who would write notes that were, well, kind of funny. I remember one time we were seeing a patient whose first name was “Lucky.” He dryly opened his section of the consult note as follows: “This is a 56-year-old woman with an ironic name who presents with acute renal failure.”

As an exhausted renal fellow, I appreciated the bit of color amid the ongoing series of tragedies that was the consult service. But let’s be clear — writing like this in the medical record is not a good idea. It wasn’t a good idea then, when any record might end up disclosed during a malpractice suit, and it’s really not a good idea now, when patients have ready and automated access to all the notes we write about them.

And yet, worse language than that of my attending appears in hospital notes all the time; there is research about this. Specifically, I’m talking about language that does not have high clinical utility but telegraphs the biases of the person writing the note. This is known as “stigmatizing language” and it can be overt or subtle.

For example, a physician wrote “I listed several fictitious medication names and she reported she was taking them.”

This casts suspicions about the patient’s credibility, as does the more subtle statement, “he claims nicotine patches don’t work for him.” Stigmatizing language may cast the patient in a difficult light, like this note: “she persevered on the fact that ... ‘you wouldn’t understand.’ ”

This stuff creeps into our medical notes because doctors are human, not AI — at least not yet — and our frustrations and biases are real. But could those frustrations and biases lead to medical errors? Even deaths? Stay with me.

We are going to start by defining a very sick patient population: those admitted to the hospital and who, within 48 hours, have either been transferred to the intensive care unit or died. Because of the severity of illness in this population we’ve just defined, figuring out whether a diagnostic or other error was made would be extremely high yield; these can mean the difference between life and death.

In a letter appearing in JAMA Internal Medicine, researchers examined a group of more than 2300 patients just like this from 29 hospitals, scouring the medical records for evidence of these types of errors.

Nearly one in four (23.2%) had at least one diagnostic error, which could include a missed physical exam finding, failure to ask a key question on history taking, inadequate testing, and so on.

Understanding why we make these errors is clearly critical to improving care for these patients. The researchers hypothesized that stigmatizing language might lead to errors like this. For example, by demonstrating that you don’t find a patient credible, you may ignore statements that would help make a better diagnosis.

Just over 5% of these patients had evidence of stigmatizing language in their medical notes. Like earlier studies, this language was more common if the patient was Black or had unstable housing.

Critically, stigmatizing language was more likely to be found among those who had diagnostic errors — a rate of 8.2% vs 4.1%. After adjustment for factors like race, the presence of stigmatizing language was associated with roughly a doubling of the risk for diagnostic errors.

Now, I’m all for eliminating stigmatizing language from our medical notes. And, given the increased transparency of all medical notes these days, I expect that we’ll see less of this over time. But of course, the fact that a physician doesn’t write something that disparages the patient does not necessarily mean that they don’t retain that bias. That said, those comments have an effect on all the other team members who care for that patient as well; it sets a tone and can entrench an individual’s bias more broadly. We should strive to eliminate our biases when it comes to caring for patients. But perhaps the second best thing is to work to keep those biases to ourselves.
 

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.

In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.

University of Nebraska Medical Center

A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.

Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.

The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
 

Don’t Avoid Tapering But Take an Individualized Approach

Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.

“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.

Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.

In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.

“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.

Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.

“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.
 

Details of ARCTIC REWIND

The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.

There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.

Last year, 1-year results for the csDMARD arms were published in JAMA, and 1-year results for the TNF-inhibitor arms were reported in Annals of the Rheumatic Diseases.

At baseline, most patients across the three csDMARD groups (81%) had received methotrexate monotherapy. Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.

A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.

Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.

Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.

In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.

Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).

The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.

ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.

In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.

University of Nebraska Medical Center

A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.

Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.

The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
 

Don’t Avoid Tapering But Take an Individualized Approach

Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.

“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.

Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.

In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.

“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.

Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.

“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.
 

Details of ARCTIC REWIND

The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.

There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.

Last year, 1-year results for the csDMARD arms were published in JAMA, and 1-year results for the TNF-inhibitor arms were reported in Annals of the Rheumatic Diseases.

At baseline, most patients across the three csDMARD groups (81%) had received methotrexate monotherapy. Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.

A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.

Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.

Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.

In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.

Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).

The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.

ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with rheumatoid arthritis (RA) in remission who tapered and then fully stopped either conventional synthetic disease-modifying antirheumatic drug (csDMARD) or tumor necrosis factor (TNF)–inhibitor therapy experienced more disease flares than those who received stable dose treatment in an open-label, randomized trial.

In the 3-year trial, called ARCTIC REWIND, 80% of patients taking stable doses of only csMARDs remained flare-free compared with 38% in another treatment arm taking only csDMARDs who tapered to a half dose and then discontinued all after 1 year. In patients who continued to receive half-dose csDMARDs for the entire study period, 57% remained flare-free.

University of Nebraska Medical Center

A separate two treatment arms of the study that assessed the effect of tapering TNF-inhibitor treatment to withdrawal showed that only 25% of patients who tapered TNF inhibitor to withdrawal remained flare-free over 3 years compared with 85% who remained on a stable TNF-inhibitor dose.

Though the risk for flare was higher in both the half-dose csDMARD and drug-free groups, the results also suggested that tapering medication “could be a realistic option for some patients with rheumatoid arthritis in sustained remission on csDMARDs,” wrote Kaja Kjørholt, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases at Diakonhjemmet Hospital in Oslo, Norway, and colleagues.

The 3-year results for the csDMARD-only arms of the trial were published in The Lancet Rheumatology. The 3-year results of the TNF-inhibitor arms of the study were presented as an abstract at the annual meeting of the American College of Rheumatology (ACR).
 

Don’t Avoid Tapering But Take an Individualized Approach

Many rheumatologists will taper patients with RA in remission to lower doses of medication, but the protocols for this study do not reflect clinical practice, noted James R. O’Dell, MD, chief of the Division of Rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. He was not involved with the research.

“I don’t know of any rheumatologist who would ever think that it was a good idea to taper somebody completely off of all DMARDs,” he told this news organization. “The only surprise is that more of them didn’t flare,” he continued, though he suspected that more patients would flare if they were followed for more time. Rheumatologists also would take a much more individualized approach when tapering to lower doses, he added, and do so at a much slower rate than what was observed in this study.

Both the ACR and the European Alliance of Associations for Rheumatology recommendations for the management of RA stated that tapering DMARDs can be considered for patients who have sustained remission, but they do not mention discontinuing medication entirely.

In the TNF-inhibitor arms of the trial, the tapering group received a half dose of a TNF inhibitor for 4 months before stopping therapy entirely, which Dr. O’Dell noted was a large dip in too short a period.

“Nobody should be surprised that these people flared a lot,” he said. However, tapering to lower doses of a TNF inhibitor can be successful, he noted, adding that more than half of his patients taking a TNF inhibitor are on less than their original dose. Completely tapering off a TNF inhibitor is less common and depends on what other DMARDs a patient is taking, he said, and complete drug-free remission in this population is highly unlikely.

Dr. O’Dell emphasized that the takeaway from these results should not be to avoid tapering medication because of flare risk but instead a tailored approach — something that is not possible with a study protocol — is needed.

“We want our patients to have all the medicine they need and no more,” he said. “That sweet spot is different for each individual patient for how much TNF inhibition or how much conventional therapy they need. If we’re thoughtful about that in the clinic, we can find that sweet spot,” he said.
 

Details of ARCTIC REWIND

The open-label ARCTIC REWIND trial enrolled patients with RA in sustained remission, determined via Disease Activity Score (DAS), from 10 different hospitals in Norway. Researchers enrolled 160 patients in the csDMARD-only arms and randomized them to receive stable dose csDMARDs for 3 years or half-dose csDMARDs for 1 year, followed by complete withdrawal for the next 2 years; withdrawal of csDMARDs was only done in patients who had not had a flare during the first year. Participants had scheduled clinic visits every 4 months, and full-dose csDMARD therapy was resumed in patients who experienced disease flares.

There was a total of 99 patients randomized in the TNF-inhibitor arms to continue stable TNF-inhibitor therapy or to taper to a half dose for 4 months before discontinuing therapy. Like the csDMARD study, clinic visits occurred every 4 months, and full-dose therapy was resumed if a flare occurred. Patients taking a TNF inhibitor could also take a csDMARD as needed.

Last year, 1-year results for the csDMARD arms were published in JAMA, and 1-year results for the TNF-inhibitor arms were reported in Annals of the Rheumatic Diseases.

At baseline, most patients across the three csDMARD groups (81%) had received methotrexate monotherapy. Triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) was used in 13% of the stable-dose group, 7% of the half-dose group, and 8% of the half-dose tapering to withdrawal group. Seven individuals in the stable-dose group, three individuals in the half-dose group, and three individuals the half-dose tapering to withdrawal group used other mono/duo therapies.

A total of 139 participants in the csDMARD-only arms completed 3 years of follow-up, with 68 in the stable-dose group, 36 in the half-dose group, and 35 in the half-dose tapering to withdrawal group.

Compared with the stable-dose group, the risk for flare was more than four times higher in the half-dose tapering to withdrawal group (hazard ratio [HR], 4.2; 95% CI, 2.2-8.2) and about three times higher in the half-dose group (HR, 2.9; 95% CI, 1.5-5.9). The flare risk between the half dose and half-dose tapering to withdrawal group was not statistically significant.

Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. Comparing the last visit to baseline, 10 patients in the taper-to-withdrawal group (27%) had increased treatment — either by adding a biologic or increasing csDMARD dose — compared with one patient (3%) in the half-dose group and 11 patients (14%) in the stable-dose group. Adverse events were common across all three groups, though were highest in the tapering to withdrawal group.

In the TNF-inhibitor arms, a total of 80 patients completed the 3-year follow-up. By the end of 3 years, 75% of the tapering group experienced a disease flare compared with 15% of the stable TNF-inhibitor group. Most patients regained DAS remission status in the next clinic visit following a flare, the authors reported. During the study, 23% of the tapering group and 13% of the stable TNF-inhibitor group used systemic glucocorticoids. Four patients in the tapering group and two patients in the stable TNF-inhibitor group switched to another TNF inhibitor during the study. An additional two patients in the stable TNF-inhibitor group switched to a Janus kinase inhibitor during the 3-year study.

Adverse events were similar in both treatment groups, but serious adverse events were more common in the tapering group (21%) than in the stable-dose group (11%).

The authors concluded that the findings did not support tapering a TNF inhibitor to withdrawal for patients in sustained remission, but they noted that additional research is needed to identify which patients would fare better or worse tapering csDMARDs.

ARCTIC REWIND was funded by grants from The Research Council of Norway and The South-Eastern Norway Regional Health Authorities. Many of the authors disclosed financial ties to pharmaceutical companies. Dr. O’Dell disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The appeal of working from home is undeniable. It comes with no daily commute, casual dress, and the ability to manage work-life balance more effectively.

Telemedicine is often the first thing that comes to mind when physicians think about remote medical practice. In its traditional sense, telemedicine entails live video consults, replicating the in-person experience as closely as possible, minus the hands-on component. However, this format is just one of many types of virtual care presenting opportunities to practice medicine from home.

The scope and volume of such opportunities are expanding due to technology, regulatory shifts at the state and federal levels favoring remote healthcare, and a wider move toward remote work. Virtual practice options for physicians range from full-time employment to flexible part-time positions that can be used to earn supplementary income.

Just a few of those virtual options are:

Remote Patient Monitoring

Remote patient monitoring uses technology for tracking patient health data, applicable in real-time or asynchronously, through devices ranging from specialized monitors to consumer wearables. Data are securely transmitted to healthcare providers, enabling them to guide or make treatment choices remotely. This method has proven particularly valuable in managing chronic diseases where continuous monitoring can significantly affect outcomes.

Like standard telemedicine, remote patient monitoring offers flexibility, autonomy, and the ability to work from home. It is picking up steam across the healthcare industry, especially in critical care, surgery, post-acute care, and primary care, so there are opportunities for physicians across a variety of specialties.

Online Medication Management and Text-Based Consults

Gathering necessary information for patient care decisions often doesn’t require a direct, face-to-face visit in person or by telemedicine. Clinical data can be efficiently collected through online forms, HIPAA-compliant messaging, medical record reviews, and information gathered by staff.

An approach that uses all these sources enables effective medication management for stable chronic conditions (such as hypertension), as well as straightforward but simple acute issues (such as urinary tract infections). It also is useful for quick follow-ups with patients after starting new treatments, to address questions between visits, and to give them educational material.

Some medical practices and virtual healthcare corporations have made online medication management and text-based consults the center of their business model. Part-time positions with platforms that offer this type of care let physicians fit consultations into their schedule as time permits, without committing to scheduled appointments.

eConsults

Electronic consultations, or eConsults, facilitate collaboration among healthcare professionals about complex cases without direct patient interaction.

These services operate via online platforms that support asynchronous communication and often bypass the need for a traditional referral. Typically, a primary care provider submits a query that is then assigned to a specialist. Next, the specialist reviews the information and offers recommendations for the patient’s care plan.

Major eConsult platforms such as AristaMD and RubiconMD contract with healthcare systems and medical practices. Physicians can easily join the specialist panels of these companies and complete assigned consultations from their homes or offices, paid on a per-consult basis. They should check their employment contracts to make sure such independent contract work is allowed.

Phone-Only On-Call Positions

On-call rotations for after-hour care bring with them challenges in staffing and scheduling vacations. These challenges have helped trigger as-needed or per diem on-call roles, in which a physician provides recommendations and orders over the phone without needing to visit an office or a hospital.

Examples of workplaces that employ phone-only on-call physicians include smaller jails, mental health facilities, dialysis centers, long-term care facilities, and sporting groups or events needing back-up for on-site nurses or emergency medical technicians.

While these positions can sometimes be challenging for a physician to find, they are out there. They can be a fantastic option to earn additional income through low-stress clinical work performed from home.

Supervision of Nurse Practitioners (NPs) and Physician Assistants (PAs)

In states that mandate such physician oversight, it often be conducted remotely — depending on that state’s rules, the practice type, and the scope of services being provided. This remote option introduces part-time opportunities for physicians to oversee NPs and PAs without being in the medical office. Essentially, the doctor needs to be available for phone or email consultations, complete chart reviews, and meet regularly with the provider.

Remote supervision roles are available across various types of healthcare organizations and medical practices. There also are opportunities with insurers, many of which have established NP-run, in-home member assessment programs that require remote supervision by a doctor.

Remote Medical Directorships

Medical directors are a key part of the clinician team in a wide variety of healthcare settings requiring clinical protocol oversight, regulatory compliance, and guidance for other clinicians making treatment decisions. Many directorships do not require direct patient contact and therefore are conducive to remote work, given technologies such as electronic health record and secure messaging systems.

Organizations such as emergency medical service agencies, hospice services, med spas, blood and plasma donation centers, home health agencies, and substance use disorder treatment programs increasingly rely on remote medical directorships to meet legal requirements and accreditation standards.

Although these positions are often viewed as “nonclinical,” they carry significant clinical responsibilities. Examples are developing and reviewing treatment protocols, ensuring adherence to healthcare regulations, and sometimes intervening in complex patient cases or when adverse outcomes occur.

Keeping a Role in Patient Welfare

Clearly, working from home as a physician doesn’t have to mean taking on a nonclinical job. Beyond the options already mentioned, there are numerous others — for example, working as a medical monitor for clinical trials, in utilization management for insurance companies, or in conducting independent medical exams for insurance claims. While these roles don’t involve direct patient treatment, they require similar skills and affect the quality of care.

If such remote opportunities aren’t currently available in your workplace, consider approaching your management about trying them. You can make an effective argument that remote practice alternatives bring value to the organization through expanded patient care capabilities and potential cost savings.

Physicians who are experiencing burnout, seeking a career change, or interested in earning extra income should consider exploring more of the unconventional ways that they can practice medicine.

A version of this article appeared on Medscape.com.

The appeal of working from home is undeniable. It comes with no daily commute, casual dress, and the ability to manage work-life balance more effectively.

Telemedicine is often the first thing that comes to mind when physicians think about remote medical practice. In its traditional sense, telemedicine entails live video consults, replicating the in-person experience as closely as possible, minus the hands-on component. However, this format is just one of many types of virtual care presenting opportunities to practice medicine from home.

The scope and volume of such opportunities are expanding due to technology, regulatory shifts at the state and federal levels favoring remote healthcare, and a wider move toward remote work. Virtual practice options for physicians range from full-time employment to flexible part-time positions that can be used to earn supplementary income.

Just a few of those virtual options are:

Remote Patient Monitoring

Remote patient monitoring uses technology for tracking patient health data, applicable in real-time or asynchronously, through devices ranging from specialized monitors to consumer wearables. Data are securely transmitted to healthcare providers, enabling them to guide or make treatment choices remotely. This method has proven particularly valuable in managing chronic diseases where continuous monitoring can significantly affect outcomes.

Like standard telemedicine, remote patient monitoring offers flexibility, autonomy, and the ability to work from home. It is picking up steam across the healthcare industry, especially in critical care, surgery, post-acute care, and primary care, so there are opportunities for physicians across a variety of specialties.

Online Medication Management and Text-Based Consults

Gathering necessary information for patient care decisions often doesn’t require a direct, face-to-face visit in person or by telemedicine. Clinical data can be efficiently collected through online forms, HIPAA-compliant messaging, medical record reviews, and information gathered by staff.

An approach that uses all these sources enables effective medication management for stable chronic conditions (such as hypertension), as well as straightforward but simple acute issues (such as urinary tract infections). It also is useful for quick follow-ups with patients after starting new treatments, to address questions between visits, and to give them educational material.

Some medical practices and virtual healthcare corporations have made online medication management and text-based consults the center of their business model. Part-time positions with platforms that offer this type of care let physicians fit consultations into their schedule as time permits, without committing to scheduled appointments.

eConsults

Electronic consultations, or eConsults, facilitate collaboration among healthcare professionals about complex cases without direct patient interaction.

These services operate via online platforms that support asynchronous communication and often bypass the need for a traditional referral. Typically, a primary care provider submits a query that is then assigned to a specialist. Next, the specialist reviews the information and offers recommendations for the patient’s care plan.

Major eConsult platforms such as AristaMD and RubiconMD contract with healthcare systems and medical practices. Physicians can easily join the specialist panels of these companies and complete assigned consultations from their homes or offices, paid on a per-consult basis. They should check their employment contracts to make sure such independent contract work is allowed.

Phone-Only On-Call Positions

On-call rotations for after-hour care bring with them challenges in staffing and scheduling vacations. These challenges have helped trigger as-needed or per diem on-call roles, in which a physician provides recommendations and orders over the phone without needing to visit an office or a hospital.

Examples of workplaces that employ phone-only on-call physicians include smaller jails, mental health facilities, dialysis centers, long-term care facilities, and sporting groups or events needing back-up for on-site nurses or emergency medical technicians.

While these positions can sometimes be challenging for a physician to find, they are out there. They can be a fantastic option to earn additional income through low-stress clinical work performed from home.

Supervision of Nurse Practitioners (NPs) and Physician Assistants (PAs)

In states that mandate such physician oversight, it often be conducted remotely — depending on that state’s rules, the practice type, and the scope of services being provided. This remote option introduces part-time opportunities for physicians to oversee NPs and PAs without being in the medical office. Essentially, the doctor needs to be available for phone or email consultations, complete chart reviews, and meet regularly with the provider.

Remote supervision roles are available across various types of healthcare organizations and medical practices. There also are opportunities with insurers, many of which have established NP-run, in-home member assessment programs that require remote supervision by a doctor.

Remote Medical Directorships

Medical directors are a key part of the clinician team in a wide variety of healthcare settings requiring clinical protocol oversight, regulatory compliance, and guidance for other clinicians making treatment decisions. Many directorships do not require direct patient contact and therefore are conducive to remote work, given technologies such as electronic health record and secure messaging systems.

Organizations such as emergency medical service agencies, hospice services, med spas, blood and plasma donation centers, home health agencies, and substance use disorder treatment programs increasingly rely on remote medical directorships to meet legal requirements and accreditation standards.

Although these positions are often viewed as “nonclinical,” they carry significant clinical responsibilities. Examples are developing and reviewing treatment protocols, ensuring adherence to healthcare regulations, and sometimes intervening in complex patient cases or when adverse outcomes occur.

Keeping a Role in Patient Welfare

Clearly, working from home as a physician doesn’t have to mean taking on a nonclinical job. Beyond the options already mentioned, there are numerous others — for example, working as a medical monitor for clinical trials, in utilization management for insurance companies, or in conducting independent medical exams for insurance claims. While these roles don’t involve direct patient treatment, they require similar skills and affect the quality of care.

If such remote opportunities aren’t currently available in your workplace, consider approaching your management about trying them. You can make an effective argument that remote practice alternatives bring value to the organization through expanded patient care capabilities and potential cost savings.

Physicians who are experiencing burnout, seeking a career change, or interested in earning extra income should consider exploring more of the unconventional ways that they can practice medicine.

A version of this article appeared on Medscape.com.

The appeal of working from home is undeniable. It comes with no daily commute, casual dress, and the ability to manage work-life balance more effectively.

Telemedicine is often the first thing that comes to mind when physicians think about remote medical practice. In its traditional sense, telemedicine entails live video consults, replicating the in-person experience as closely as possible, minus the hands-on component. However, this format is just one of many types of virtual care presenting opportunities to practice medicine from home.

The scope and volume of such opportunities are expanding due to technology, regulatory shifts at the state and federal levels favoring remote healthcare, and a wider move toward remote work. Virtual practice options for physicians range from full-time employment to flexible part-time positions that can be used to earn supplementary income.

Just a few of those virtual options are:

Remote Patient Monitoring

Remote patient monitoring uses technology for tracking patient health data, applicable in real-time or asynchronously, through devices ranging from specialized monitors to consumer wearables. Data are securely transmitted to healthcare providers, enabling them to guide or make treatment choices remotely. This method has proven particularly valuable in managing chronic diseases where continuous monitoring can significantly affect outcomes.

Like standard telemedicine, remote patient monitoring offers flexibility, autonomy, and the ability to work from home. It is picking up steam across the healthcare industry, especially in critical care, surgery, post-acute care, and primary care, so there are opportunities for physicians across a variety of specialties.

Online Medication Management and Text-Based Consults

Gathering necessary information for patient care decisions often doesn’t require a direct, face-to-face visit in person or by telemedicine. Clinical data can be efficiently collected through online forms, HIPAA-compliant messaging, medical record reviews, and information gathered by staff.

An approach that uses all these sources enables effective medication management for stable chronic conditions (such as hypertension), as well as straightforward but simple acute issues (such as urinary tract infections). It also is useful for quick follow-ups with patients after starting new treatments, to address questions between visits, and to give them educational material.

Some medical practices and virtual healthcare corporations have made online medication management and text-based consults the center of their business model. Part-time positions with platforms that offer this type of care let physicians fit consultations into their schedule as time permits, without committing to scheduled appointments.

eConsults

Electronic consultations, or eConsults, facilitate collaboration among healthcare professionals about complex cases without direct patient interaction.

These services operate via online platforms that support asynchronous communication and often bypass the need for a traditional referral. Typically, a primary care provider submits a query that is then assigned to a specialist. Next, the specialist reviews the information and offers recommendations for the patient’s care plan.

Major eConsult platforms such as AristaMD and RubiconMD contract with healthcare systems and medical practices. Physicians can easily join the specialist panels of these companies and complete assigned consultations from their homes or offices, paid on a per-consult basis. They should check their employment contracts to make sure such independent contract work is allowed.

Phone-Only On-Call Positions

On-call rotations for after-hour care bring with them challenges in staffing and scheduling vacations. These challenges have helped trigger as-needed or per diem on-call roles, in which a physician provides recommendations and orders over the phone without needing to visit an office or a hospital.

Examples of workplaces that employ phone-only on-call physicians include smaller jails, mental health facilities, dialysis centers, long-term care facilities, and sporting groups or events needing back-up for on-site nurses or emergency medical technicians.

While these positions can sometimes be challenging for a physician to find, they are out there. They can be a fantastic option to earn additional income through low-stress clinical work performed from home.

Supervision of Nurse Practitioners (NPs) and Physician Assistants (PAs)

In states that mandate such physician oversight, it often be conducted remotely — depending on that state’s rules, the practice type, and the scope of services being provided. This remote option introduces part-time opportunities for physicians to oversee NPs and PAs without being in the medical office. Essentially, the doctor needs to be available for phone or email consultations, complete chart reviews, and meet regularly with the provider.

Remote supervision roles are available across various types of healthcare organizations and medical practices. There also are opportunities with insurers, many of which have established NP-run, in-home member assessment programs that require remote supervision by a doctor.

Remote Medical Directorships

Medical directors are a key part of the clinician team in a wide variety of healthcare settings requiring clinical protocol oversight, regulatory compliance, and guidance for other clinicians making treatment decisions. Many directorships do not require direct patient contact and therefore are conducive to remote work, given technologies such as electronic health record and secure messaging systems.

Organizations such as emergency medical service agencies, hospice services, med spas, blood and plasma donation centers, home health agencies, and substance use disorder treatment programs increasingly rely on remote medical directorships to meet legal requirements and accreditation standards.

Although these positions are often viewed as “nonclinical,” they carry significant clinical responsibilities. Examples are developing and reviewing treatment protocols, ensuring adherence to healthcare regulations, and sometimes intervening in complex patient cases or when adverse outcomes occur.

Keeping a Role in Patient Welfare

Clearly, working from home as a physician doesn’t have to mean taking on a nonclinical job. Beyond the options already mentioned, there are numerous others — for example, working as a medical monitor for clinical trials, in utilization management for insurance companies, or in conducting independent medical exams for insurance claims. While these roles don’t involve direct patient treatment, they require similar skills and affect the quality of care.

If such remote opportunities aren’t currently available in your workplace, consider approaching your management about trying them. You can make an effective argument that remote practice alternatives bring value to the organization through expanded patient care capabilities and potential cost savings.

Physicians who are experiencing burnout, seeking a career change, or interested in earning extra income should consider exploring more of the unconventional ways that they can practice medicine.

A version of this article appeared on Medscape.com.

TOPLINE:

Tocilizumab administration results in high remission rates in adult-onset Still’s disease (AOSD), but the recurrence rate increases on tocilizumab discontinuation, with a longer tocilizumab interval and lower prednisolone dose being critical for successful tocilizumab withdrawal.

METHODOLOGY:

• Tocilizumab is effective in reducing systemic inflammation and lowering glucocorticoid doses in patients with AOSD; however, the possibility of tocilizumab withdrawal has not been explored.
• This retrospective study assessed whether tocilizumab can be discontinued after achieving remission in 48 patients with AOSD.
• The systemic feature score, Pouchot score, and modified Pouchot score were used to evaluate the disease activity.
• Remission was characterized by the absence of symptoms related to Still’s disease, normal levels of erythrocyte sedimentation rate and C-reactive protein, and absence of treatment intensification requirement.
• Recurrence after tocilizumab discontinuation was defined as a disease flare with AOSD treatment intensification that necessitated either a ≥ 1.5-fold increase in glucocorticoid dosage and/or the initiation of a biologic agent.

TAKEAWAY:

• Over a median observation period of 5.1 years, 38 (79.2%) patients achieved remission at 6 months, of which 13 discontinued tocilizumab and the remaining 25 continued it.
• Among patients who discontinued tocilizumab on achieving remission, recurrence was noted in 50% within a year, typically after a mean period of 5.5 months after discontinuation.
• Patients in remission with longer tocilizumab intervals (> 14 days; P < .0002) or lower prednisolone doses (< 7 mg/d; P = .001) at the time of tocilizumab discontinuation showed better recurrence-free rates than those without.
• The duration of tocilizumab use, systemic feature score, and serum ferritin levels at tocilizumab discontinuation were not significantly different between patients who experienced recurrence and those who did not.

IN PRACTICE:

“Stable conditions with extended intervals of tocilizumab administration and very low doses of concomitant glucocorticoids are essential for successful discontinuation,” the authors wrote.

SOURCE:

The study was led by Hiroya Tamai, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, and published online in Rheumatology (Oxford).

LIMITATIONS:

The study was limited by its retrospective study design and a small sample size. Moreover, there could have been a selection bias as the attending physicians could use their discretion to initiate or stop tocilizumab treatment. The absence of a universally agreed-upon definition for remission or recurrence in AOSD made comparing the findings of this study with those of others challenging.

DISCLOSURES:

This study did not receive any specific funding from any bodies in public, commercial, or nonprofit sectors. Some of the authors reported receiving honoraria and research support from various pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Tocilizumab administration results in high remission rates in adult-onset Still’s disease (AOSD), but the recurrence rate increases on tocilizumab discontinuation, with a longer tocilizumab interval and lower prednisolone dose being critical for successful tocilizumab withdrawal.

METHODOLOGY:

• Tocilizumab is effective in reducing systemic inflammation and lowering glucocorticoid doses in patients with AOSD; however, the possibility of tocilizumab withdrawal has not been explored.
• This retrospective study assessed whether tocilizumab can be discontinued after achieving remission in 48 patients with AOSD.
• The systemic feature score, Pouchot score, and modified Pouchot score were used to evaluate the disease activity.
• Remission was characterized by the absence of symptoms related to Still’s disease, normal levels of erythrocyte sedimentation rate and C-reactive protein, and absence of treatment intensification requirement.
• Recurrence after tocilizumab discontinuation was defined as a disease flare with AOSD treatment intensification that necessitated either a ≥ 1.5-fold increase in glucocorticoid dosage and/or the initiation of a biologic agent.

TAKEAWAY:

• Over a median observation period of 5.1 years, 38 (79.2%) patients achieved remission at 6 months, of which 13 discontinued tocilizumab and the remaining 25 continued it.
• Among patients who discontinued tocilizumab on achieving remission, recurrence was noted in 50% within a year, typically after a mean period of 5.5 months after discontinuation.
• Patients in remission with longer tocilizumab intervals (> 14 days; P < .0002) or lower prednisolone doses (< 7 mg/d; P = .001) at the time of tocilizumab discontinuation showed better recurrence-free rates than those without.
• The duration of tocilizumab use, systemic feature score, and serum ferritin levels at tocilizumab discontinuation were not significantly different between patients who experienced recurrence and those who did not.

IN PRACTICE:

“Stable conditions with extended intervals of tocilizumab administration and very low doses of concomitant glucocorticoids are essential for successful discontinuation,” the authors wrote.

SOURCE:

The study was led by Hiroya Tamai, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, and published online in Rheumatology (Oxford).

LIMITATIONS:

The study was limited by its retrospective study design and a small sample size. Moreover, there could have been a selection bias as the attending physicians could use their discretion to initiate or stop tocilizumab treatment. The absence of a universally agreed-upon definition for remission or recurrence in AOSD made comparing the findings of this study with those of others challenging.

DISCLOSURES:

This study did not receive any specific funding from any bodies in public, commercial, or nonprofit sectors. Some of the authors reported receiving honoraria and research support from various pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Tocilizumab administration results in high remission rates in adult-onset Still’s disease (AOSD), but the recurrence rate increases on tocilizumab discontinuation, with a longer tocilizumab interval and lower prednisolone dose being critical for successful tocilizumab withdrawal.

METHODOLOGY:

• Tocilizumab is effective in reducing systemic inflammation and lowering glucocorticoid doses in patients with AOSD; however, the possibility of tocilizumab withdrawal has not been explored.
• This retrospective study assessed whether tocilizumab can be discontinued after achieving remission in 48 patients with AOSD.
• The systemic feature score, Pouchot score, and modified Pouchot score were used to evaluate the disease activity.
• Remission was characterized by the absence of symptoms related to Still’s disease, normal levels of erythrocyte sedimentation rate and C-reactive protein, and absence of treatment intensification requirement.
• Recurrence after tocilizumab discontinuation was defined as a disease flare with AOSD treatment intensification that necessitated either a ≥ 1.5-fold increase in glucocorticoid dosage and/or the initiation of a biologic agent.

TAKEAWAY:

• Over a median observation period of 5.1 years, 38 (79.2%) patients achieved remission at 6 months, of which 13 discontinued tocilizumab and the remaining 25 continued it.
• Among patients who discontinued tocilizumab on achieving remission, recurrence was noted in 50% within a year, typically after a mean period of 5.5 months after discontinuation.
• Patients in remission with longer tocilizumab intervals (> 14 days; P < .0002) or lower prednisolone doses (< 7 mg/d; P = .001) at the time of tocilizumab discontinuation showed better recurrence-free rates than those without.
• The duration of tocilizumab use, systemic feature score, and serum ferritin levels at tocilizumab discontinuation were not significantly different between patients who experienced recurrence and those who did not.

IN PRACTICE:

“Stable conditions with extended intervals of tocilizumab administration and very low doses of concomitant glucocorticoids are essential for successful discontinuation,” the authors wrote.

SOURCE:

The study was led by Hiroya Tamai, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, and published online in Rheumatology (Oxford).

LIMITATIONS:

The study was limited by its retrospective study design and a small sample size. Moreover, there could have been a selection bias as the attending physicians could use their discretion to initiate or stop tocilizumab treatment. The absence of a universally agreed-upon definition for remission or recurrence in AOSD made comparing the findings of this study with those of others challenging.

DISCLOSURES:

This study did not receive any specific funding from any bodies in public, commercial, or nonprofit sectors. Some of the authors reported receiving honoraria and research support from various pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Subcutaneous tocilizumab provides durable disease control rates in patients with polyarticular and systemic juvenile idiopathic arthritis (pJIA and sJIA, respectively).

METHODOLOGY:

• This long-term extension (LTE) study included 44 patients with pJIA and 38 patients with sJIA, according to the International League of Associations for Rheumatology criteria, from two 52-week phase 1b trials (NCT01904292 and NCT01904279).
• In the core trials, the dosing frequency of subcutaneous tocilizumab was determined by weight: Every 3 weeks for those < 30 kg in pJIA and every 2 weeks for those ≥ 30 kg; in sJIA, initially every 10 days for those < 30 kg, transitioning to every 2 weeks, and weekly for those ≥ 30 kg.
• Patients who had adequate disease control with subcutaneous tocilizumab, comparable with the use of intravenous tocilizumab in the core trials, continued to receive subcutaneous tocilizumab.
• The study outcome was the change in Juvenile Arthritis Disease Activity Score on 71 joints (JADAS-71, range 0-101).

TAKEAWAY:

• Disease control remained stable in both groups, with sustained improvements in median JADAS-71 scores in pJIA (−0.2 with lower frequency dosing to −0.5 with higher frequency) and sJIA (−0.1 at both dosing frequencies).
• In the pJIA group, 90% and 53% of patients weighing < 30 kg and ≥ 30 kg achieved inactive disease, respectively, whereas in the sJIA group, the respective rates were 91% and 92%.
• A total of five of 15 patients with pJIA weighing ≥ 30 kg who received subcutaneous tocilizumab every 2 weeks achieved clinical remission, whereas in other groups, the clinical remission rates ranged from 74% to 92%.
• Six patients with pJIA reported seven serious adverse events (SAEs), while five patients with sJIA experienced six SAEs. Five patients with pJIA and one patient with sJIA reported serious infections.

IN PRACTICE:

The authors concluded that subcutaneous tocilizumab treatment provided long-term disease control in patients with pJIA or sJIA, with a safety profile consistent with past studies of tocilizumab.

SOURCE:

The study was led by Hermine I. Brunner, MD, director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center. It was published online in Rheumatology (Oxford).

LIMITATIONS:

The open-label design and lack of a control group limited the analysis. Only a few patients continued the treatment for 5 years.

DISCLOSURES:

This work was supported by F. Hoffmann-La Roche Ltd. Eight authors reported receiving honoraria and consulting or speaker fees from various pharma sources. The remaining authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Subcutaneous tocilizumab provides durable disease control rates in patients with polyarticular and systemic juvenile idiopathic arthritis (pJIA and sJIA, respectively).

METHODOLOGY:

• This long-term extension (LTE) study included 44 patients with pJIA and 38 patients with sJIA, according to the International League of Associations for Rheumatology criteria, from two 52-week phase 1b trials (NCT01904292 and NCT01904279).
• In the core trials, the dosing frequency of subcutaneous tocilizumab was determined by weight: Every 3 weeks for those < 30 kg in pJIA and every 2 weeks for those ≥ 30 kg; in sJIA, initially every 10 days for those < 30 kg, transitioning to every 2 weeks, and weekly for those ≥ 30 kg.
• Patients who had adequate disease control with subcutaneous tocilizumab, comparable with the use of intravenous tocilizumab in the core trials, continued to receive subcutaneous tocilizumab.
• The study outcome was the change in Juvenile Arthritis Disease Activity Score on 71 joints (JADAS-71, range 0-101).

TAKEAWAY:

• Disease control remained stable in both groups, with sustained improvements in median JADAS-71 scores in pJIA (−0.2 with lower frequency dosing to −0.5 with higher frequency) and sJIA (−0.1 at both dosing frequencies).
• In the pJIA group, 90% and 53% of patients weighing < 30 kg and ≥ 30 kg achieved inactive disease, respectively, whereas in the sJIA group, the respective rates were 91% and 92%.
• A total of five of 15 patients with pJIA weighing ≥ 30 kg who received subcutaneous tocilizumab every 2 weeks achieved clinical remission, whereas in other groups, the clinical remission rates ranged from 74% to 92%.
• Six patients with pJIA reported seven serious adverse events (SAEs), while five patients with sJIA experienced six SAEs. Five patients with pJIA and one patient with sJIA reported serious infections.

IN PRACTICE:

The authors concluded that subcutaneous tocilizumab treatment provided long-term disease control in patients with pJIA or sJIA, with a safety profile consistent with past studies of tocilizumab.

SOURCE:

The study was led by Hermine I. Brunner, MD, director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center. It was published online in Rheumatology (Oxford).

LIMITATIONS:

The open-label design and lack of a control group limited the analysis. Only a few patients continued the treatment for 5 years.

DISCLOSURES:

This work was supported by F. Hoffmann-La Roche Ltd. Eight authors reported receiving honoraria and consulting or speaker fees from various pharma sources. The remaining authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Subcutaneous tocilizumab provides durable disease control rates in patients with polyarticular and systemic juvenile idiopathic arthritis (pJIA and sJIA, respectively).

METHODOLOGY:

• This long-term extension (LTE) study included 44 patients with pJIA and 38 patients with sJIA, according to the International League of Associations for Rheumatology criteria, from two 52-week phase 1b trials (NCT01904292 and NCT01904279).
• In the core trials, the dosing frequency of subcutaneous tocilizumab was determined by weight: Every 3 weeks for those < 30 kg in pJIA and every 2 weeks for those ≥ 30 kg; in sJIA, initially every 10 days for those < 30 kg, transitioning to every 2 weeks, and weekly for those ≥ 30 kg.
• Patients who had adequate disease control with subcutaneous tocilizumab, comparable with the use of intravenous tocilizumab in the core trials, continued to receive subcutaneous tocilizumab.
• The study outcome was the change in Juvenile Arthritis Disease Activity Score on 71 joints (JADAS-71, range 0-101).

TAKEAWAY:

• Disease control remained stable in both groups, with sustained improvements in median JADAS-71 scores in pJIA (−0.2 with lower frequency dosing to −0.5 with higher frequency) and sJIA (−0.1 at both dosing frequencies).
• In the pJIA group, 90% and 53% of patients weighing < 30 kg and ≥ 30 kg achieved inactive disease, respectively, whereas in the sJIA group, the respective rates were 91% and 92%.
• A total of five of 15 patients with pJIA weighing ≥ 30 kg who received subcutaneous tocilizumab every 2 weeks achieved clinical remission, whereas in other groups, the clinical remission rates ranged from 74% to 92%.
• Six patients with pJIA reported seven serious adverse events (SAEs), while five patients with sJIA experienced six SAEs. Five patients with pJIA and one patient with sJIA reported serious infections.

IN PRACTICE:

The authors concluded that subcutaneous tocilizumab treatment provided long-term disease control in patients with pJIA or sJIA, with a safety profile consistent with past studies of tocilizumab.

SOURCE:

The study was led by Hermine I. Brunner, MD, director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center. It was published online in Rheumatology (Oxford).

LIMITATIONS:

The open-label design and lack of a control group limited the analysis. Only a few patients continued the treatment for 5 years.

DISCLOSURES:

This work was supported by F. Hoffmann-La Roche Ltd. Eight authors reported receiving honoraria and consulting or speaker fees from various pharma sources. The remaining authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of body fat and visceral adipose tissue are associated with increased functional disability and reduced spinal mobility in patients with axial spondyloarthritis (axSpA) receiving biologic disease-modifying antirheumatic drugs (bDMARDs).

METHODOLOGY:

• Research showed that patients with axSpA respond poorly to tumor necrosis factor inhibitors if they have a high body mass index (BMI) or obesity; however, studies delving into the association between biologic therapy and body composition are limited.
• Researchers investigated the association between body composition evaluated by bioimpedance analysis and disease activity, physical function, and mobility in 74 patients with axSpA (mean age, 36.5; 71.6% men) at 6 months and 1 year after initiating bDMARDs.
• These participants from the German Spondyloarthritis Inception Cohort presented with high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs and initiated bDMARD therapy between 2015 and 2019.
• Bath Ankylosing Spondylitis Disease Activity Index and Axial Spondyloarthritis Disease Activity Score were used to measure disease activity, while Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Mobility Index assessed physical function and spinal mobility, respectively.
• BMI, fat mass, fat mass index, and visceral adipose tissue (VAT) were used to determine body composition along with other parameters.

TAKEAWAY:

• Higher BMI (parameter estimates [β], 0.081; 95% CI, 0.016-0.145), fat mass (β, 0.037; 95% CI, 0.004-0.070), and fat mass index (β, 0.125; 95% CI, 0.031-0.219) were associated with worse physical function in the overall population.
• VAT was positively associated with reduced spinal mobility (β, 0.201; 95% CI, 0.071-0.332), particularly in men.
• In women, an increase in VAT was linked to worse disease activity and functional disability.
• Treatment with bDMARDs reduced all disease activity parameters but led to an increase in BMI and fat-related parameters, indicating that lifestyle modifications are also necessary to achieve the desired outcomes with bDMARD therapy.

IN PRACTICE:

“Overall, our findings highlight the importance of maintaining a healthy body weight and body composition — characterized by adequate lean mass and reduced FM [fat mass] — to improve physical function and quality of life in patients with SpA,” the authors wrote.

SOURCE:

The study was led by Valeria Rios Rodriguez, MD, department of gastroenterology, infectiology and rheumatology, Charité Universitätsmedizin Berlin, Germany. It was published online March 20, 2024, in Rheumatology (Oxford). 

LIMITATIONS:

This study lacked a control group of patients with axSpA who did not receive biologics. It also did not include dietary habits and comorbidities such as hypertension or diabetes. Additionally, bioimpedance analysis was chosen as the method to assess body composition instead of dual-energy x-ray absorptiometry. 

DISCLOSURES:

The study was funded by the German Federal Ministry of Education and Research and the Berlin Institute of Health. Some of the authors declared receiving personal fees, grants, and consulting fees from various pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of body fat and visceral adipose tissue are associated with increased functional disability and reduced spinal mobility in patients with axial spondyloarthritis (axSpA) receiving biologic disease-modifying antirheumatic drugs (bDMARDs).

METHODOLOGY:

• Research showed that patients with axSpA respond poorly to tumor necrosis factor inhibitors if they have a high body mass index (BMI) or obesity; however, studies delving into the association between biologic therapy and body composition are limited.
• Researchers investigated the association between body composition evaluated by bioimpedance analysis and disease activity, physical function, and mobility in 74 patients with axSpA (mean age, 36.5; 71.6% men) at 6 months and 1 year after initiating bDMARDs.
• These participants from the German Spondyloarthritis Inception Cohort presented with high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs and initiated bDMARD therapy between 2015 and 2019.
• Bath Ankylosing Spondylitis Disease Activity Index and Axial Spondyloarthritis Disease Activity Score were used to measure disease activity, while Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Mobility Index assessed physical function and spinal mobility, respectively.
• BMI, fat mass, fat mass index, and visceral adipose tissue (VAT) were used to determine body composition along with other parameters.

TAKEAWAY:

• Higher BMI (parameter estimates [β], 0.081; 95% CI, 0.016-0.145), fat mass (β, 0.037; 95% CI, 0.004-0.070), and fat mass index (β, 0.125; 95% CI, 0.031-0.219) were associated with worse physical function in the overall population.
• VAT was positively associated with reduced spinal mobility (β, 0.201; 95% CI, 0.071-0.332), particularly in men.
• In women, an increase in VAT was linked to worse disease activity and functional disability.
• Treatment with bDMARDs reduced all disease activity parameters but led to an increase in BMI and fat-related parameters, indicating that lifestyle modifications are also necessary to achieve the desired outcomes with bDMARD therapy.

IN PRACTICE:

“Overall, our findings highlight the importance of maintaining a healthy body weight and body composition — characterized by adequate lean mass and reduced FM [fat mass] — to improve physical function and quality of life in patients with SpA,” the authors wrote.

SOURCE:

The study was led by Valeria Rios Rodriguez, MD, department of gastroenterology, infectiology and rheumatology, Charité Universitätsmedizin Berlin, Germany. It was published online March 20, 2024, in Rheumatology (Oxford). 

LIMITATIONS:

This study lacked a control group of patients with axSpA who did not receive biologics. It also did not include dietary habits and comorbidities such as hypertension or diabetes. Additionally, bioimpedance analysis was chosen as the method to assess body composition instead of dual-energy x-ray absorptiometry. 

DISCLOSURES:

The study was funded by the German Federal Ministry of Education and Research and the Berlin Institute of Health. Some of the authors declared receiving personal fees, grants, and consulting fees from various pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Higher levels of body fat and visceral adipose tissue are associated with increased functional disability and reduced spinal mobility in patients with axial spondyloarthritis (axSpA) receiving biologic disease-modifying antirheumatic drugs (bDMARDs).

METHODOLOGY:

• Research showed that patients with axSpA respond poorly to tumor necrosis factor inhibitors if they have a high body mass index (BMI) or obesity; however, studies delving into the association between biologic therapy and body composition are limited.
• Researchers investigated the association between body composition evaluated by bioimpedance analysis and disease activity, physical function, and mobility in 74 patients with axSpA (mean age, 36.5; 71.6% men) at 6 months and 1 year after initiating bDMARDs.
• These participants from the German Spondyloarthritis Inception Cohort presented with high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs and initiated bDMARD therapy between 2015 and 2019.
• Bath Ankylosing Spondylitis Disease Activity Index and Axial Spondyloarthritis Disease Activity Score were used to measure disease activity, while Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Mobility Index assessed physical function and spinal mobility, respectively.
• BMI, fat mass, fat mass index, and visceral adipose tissue (VAT) were used to determine body composition along with other parameters.

TAKEAWAY:

• Higher BMI (parameter estimates [β], 0.081; 95% CI, 0.016-0.145), fat mass (β, 0.037; 95% CI, 0.004-0.070), and fat mass index (β, 0.125; 95% CI, 0.031-0.219) were associated with worse physical function in the overall population.
• VAT was positively associated with reduced spinal mobility (β, 0.201; 95% CI, 0.071-0.332), particularly in men.
• In women, an increase in VAT was linked to worse disease activity and functional disability.
• Treatment with bDMARDs reduced all disease activity parameters but led to an increase in BMI and fat-related parameters, indicating that lifestyle modifications are also necessary to achieve the desired outcomes with bDMARD therapy.

IN PRACTICE:

“Overall, our findings highlight the importance of maintaining a healthy body weight and body composition — characterized by adequate lean mass and reduced FM [fat mass] — to improve physical function and quality of life in patients with SpA,” the authors wrote.

SOURCE:

The study was led by Valeria Rios Rodriguez, MD, department of gastroenterology, infectiology and rheumatology, Charité Universitätsmedizin Berlin, Germany. It was published online March 20, 2024, in Rheumatology (Oxford). 

LIMITATIONS:

This study lacked a control group of patients with axSpA who did not receive biologics. It also did not include dietary habits and comorbidities such as hypertension or diabetes. Additionally, bioimpedance analysis was chosen as the method to assess body composition instead of dual-energy x-ray absorptiometry. 

DISCLOSURES:

The study was funded by the German Federal Ministry of Education and Research and the Berlin Institute of Health. Some of the authors declared receiving personal fees, grants, and consulting fees from various pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

According to this meta-analysis, psoriatic arthritis (PsA) affects 112 out of every 100,000 adults globally, with higher rates observed in Europe and North America than in Asia and South America, according to an analysis of 30 studies.

METHODOLOGY:

• Many previous epidemiological studies have estimated the global prevalence of PsA but have reported marked variations, which could be explained by differences in methodology and inclusion criteria.
• This meta-analysis used data from 30 studies conducted between 1982 and 2020 to estimate the worldwide prevalence of PsA in the general adult population, giving particular attention to methodological differences among the included studies.
• The included studies were either population-based (n = 13) or based on health administrative records (n = 17) and covered over 180 million adults across 24 countries.
• Overall, 15 studies were from Europe, seven from Asia, six from North America, and two from South America.

TAKEAWAY:

• The global prevalence of PsA was estimated at 113 (95% CI, 64-198) and 109 (75-158) cases per 100,000 based on population-based studies and health administrative data studies, respectively.
• The pooled global prevalence of PsA (combining the population-based and health administrative studies) was 112 cases per 100,000 (95% CI, 83-151).
• Combining both study designs, the global prevalence rates of PsA were 188 (95% CI, 128-289) cases per 100,000 for Europe, 48 (95% CI, 20-115) for Asia, 133 (95% CI, 93-191) for North America, and 17 (95% CI, 4-70) for South America.

IN PRACTICE:

“Robust estimates of prevalence are crucial for healthcare planning and resource allocation,” wrote the authors.

SOURCE:

The study was conducted by Stephanie Lembke, MSc, and colleagues from the Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Scotland. It was published online in Rheumatology (Oxford).

LIMITATIONS:

The meta-analysis had high levels of uncertainty and high heterogeneity between studies. In countries with unequal healthcare access, using data from statutory or private insurance databases to calculate PsA prevalence may systematically exclude uninsured individuals or those covered by private insurers. Moreover, the data were insufficient for a statistically meaningful subgroup analysis.

DISCLOSURES:

The study did not receive any specific funding from any public, commercial, or nonprofit sectors to carry out this work. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

According to this meta-analysis, psoriatic arthritis (PsA) affects 112 out of every 100,000 adults globally, with higher rates observed in Europe and North America than in Asia and South America, according to an analysis of 30 studies.

METHODOLOGY:

• Many previous epidemiological studies have estimated the global prevalence of PsA but have reported marked variations, which could be explained by differences in methodology and inclusion criteria.
• This meta-analysis used data from 30 studies conducted between 1982 and 2020 to estimate the worldwide prevalence of PsA in the general adult population, giving particular attention to methodological differences among the included studies.
• The included studies were either population-based (n = 13) or based on health administrative records (n = 17) and covered over 180 million adults across 24 countries.
• Overall, 15 studies were from Europe, seven from Asia, six from North America, and two from South America.

TAKEAWAY:

• The global prevalence of PsA was estimated at 113 (95% CI, 64-198) and 109 (75-158) cases per 100,000 based on population-based studies and health administrative data studies, respectively.
• The pooled global prevalence of PsA (combining the population-based and health administrative studies) was 112 cases per 100,000 (95% CI, 83-151).
• Combining both study designs, the global prevalence rates of PsA were 188 (95% CI, 128-289) cases per 100,000 for Europe, 48 (95% CI, 20-115) for Asia, 133 (95% CI, 93-191) for North America, and 17 (95% CI, 4-70) for South America.

IN PRACTICE:

“Robust estimates of prevalence are crucial for healthcare planning and resource allocation,” wrote the authors.

SOURCE:

The study was conducted by Stephanie Lembke, MSc, and colleagues from the Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Scotland. It was published online in Rheumatology (Oxford).

LIMITATIONS:

The meta-analysis had high levels of uncertainty and high heterogeneity between studies. In countries with unequal healthcare access, using data from statutory or private insurance databases to calculate PsA prevalence may systematically exclude uninsured individuals or those covered by private insurers. Moreover, the data were insufficient for a statistically meaningful subgroup analysis.

DISCLOSURES:

The study did not receive any specific funding from any public, commercial, or nonprofit sectors to carry out this work. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

According to this meta-analysis, psoriatic arthritis (PsA) affects 112 out of every 100,000 adults globally, with higher rates observed in Europe and North America than in Asia and South America, according to an analysis of 30 studies.

METHODOLOGY:

• Many previous epidemiological studies have estimated the global prevalence of PsA but have reported marked variations, which could be explained by differences in methodology and inclusion criteria.
• This meta-analysis used data from 30 studies conducted between 1982 and 2020 to estimate the worldwide prevalence of PsA in the general adult population, giving particular attention to methodological differences among the included studies.
• The included studies were either population-based (n = 13) or based on health administrative records (n = 17) and covered over 180 million adults across 24 countries.
• Overall, 15 studies were from Europe, seven from Asia, six from North America, and two from South America.

TAKEAWAY:

• The global prevalence of PsA was estimated at 113 (95% CI, 64-198) and 109 (75-158) cases per 100,000 based on population-based studies and health administrative data studies, respectively.
• The pooled global prevalence of PsA (combining the population-based and health administrative studies) was 112 cases per 100,000 (95% CI, 83-151).
• Combining both study designs, the global prevalence rates of PsA were 188 (95% CI, 128-289) cases per 100,000 for Europe, 48 (95% CI, 20-115) for Asia, 133 (95% CI, 93-191) for North America, and 17 (95% CI, 4-70) for South America.

IN PRACTICE:

“Robust estimates of prevalence are crucial for healthcare planning and resource allocation,” wrote the authors.

SOURCE:

The study was conducted by Stephanie Lembke, MSc, and colleagues from the Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Scotland. It was published online in Rheumatology (Oxford).

LIMITATIONS:

The meta-analysis had high levels of uncertainty and high heterogeneity between studies. In countries with unequal healthcare access, using data from statutory or private insurance databases to calculate PsA prevalence may systematically exclude uninsured individuals or those covered by private insurers. Moreover, the data were insufficient for a statistically meaningful subgroup analysis.

DISCLOSURES:

The study did not receive any specific funding from any public, commercial, or nonprofit sectors to carry out this work. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
 

Stopping Steroids After Remission in GPA

In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.

However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).

A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.

The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
 

Abatacept Falls Short for Preventing Relapse in GPA

Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.

In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.

The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.

A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.

The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.

The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
 

Plasma Exchange Improves Kidney Function in AAV

Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.

The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m² at weeks 12, 26, and 52.

The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m², compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.

The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
 

Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV

A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.

Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.

The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.

No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.

The study was supported by the French Ministry of Health.

Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
 

Stopping Steroids After Remission in GPA

In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.

However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).

A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.

The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
 

Abatacept Falls Short for Preventing Relapse in GPA

Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.

In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.

The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.

A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.

The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.

The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
 

Plasma Exchange Improves Kidney Function in AAV

Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.

The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m² at weeks 12, 26, and 52.

The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m², compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.

The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
 

Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV

A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.

Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.

The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.

No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.

The study was supported by the French Ministry of Health.

Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
 

Stopping Steroids After Remission in GPA

In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.

However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).

A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.

The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
 

Abatacept Falls Short for Preventing Relapse in GPA

Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.

In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.

The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.

A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.

The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.

The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
 

Plasma Exchange Improves Kidney Function in AAV

Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.

The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m² at weeks 12, 26, and 52.

The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m², compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.

The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
 

Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV

A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.

Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.

The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.

No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.

The study was supported by the French Ministry of Health.

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Bond University

University of Georgia

University of Sydney

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Bond University

University of Georgia

University of Sydney

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Bond University

University of Georgia

University of Sydney