Rheumatology

TOPLINE:

Anti-acid drugs used by patients with systemic sclerosis reduce the bioavailability of mycophenolate mofetil (MMF).

METHODOLOGY:

• Researchers conducted an open-label, pragmatic crossover study of 20 patients (all female) with systemic sclerosis at a single center who were on a stable MMF dose (1.5-2 g/day) for the last 3 months or more.
• Participants sequentially took MMF alone for 1 month, then with the H2 receptor blocker (HRB) ranitidine 300 mg/day in the second month, then with the proton pump inhibitor (PPI) esomeprazole 40 mg/day in the third month.
• Researchers measured the bioavailability of MMF in the patients during treatment with ranitidine or esomeprazole and the impact of the drugs on the total GI score of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 instrument.
• Patients were excluded if they were receiving co-prescription of cholestyramine, magnesium- or aluminum-containing antacids, and rifampicin; taking prednisolone-equivalent dose > 5 mg/day; taking MMF plus a PPI or an HRB at baseline; living with chronic kidney disease with a glomerular filtration rate < 30 mL/min; positive for HIV, HCV, or HBV; or living with end-stage lung disease or gastroduodenal ulcers.

TAKEAWAY:

• Mean estimated 12-hour area under curve levels of mycophenolic acid dropped by 32.7% (mean difference = 22.28 mcg h mL–1) when patients added esomeprazole, and they dipped by 21.97% (mean difference = 14.93 mcg h mL–1) when they added ranitidine vs. MMF alone.
• The pharmacokinetic parameter T-max did not differ significantly between MMF alone vs. MMF plus ranitidine but was significantly different with esomeprazole. C-max significantly declined with administration of ranitidine or esomeprazole vs. MMF alone.
• Total GI scores dipped when patients added esomeprazole or ranitidine.

IN PRACTICE:

In patients with significant gastroesophageal reflux disease symptoms who need to take MMF, management options may include monitoring MMF drug levels, switching to enteric-coated mycophenolate sodium, and spacing doses with anti-acid drugs.

SOURCE:

Glaxon Alex, MD, and colleagues from the Center for Arthritis and Rheumatism Excellence in Kochi, India, conducted the study, which was published online in Seminars in Arthritis & Rheumatism.

LIMITATIONS:

The sample size is small, and the optimum dose of MMF is unknown.

DISCLOSURES:

The study had no outside funding. The authors report no relevant financial relationships.

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

TOPLINE:

Anti-acid drugs used by patients with systemic sclerosis reduce the bioavailability of mycophenolate mofetil (MMF).

METHODOLOGY:

• Researchers conducted an open-label, pragmatic crossover study of 20 patients (all female) with systemic sclerosis at a single center who were on a stable MMF dose (1.5-2 g/day) for the last 3 months or more.
• Participants sequentially took MMF alone for 1 month, then with the H2 receptor blocker (HRB) ranitidine 300 mg/day in the second month, then with the proton pump inhibitor (PPI) esomeprazole 40 mg/day in the third month.
• Researchers measured the bioavailability of MMF in the patients during treatment with ranitidine or esomeprazole and the impact of the drugs on the total GI score of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 instrument.
• Patients were excluded if they were receiving co-prescription of cholestyramine, magnesium- or aluminum-containing antacids, and rifampicin; taking prednisolone-equivalent dose > 5 mg/day; taking MMF plus a PPI or an HRB at baseline; living with chronic kidney disease with a glomerular filtration rate < 30 mL/min; positive for HIV, HCV, or HBV; or living with end-stage lung disease or gastroduodenal ulcers.

TAKEAWAY:

• Mean estimated 12-hour area under curve levels of mycophenolic acid dropped by 32.7% (mean difference = 22.28 mcg h mL–1) when patients added esomeprazole, and they dipped by 21.97% (mean difference = 14.93 mcg h mL–1) when they added ranitidine vs. MMF alone.
• The pharmacokinetic parameter T-max did not differ significantly between MMF alone vs. MMF plus ranitidine but was significantly different with esomeprazole. C-max significantly declined with administration of ranitidine or esomeprazole vs. MMF alone.
• Total GI scores dipped when patients added esomeprazole or ranitidine.

IN PRACTICE:

In patients with significant gastroesophageal reflux disease symptoms who need to take MMF, management options may include monitoring MMF drug levels, switching to enteric-coated mycophenolate sodium, and spacing doses with anti-acid drugs.

SOURCE:

Glaxon Alex, MD, and colleagues from the Center for Arthritis and Rheumatism Excellence in Kochi, India, conducted the study, which was published online in Seminars in Arthritis & Rheumatism.

LIMITATIONS:

The sample size is small, and the optimum dose of MMF is unknown.

DISCLOSURES:

The study had no outside funding. The authors report no relevant financial relationships.

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

TOPLINE:

Anti-acid drugs used by patients with systemic sclerosis reduce the bioavailability of mycophenolate mofetil (MMF).

METHODOLOGY:

• Researchers conducted an open-label, pragmatic crossover study of 20 patients (all female) with systemic sclerosis at a single center who were on a stable MMF dose (1.5-2 g/day) for the last 3 months or more.
• Participants sequentially took MMF alone for 1 month, then with the H2 receptor blocker (HRB) ranitidine 300 mg/day in the second month, then with the proton pump inhibitor (PPI) esomeprazole 40 mg/day in the third month.
• Researchers measured the bioavailability of MMF in the patients during treatment with ranitidine or esomeprazole and the impact of the drugs on the total GI score of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 instrument.
• Patients were excluded if they were receiving co-prescription of cholestyramine, magnesium- or aluminum-containing antacids, and rifampicin; taking prednisolone-equivalent dose > 5 mg/day; taking MMF plus a PPI or an HRB at baseline; living with chronic kidney disease with a glomerular filtration rate < 30 mL/min; positive for HIV, HCV, or HBV; or living with end-stage lung disease or gastroduodenal ulcers.

TAKEAWAY:

• Mean estimated 12-hour area under curve levels of mycophenolic acid dropped by 32.7% (mean difference = 22.28 mcg h mL–1) when patients added esomeprazole, and they dipped by 21.97% (mean difference = 14.93 mcg h mL–1) when they added ranitidine vs. MMF alone.
• The pharmacokinetic parameter T-max did not differ significantly between MMF alone vs. MMF plus ranitidine but was significantly different with esomeprazole. C-max significantly declined with administration of ranitidine or esomeprazole vs. MMF alone.
• Total GI scores dipped when patients added esomeprazole or ranitidine.

IN PRACTICE:

In patients with significant gastroesophageal reflux disease symptoms who need to take MMF, management options may include monitoring MMF drug levels, switching to enteric-coated mycophenolate sodium, and spacing doses with anti-acid drugs.

SOURCE:

Glaxon Alex, MD, and colleagues from the Center for Arthritis and Rheumatism Excellence in Kochi, India, conducted the study, which was published online in Seminars in Arthritis & Rheumatism.

LIMITATIONS:

The sample size is small, and the optimum dose of MMF is unknown.

DISCLOSURES:

The study had no outside funding. The authors report no relevant financial relationships.

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

LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.

In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.

Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.

Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
 

Gender-sensitive approach

Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:

• Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
• Sex-specific differences in communication between male and female patients and between male and female physicians.

Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”

In contrast, women with axSpA exhibit the following differences:

• It is more likely for the cervical spine to be affected.
• Women are more likely to suffer from peripheral joint involvement.
• They suffer more from whole body pain.
• They have fatigue and exhaustion.  
• They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
• They are rarely HLA-B27 positive.

“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.

A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.

However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).

For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
 

TNF blockers

Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”

Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.

The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.

She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:

• Genetic, physical, or hormonal causes
• Widespread pain or fibromyalgia
• Late diagnosis or late application of therapy, which lowers the chances of remission.

Even the science itself has shown the following sex-specific shortcomings:

• Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
• Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
• Most of the data come from epidemiological analyses (not from basic research)
• Gaps in medical textbooks

Communication differences

Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:

• Describe their symptoms in terms of specifics
• Do not like to admit having mental health issues
• Are three to five times more likely to commit suicide because of depression than women

On the other hand, female patients behave in the following ways:

• Look for an explanation for their symptoms
• Often do not have their physical symptoms taken seriously
• Are often pushed in a psychosomatic direction.

Female physicians focus on the following questions:

• Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
• Psychosocial situations: consultations last 1 minute longer (10%).

Male physicians focus on the following questions:

• Medical history
• Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
• Diagnostics

Recognition and training

A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:

• 15% higher risk for a worse surgery result
• 16% higher risk for complications
• 11% higher risk for repeat hospitalization
• 20% higher risk for a longer period of hospitalization
• 32% higher risk for mortality

The study authors provided the following potential reasons for these differences:

• Male physicians underestimate the severity of symptoms in their female patients
• Women are less comfortable indicating their postoperative pain to a male physician
• Different working style and treatment decisions between female and male physicians
• Unconsciously incorporated role patterns and preconceptions

“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.

In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.

Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.

Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
 

Gender-sensitive approach

Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:

• Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
• Sex-specific differences in communication between male and female patients and between male and female physicians.

Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”

In contrast, women with axSpA exhibit the following differences:

• It is more likely for the cervical spine to be affected.
• Women are more likely to suffer from peripheral joint involvement.
• They suffer more from whole body pain.
• They have fatigue and exhaustion.  
• They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
• They are rarely HLA-B27 positive.

“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.

A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.

However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).

For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
 

TNF blockers

Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”

Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.

The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.

She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:

• Genetic, physical, or hormonal causes
• Widespread pain or fibromyalgia
• Late diagnosis or late application of therapy, which lowers the chances of remission.

Even the science itself has shown the following sex-specific shortcomings:

• Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
• Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
• Most of the data come from epidemiological analyses (not from basic research)
• Gaps in medical textbooks

Communication differences

Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:

• Describe their symptoms in terms of specifics
• Do not like to admit having mental health issues
• Are three to five times more likely to commit suicide because of depression than women

On the other hand, female patients behave in the following ways:

• Look for an explanation for their symptoms
• Often do not have their physical symptoms taken seriously
• Are often pushed in a psychosomatic direction.

Female physicians focus on the following questions:

• Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
• Psychosocial situations: consultations last 1 minute longer (10%).

Male physicians focus on the following questions:

• Medical history
• Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
• Diagnostics

Recognition and training

A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:

• 15% higher risk for a worse surgery result
• 16% higher risk for complications
• 11% higher risk for repeat hospitalization
• 20% higher risk for a longer period of hospitalization
• 32% higher risk for mortality

The study authors provided the following potential reasons for these differences:

• Male physicians underestimate the severity of symptoms in their female patients
• Women are less comfortable indicating their postoperative pain to a male physician
• Different working style and treatment decisions between female and male physicians
• Unconsciously incorporated role patterns and preconceptions

“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.

In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.

Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.

Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
 

Gender-sensitive approach

Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:

• Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
• Sex-specific differences in communication between male and female patients and between male and female physicians.

Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”

In contrast, women with axSpA exhibit the following differences:

• It is more likely for the cervical spine to be affected.
• Women are more likely to suffer from peripheral joint involvement.
• They suffer more from whole body pain.
• They have fatigue and exhaustion.  
• They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
• They are rarely HLA-B27 positive.

“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.

A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.

However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).

For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
 

TNF blockers

Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”

Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.

The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.

She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:

• Genetic, physical, or hormonal causes
• Widespread pain or fibromyalgia
• Late diagnosis or late application of therapy, which lowers the chances of remission.

Even the science itself has shown the following sex-specific shortcomings:

• Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
• Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
• Most of the data come from epidemiological analyses (not from basic research)
• Gaps in medical textbooks

Communication differences

Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:

• Describe their symptoms in terms of specifics
• Do not like to admit having mental health issues
• Are three to five times more likely to commit suicide because of depression than women

On the other hand, female patients behave in the following ways:

• Look for an explanation for their symptoms
• Often do not have their physical symptoms taken seriously
• Are often pushed in a psychosomatic direction.

Female physicians focus on the following questions:

• Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
• Psychosocial situations: consultations last 1 minute longer (10%).

Male physicians focus on the following questions:

• Medical history
• Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
• Diagnostics

Recognition and training

A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:

• 15% higher risk for a worse surgery result
• 16% higher risk for complications
• 11% higher risk for repeat hospitalization
• 20% higher risk for a longer period of hospitalization
• 32% higher risk for mortality

The study authors provided the following potential reasons for these differences:

• Male physicians underestimate the severity of symptoms in their female patients
• Women are less comfortable indicating their postoperative pain to a male physician
• Different working style and treatment decisions between female and male physicians
• Unconsciously incorporated role patterns and preconceptions

“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

The Food and Drug Administration has approved an intravenous (IV) formulation of secukinumab (Cosentyx) for the treatment of adults with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis (nr-axSpA).

Secukinumab is the only treatment approved in an IV formulation that specifically targets and blocks interleukin-17A and the only non–tumor necrosis factor alpha IV option available to treat the three indications of PsA, AS, and nr-axSpA, according to a press release from the drug’s manufacturer, Novartis.

The approval marks the first new IV treatment in 6 years for these three conditions. The drug was first approved in 2015 and up to now has been available only as a subcutaneous injection.

The new formulation is also approved for secukinumab’s other indications of plaque psoriasis in people aged 6 years or older, children aged 2 years or older with PsA, and enthesitis-related arthritis in patients aged 4 years or older.

“A significant portion of the millions of PsA, AS, and nr-axSpA patients in the United States require treatment through IV infusions for a variety of reasons, including not being comfortable with self-injections or simply preferring to have treatments administered in their health care provider’s office,” Philip J. Mease, MD, clinical professor at the University of Washington, Seattle, and director of rheumatology research at the Swedish Medical Center, Seattle, said in the press release. “The approval of Cosentyx as an IV formulation is an important milestone for patients because it expands the treatment options available to them with a different mechanism of action than existing biologic IV therapies, along with the comfort and familiarity of an established treatment.”

This IV formulation is administered monthly in a 30-minute, weight-based dosing regimen. This new option will become available before the end of the year, Novartis said.

“With this approval of Cosentyx as an IV formulation, along with the subcutaneous formulation, we can broaden the use of Cosentyx to help more patients manage their condition with a medicine backed by more than a decade of clinical research and 8 years of real-world experience,” said Christy Siegel, vice president and head of immunology, Novartis U.S.

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

The Food and Drug Administration has approved an intravenous (IV) formulation of secukinumab (Cosentyx) for the treatment of adults with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis (nr-axSpA).

Secukinumab is the only treatment approved in an IV formulation that specifically targets and blocks interleukin-17A and the only non–tumor necrosis factor alpha IV option available to treat the three indications of PsA, AS, and nr-axSpA, according to a press release from the drug’s manufacturer, Novartis.

The approval marks the first new IV treatment in 6 years for these three conditions. The drug was first approved in 2015 and up to now has been available only as a subcutaneous injection.

The new formulation is also approved for secukinumab’s other indications of plaque psoriasis in people aged 6 years or older, children aged 2 years or older with PsA, and enthesitis-related arthritis in patients aged 4 years or older.

“A significant portion of the millions of PsA, AS, and nr-axSpA patients in the United States require treatment through IV infusions for a variety of reasons, including not being comfortable with self-injections or simply preferring to have treatments administered in their health care provider’s office,” Philip J. Mease, MD, clinical professor at the University of Washington, Seattle, and director of rheumatology research at the Swedish Medical Center, Seattle, said in the press release. “The approval of Cosentyx as an IV formulation is an important milestone for patients because it expands the treatment options available to them with a different mechanism of action than existing biologic IV therapies, along with the comfort and familiarity of an established treatment.”

This IV formulation is administered monthly in a 30-minute, weight-based dosing regimen. This new option will become available before the end of the year, Novartis said.

“With this approval of Cosentyx as an IV formulation, along with the subcutaneous formulation, we can broaden the use of Cosentyx to help more patients manage their condition with a medicine backed by more than a decade of clinical research and 8 years of real-world experience,” said Christy Siegel, vice president and head of immunology, Novartis U.S.

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

The Food and Drug Administration has approved an intravenous (IV) formulation of secukinumab (Cosentyx) for the treatment of adults with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis (nr-axSpA).

Secukinumab is the only treatment approved in an IV formulation that specifically targets and blocks interleukin-17A and the only non–tumor necrosis factor alpha IV option available to treat the three indications of PsA, AS, and nr-axSpA, according to a press release from the drug’s manufacturer, Novartis.

The approval marks the first new IV treatment in 6 years for these three conditions. The drug was first approved in 2015 and up to now has been available only as a subcutaneous injection.

The new formulation is also approved for secukinumab’s other indications of plaque psoriasis in people aged 6 years or older, children aged 2 years or older with PsA, and enthesitis-related arthritis in patients aged 4 years or older.

“A significant portion of the millions of PsA, AS, and nr-axSpA patients in the United States require treatment through IV infusions for a variety of reasons, including not being comfortable with self-injections or simply preferring to have treatments administered in their health care provider’s office,” Philip J. Mease, MD, clinical professor at the University of Washington, Seattle, and director of rheumatology research at the Swedish Medical Center, Seattle, said in the press release. “The approval of Cosentyx as an IV formulation is an important milestone for patients because it expands the treatment options available to them with a different mechanism of action than existing biologic IV therapies, along with the comfort and familiarity of an established treatment.”

This IV formulation is administered monthly in a 30-minute, weight-based dosing regimen. This new option will become available before the end of the year, Novartis said.

“With this approval of Cosentyx as an IV formulation, along with the subcutaneous formulation, we can broaden the use of Cosentyx to help more patients manage their condition with a medicine backed by more than a decade of clinical research and 8 years of real-world experience,” said Christy Siegel, vice president and head of immunology, Novartis U.S.

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

TOPLINE:

Matched cohort studies revealed infrequent adverse events (AEs) with either treatment, but the number needed to harm for any AE was more than three times higher with colchicine versus NSAIDs.

METHODOLOGY:

• The researchers conducted two matched retrospective cohort studies using the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics primary care datasets to compare AEs in adults initiating allopurinol for gout with and without colchicine or NSAID prophylaxis.
• For the study, 13,945 patients with gout who received colchicine were matched to 13,945 patients who received no prophylaxis. In addition, 25,980 patients with gout who received NSAIDs were matched to 25,980 who received no prophylaxis.
• The researchers used proportional hazard models to explore the associations between prophylaxis with either colchicine or NSAIDs and AEs.

TAKEAWAY:

• The incidence of most AEs was less than 200 per 10,000 patient-years, but the most common AE among patients given colchicine was diarrhea, with an incidence of 784.4 per 10,000 person-years, whereas the most common AE in those given NSAIDs was angina, with an incidence of 466.6 per 10,000 person-years.
• The number needed to harm in relation to any AE was 14.7 for colchicine, driven mainly by diarrhea, and 48.1 for NSAID.
• Compared with patients who started allopurinol without prophylaxis, those treated with colchicine were more likely to experience diarrhea, myocardial infarction, neuropathy, myalgia, and bone marrow suppression, whereas those treated with NSAIDs were more likely to experience angina, acute kidney injury, myocardial infarction, and peptic ulcer disease.
• Diarrhea, the most common AE, occurred in 17.9% of individuals who received colchicine.

IN PRACTICE:

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions and the choice between colchicine or NSAID for prophylaxis when initiating allopurinol, directly benefiting people with gout and their clinicians,” the authors write.

SOURCE:

First author Edward Roddy, MD, of Keele (England) University, and colleagues published their report online in BMJ’s Annals of the Rheumatic Diseases.

LIMITATIONS:

The study identified gout based on clinical diagnosis in primary care and only considered AEs serious enough to merit consultation or hospitalization; other limitations included the observational design and lack of data on the use of over-the-counter NSAIDs.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research’s Research for Patient Benefit program. The researchers had no financial conflicts to disclose.

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

TOPLINE:

Matched cohort studies revealed infrequent adverse events (AEs) with either treatment, but the number needed to harm for any AE was more than three times higher with colchicine versus NSAIDs.

METHODOLOGY:

• The researchers conducted two matched retrospective cohort studies using the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics primary care datasets to compare AEs in adults initiating allopurinol for gout with and without colchicine or NSAID prophylaxis.
• For the study, 13,945 patients with gout who received colchicine were matched to 13,945 patients who received no prophylaxis. In addition, 25,980 patients with gout who received NSAIDs were matched to 25,980 who received no prophylaxis.
• The researchers used proportional hazard models to explore the associations between prophylaxis with either colchicine or NSAIDs and AEs.

TAKEAWAY:

• The incidence of most AEs was less than 200 per 10,000 patient-years, but the most common AE among patients given colchicine was diarrhea, with an incidence of 784.4 per 10,000 person-years, whereas the most common AE in those given NSAIDs was angina, with an incidence of 466.6 per 10,000 person-years.
• The number needed to harm in relation to any AE was 14.7 for colchicine, driven mainly by diarrhea, and 48.1 for NSAID.
• Compared with patients who started allopurinol without prophylaxis, those treated with colchicine were more likely to experience diarrhea, myocardial infarction, neuropathy, myalgia, and bone marrow suppression, whereas those treated with NSAIDs were more likely to experience angina, acute kidney injury, myocardial infarction, and peptic ulcer disease.
• Diarrhea, the most common AE, occurred in 17.9% of individuals who received colchicine.

IN PRACTICE:

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions and the choice between colchicine or NSAID for prophylaxis when initiating allopurinol, directly benefiting people with gout and their clinicians,” the authors write.

SOURCE:

First author Edward Roddy, MD, of Keele (England) University, and colleagues published their report online in BMJ’s Annals of the Rheumatic Diseases.

LIMITATIONS:

The study identified gout based on clinical diagnosis in primary care and only considered AEs serious enough to merit consultation or hospitalization; other limitations included the observational design and lack of data on the use of over-the-counter NSAIDs.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research’s Research for Patient Benefit program. The researchers had no financial conflicts to disclose.

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

TOPLINE:

Matched cohort studies revealed infrequent adverse events (AEs) with either treatment, but the number needed to harm for any AE was more than three times higher with colchicine versus NSAIDs.

METHODOLOGY:

• The researchers conducted two matched retrospective cohort studies using the U.K. Clinical Practice Research Datalink and the Hospital Episode Statistics primary care datasets to compare AEs in adults initiating allopurinol for gout with and without colchicine or NSAID prophylaxis.
• For the study, 13,945 patients with gout who received colchicine were matched to 13,945 patients who received no prophylaxis. In addition, 25,980 patients with gout who received NSAIDs were matched to 25,980 who received no prophylaxis.
• The researchers used proportional hazard models to explore the associations between prophylaxis with either colchicine or NSAIDs and AEs.

TAKEAWAY:

• The incidence of most AEs was less than 200 per 10,000 patient-years, but the most common AE among patients given colchicine was diarrhea, with an incidence of 784.4 per 10,000 person-years, whereas the most common AE in those given NSAIDs was angina, with an incidence of 466.6 per 10,000 person-years.
• The number needed to harm in relation to any AE was 14.7 for colchicine, driven mainly by diarrhea, and 48.1 for NSAID.
• Compared with patients who started allopurinol without prophylaxis, those treated with colchicine were more likely to experience diarrhea, myocardial infarction, neuropathy, myalgia, and bone marrow suppression, whereas those treated with NSAIDs were more likely to experience angina, acute kidney injury, myocardial infarction, and peptic ulcer disease.
• Diarrhea, the most common AE, occurred in 17.9% of individuals who received colchicine.

IN PRACTICE:

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions and the choice between colchicine or NSAID for prophylaxis when initiating allopurinol, directly benefiting people with gout and their clinicians,” the authors write.

SOURCE:

First author Edward Roddy, MD, of Keele (England) University, and colleagues published their report online in BMJ’s Annals of the Rheumatic Diseases.

LIMITATIONS:

The study identified gout based on clinical diagnosis in primary care and only considered AEs serious enough to merit consultation or hospitalization; other limitations included the observational design and lack of data on the use of over-the-counter NSAIDs.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research’s Research for Patient Benefit program. The researchers had no financial conflicts to disclose.

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

TOPLINE:

Research from South Korea provides additional evidence for the connection between COVID-19 and an increased risk for autoimmune conditions post infection.

METHODOLOGY:

• In this retrospective study, researchers identified 354,527 individuals diagnosed with COVID-19 via polymerase chain reaction (PCR) testing from Oct. 8, 2020, to Dec. 31, 2021.
• Researchers compared the COVID-19 group with 6,134,940 healthy individuals who had no evidence of COVID-19 to quantify the risk for autoimmune and autoinflammatory connective tissue disorders.
• Patients were followed until diagnosis, death, or end of study period (Dec. 31, 2021).

TAKEAWAY:

• Risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody–associated vasculitis, Crohn’s disease, and sarcoidosis were higher in the COVID-19 group.
• Patients with more severe COVID-19 (admitted to the ICU) were at greater risk for many autoimmune conditions, including alopecia totalis, psoriasis, vitiligo, and vasculitis.
•  

IN PRACTICE:

“Our results emphasize the need to focus on managing not only the acute stages of COVID-19 itself but also autoimmune diseases as complications of COVID-19,” the authors wrote.

SOURCE:

Sung Ha Lim, MD, of Yonsei University, Wonju, South Korea, was the first author of the study, published in JAMA Network Open.

LIMITATIONS:

The study was retrospective and was composed almost exclusively of individuals from a single ethnicity. The study could have included individuals with COVID-19 in the control group who did not undergo PCR testing. The analysis did not include detailed information on each patient, including genetic information, that could have contributed to autoimmune disease risk.

DISCLOSURES:

The study was supported by a fund from the research program of the Korea Medical Institute and by grants from the Korea Health Industry Development Institute, the Korean Ministry of Health & Welfare, and the National Research Foundation of Korea. The authors disclosed no relevant financial relationships.

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

TOPLINE:

Research from South Korea provides additional evidence for the connection between COVID-19 and an increased risk for autoimmune conditions post infection.

METHODOLOGY:

• In this retrospective study, researchers identified 354,527 individuals diagnosed with COVID-19 via polymerase chain reaction (PCR) testing from Oct. 8, 2020, to Dec. 31, 2021.
• Researchers compared the COVID-19 group with 6,134,940 healthy individuals who had no evidence of COVID-19 to quantify the risk for autoimmune and autoinflammatory connective tissue disorders.
• Patients were followed until diagnosis, death, or end of study period (Dec. 31, 2021).

TAKEAWAY:

• Risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody–associated vasculitis, Crohn’s disease, and sarcoidosis were higher in the COVID-19 group.
• Patients with more severe COVID-19 (admitted to the ICU) were at greater risk for many autoimmune conditions, including alopecia totalis, psoriasis, vitiligo, and vasculitis.
•  

IN PRACTICE:

“Our results emphasize the need to focus on managing not only the acute stages of COVID-19 itself but also autoimmune diseases as complications of COVID-19,” the authors wrote.

SOURCE:

Sung Ha Lim, MD, of Yonsei University, Wonju, South Korea, was the first author of the study, published in JAMA Network Open.

LIMITATIONS:

The study was retrospective and was composed almost exclusively of individuals from a single ethnicity. The study could have included individuals with COVID-19 in the control group who did not undergo PCR testing. The analysis did not include detailed information on each patient, including genetic information, that could have contributed to autoimmune disease risk.

DISCLOSURES:

The study was supported by a fund from the research program of the Korea Medical Institute and by grants from the Korea Health Industry Development Institute, the Korean Ministry of Health & Welfare, and the National Research Foundation of Korea. The authors disclosed no relevant financial relationships.

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

TOPLINE:

Research from South Korea provides additional evidence for the connection between COVID-19 and an increased risk for autoimmune conditions post infection.

METHODOLOGY:

• In this retrospective study, researchers identified 354,527 individuals diagnosed with COVID-19 via polymerase chain reaction (PCR) testing from Oct. 8, 2020, to Dec. 31, 2021.
• Researchers compared the COVID-19 group with 6,134,940 healthy individuals who had no evidence of COVID-19 to quantify the risk for autoimmune and autoinflammatory connective tissue disorders.
• Patients were followed until diagnosis, death, or end of study period (Dec. 31, 2021).

TAKEAWAY:

• Risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody–associated vasculitis, Crohn’s disease, and sarcoidosis were higher in the COVID-19 group.
• Patients with more severe COVID-19 (admitted to the ICU) were at greater risk for many autoimmune conditions, including alopecia totalis, psoriasis, vitiligo, and vasculitis.
•  

IN PRACTICE:

“Our results emphasize the need to focus on managing not only the acute stages of COVID-19 itself but also autoimmune diseases as complications of COVID-19,” the authors wrote.

SOURCE:

Sung Ha Lim, MD, of Yonsei University, Wonju, South Korea, was the first author of the study, published in JAMA Network Open.

LIMITATIONS:

The study was retrospective and was composed almost exclusively of individuals from a single ethnicity. The study could have included individuals with COVID-19 in the control group who did not undergo PCR testing. The analysis did not include detailed information on each patient, including genetic information, that could have contributed to autoimmune disease risk.

DISCLOSURES:

The study was supported by a fund from the research program of the Korea Medical Institute and by grants from the Korea Health Industry Development Institute, the Korean Ministry of Health & Welfare, and the National Research Foundation of Korea. The authors disclosed no relevant financial relationships.

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

The Food and Drug Administration has granted an interchangeability designation to adalimumab-afzb (Abrilada), according to an announcement from Pfizer.

This is the second adalimumab biosimilar granted interchangeability. The first, adalimumab-adbm (Cyltezo), became available in July.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Biosimilars introduce market competition that can help lower drug prices. Adalimumab-afzb is one of nine approved biosimilars for Humira, and the last to launch in 2023.

Adalimumab-afzb is indicated for:

• Adults with rheumatoid arthritis. 
• Polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
• Adults with psoriatic arthritis.
• Adults with ankylosing spondylitis.
• Crohn’s disease in adults and children 6 years of age and older.
• Adults with ulcerative colitis.
• Adults with plaque psoriasis.
• Adults with hidradenitis suppurativa.
• Adults with noninfectious intermediate and posterior uveitis and panuveitis.

“With this designation, Abrilada is now both biosimilar to and interchangeable with Humira, reinforcing confidence among physicians and pharmacists that there is no decrease in effectiveness or increase in safety risk associated with switching between Abrilada and the reference product,” Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas, said in Pfizer’s statement.

An interchangeability designation allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). To achieve this designation, Pfizer submitted data from a phase 3 study led by Dr. Fleischmann that evaluated adalimumab-afzb in patients with RA. Patients who were switched three times between the biosimilar and the reference product had outcomes similar to those of patients continuously treated with the reference product. 

Adalimumab-afzb will be available later in October at a 5% discount from Humira’s price. Later this year, the drug will launch at a second price, a 60% discount from Humira.

Full prescribing information for adalimumab-afzb is available here.

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

The Food and Drug Administration has granted an interchangeability designation to adalimumab-afzb (Abrilada), according to an announcement from Pfizer.

This is the second adalimumab biosimilar granted interchangeability. The first, adalimumab-adbm (Cyltezo), became available in July.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Biosimilars introduce market competition that can help lower drug prices. Adalimumab-afzb is one of nine approved biosimilars for Humira, and the last to launch in 2023.

Adalimumab-afzb is indicated for:

• Adults with rheumatoid arthritis. 
• Polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
• Adults with psoriatic arthritis.
• Adults with ankylosing spondylitis.
• Crohn’s disease in adults and children 6 years of age and older.
• Adults with ulcerative colitis.
• Adults with plaque psoriasis.
• Adults with hidradenitis suppurativa.
• Adults with noninfectious intermediate and posterior uveitis and panuveitis.

“With this designation, Abrilada is now both biosimilar to and interchangeable with Humira, reinforcing confidence among physicians and pharmacists that there is no decrease in effectiveness or increase in safety risk associated with switching between Abrilada and the reference product,” Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas, said in Pfizer’s statement.

An interchangeability designation allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). To achieve this designation, Pfizer submitted data from a phase 3 study led by Dr. Fleischmann that evaluated adalimumab-afzb in patients with RA. Patients who were switched three times between the biosimilar and the reference product had outcomes similar to those of patients continuously treated with the reference product. 

Adalimumab-afzb will be available later in October at a 5% discount from Humira’s price. Later this year, the drug will launch at a second price, a 60% discount from Humira.

Full prescribing information for adalimumab-afzb is available here.

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

The Food and Drug Administration has granted an interchangeability designation to adalimumab-afzb (Abrilada), according to an announcement from Pfizer.

This is the second adalimumab biosimilar granted interchangeability. The first, adalimumab-adbm (Cyltezo), became available in July.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Biosimilars introduce market competition that can help lower drug prices. Adalimumab-afzb is one of nine approved biosimilars for Humira, and the last to launch in 2023.

Adalimumab-afzb is indicated for:

• Adults with rheumatoid arthritis. 
• Polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
• Adults with psoriatic arthritis.
• Adults with ankylosing spondylitis.
• Crohn’s disease in adults and children 6 years of age and older.
• Adults with ulcerative colitis.
• Adults with plaque psoriasis.
• Adults with hidradenitis suppurativa.
• Adults with noninfectious intermediate and posterior uveitis and panuveitis.

“With this designation, Abrilada is now both biosimilar to and interchangeable with Humira, reinforcing confidence among physicians and pharmacists that there is no decrease in effectiveness or increase in safety risk associated with switching between Abrilada and the reference product,” Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas, said in Pfizer’s statement.

An interchangeability designation allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). To achieve this designation, Pfizer submitted data from a phase 3 study led by Dr. Fleischmann that evaluated adalimumab-afzb in patients with RA. Patients who were switched three times between the biosimilar and the reference product had outcomes similar to those of patients continuously treated with the reference product. 

Adalimumab-afzb will be available later in October at a 5% discount from Humira’s price. Later this year, the drug will launch at a second price, a 60% discount from Humira.

Full prescribing information for adalimumab-afzb is available here.

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

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that typically presents as a symmetric inflammatory polyarthritis (synovitis) primarily affecting the hands and feet. Any joint lined by a synovial membrane may be involved; however, extraarticular involvement of various organs can be significant. RA is theorized to develop when a genetically susceptible individual experiences an external trigger (e.g., cigarette smoking, infection, trauma) that precipitates an autoimmune reaction.

Rheumatology is a rapidly advancing, but relatively young, subspecialty. An understanding of the pathophysiology, treatment, and classification of RA is still emerging. Here are five things to know about RA.
 

1. A healthier lifestyle is associated with a reduced risk of developing RA. 

Large epidemiologic studies have identified several factors that increase the incidence of RA; these include an unhealthy diet, smoking, adiposity, low educational level, and low socioeconomic status. A patient’s response to antirheumatic medications can be affected by certain lifestyle habits, which can be associated with worse treatment outcomes; such habits include smoking, insufficient physical activity, and obesity, among others. Although methodologic problems may impede making firm conclusions regarding a causal role for these factors in the disease course and risk of developing RA, current evidence is sufficient to recommend quitting smoking, adopting a healthy diet, preventing obesity, and maintaining a high level of physical activity to support the effectiveness of current antirheumatic drugs.

In the Nurses’ Health Study, biennial questionnaires were used to collect lifestyle and medical information to determine which modifiable risk factors are associated with the risk for RA in women. Patient medical records were used to confirm incident RA and serostatus. The healthy lifestyle index score (HLIS), which includes five modifiable risk factors (smoking, alcohol consumption, body mass index, physical activity, and diet), was used to assess risk. Cox regression, which was adjusted for confounders, was used to model associations between HLIS and the incidence of RA. The study concluded that a healthier lifestyle was associated with a lower risk of developing RA, and a significant number of RA cases may be preventable if patients adopted four or more healthy lifestyle factors.

The Mediterranean diet is one current popular dietary option that appears to have promising evidence in many disease processes, including RA.

2. In pregnant women with RA, the course of the disease can change throughout pregnancy. 

The course of RA often changes during pregnancy. About half of pregnant women with RA have low disease activity, and 20%-40% achieve remission by the third trimester; however, nearly 20% have worse or moderate to high disease activity during pregnancy that may require further therapeutic intervention. Postpartum flares of RA also may occur, with studies reporting rates of 39%-90%.

No specific guidelines address obstetric monitoring in patients with RA. Because few data suggest a significantly increased risk for preterm birth, preeclampsia, or fetal growth restriction, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

Medications considered to be low risk in pregnancy include low-dose corticosteroids, antimalarial agents, sulfasalazine, and azathioprine. Certain tumor necrosis factor inhibitors are also thought to be relatively safe.

3. A well-designed exercise program can be beneficial in RA.

Regular physical activity has replaced bed rest as the recommended response to the stiffness and pain associated with RA. However, many patients who have RA do not really believe this. Lack of conviction and motivation appear to be the major factors that deter nearly half of patients with RA from moving about enough to help their situation. There is ample evidence about the benefits of physical activity in RA, but little research into why few patients with RA take advantage of it. The extreme physical inactivity of patients with RA becomes a vicious cycle in terms of health and disease progression. Thus, encouraging physical activity is an essential part of the overall treatment of RA.

Findings from randomized controlled trials show that exercise is fundamentally beneficial for patients with RA. The benefits of properly designed physical exercise programs include improved cardiorespiratory fitness and cardiovascular health, increased muscle mass, reduced adiposity, increased strength, and improved physical functioning, all achieved without exacerbation of disease activity or joint damage.

The American College of Rheumatology (ACR) has released recommendations for exercise interventions for RA. The ACR strongly recommends consistent engagement in an exercise program over no exercise. The type of exercise is open to interpretation. An exercise program for patients with rheumatic diseases aims to preserve or restore the range of motion of affected joints, increase muscle strength and endurance, and improve mood and decrease health risks associated with a sedentary lifestyle.

4. RA is a systemic disease that affects multiple organ systems.

Although synovitis is the pathologic hallmark of RA, extraarticular manifestations and comorbidities occur presumably owing to the complex, chronic, inflammatory, and autoimmune features of RA.

The most common cause of death in patients with RA is cardiovascular disease. Compared with the general population, patients with RA have two times the risk of having a myocardial infarction, and they have up to 50% greater cardiovascular mortality risk. Factors identified to play important roles in atherosclerotic damage and incident cardiovascular disease include severe and prolonged disease activity, inflammation (e.g., C-reactive protein, anti–citrullinated protein antibodies (ACPAs), cytokines, matrix-degrading enzymes), and genetics.

Respiratory disease is the second major cause of death in patients with RA; this occurs in 30%-40% of patients with RA. The lung interstitium, airways, and pleurae can all be affected by RA, but pulmonary vascular involvement is less common.

Central and peripheral nervous system involvement is typically attributed to RA-associated small-vessel vasculitis, joint damage, and/or drug toxicity. Evidence also suggests that systemic inflammation causes microvascular cerebral damage that is associated with the development of vascular dementia and Alzheimer’s disease. Finally, some observational studies have suggested that drugs commonly used to treat RA – disease-modifying antirheumatic drugs (DMARDs) and biologics – may reduce the incidence of dementia.

5. As treatment options for RA improve, many controversies have arisen.

In patients without RA symptoms but with biomarkers, experts debate whether early treatment with DMARDs could prevent irreversible joint damage.

There is no clear definition of pre-RA, but it could be defined as having positive markers for RA (e.g., positive rheumatoid factor and anti–cyclic citrullinated peptides) or having joint pain with abnormal ultrasonography findings but not having positive biomarkers. However, not all patients who have positive biomarkers progress to clinical RA, so what exactly determines this progression is unclear. Nevertheless, some clinicians do treat pre-RA. This was a major debate at the ACR’s 2022 meeting.

Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients. Lifestyle interventions in these patients, including exercise, weight control, and cardiovascular health, may not prevent disease but may delay the onset of full-blown clinical RA.

The discovery of pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent RA in at-risk individuals. Additional studies are evaluating the ability of drugs, including abatacept, hydroxychloroquine, and methotrexate, to prevent or delay future RA.

Dual biologics target different pathways – ostensibly boosting efficacy – but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. Overall, there is a paucity of data concerning the safety of the simultaneous use of more than one biologic. Dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used at physicians’ discretion requires close monitoring of patients, with an emphasis on the safety profile.

Large language models (artificial intelligence [AI]) are rapidly taking hold in medicine. Many argue that they can enrich patient care, but they come with liability risks.

Large language models, such as AI chatbots or ChatGPT, can increase access to information, help with patient education, and support decision-making. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large language models in health care is fraught with ethical and legal concerns.

Liability issues can arise if errors, inaccuracies, or adverse outcomes result from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process.

To mitigate liability risks, AI chatbots in rheumatology must comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help to minimize liability concerns.

The benefits and risks associated with tapering DMARD therapy in patients with RA who have sustained remission of disease should be considered.

Although some patients with well-controlled RA have relapse after tapering or discontinuing DMARDs, some do not, making this treatment strategy a personal decision undertaken with a rheumatologist.

In the RETRO study, German researchers examined the effects of tapering or stopping DMARDs in patients whose RA was in sustained remission. In the phase 3 trial (n = 316), investigators randomized 303 patients with remission for ≥ 6 months who were on stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose, (2) tapering to 50% of the DMARD dose, and (3) 50% tapering followed by DMARD withdrawal. The proportion of patients who continued in remission at 1 year was 81.2% in group 1, 58.6% in group 2, and 43.3% in group 3. Predictors for flare-ups were female sex, longer disease duration, rheumatoid factor or ACPA positivity, and higher disease activity scores at baseline.

The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

The interplay between long COVID and RA is a recent phenomenon that needs to be considered.

RA shares similar symptoms with long COVID. Patients with a history of RA and a previous diagnosis of COVID-19 who have developed persistent joint or muscle symptoms pose a significant challenge to clinicians. Such patients may be experiencing long COVID or a flare-up of their preexisting rheumatic disease.

Immunosuppressive medications can potentially increase the risk for COVID-19, but it is not clear how they affect disease severity risk. Individuals with RA and long COVID need careful evaluation to balance the management of disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections.

Dr. Dombrosky is a staff physician in rheumatology at Central Virginia VA Health Care System in Richmond. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that typically presents as a symmetric inflammatory polyarthritis (synovitis) primarily affecting the hands and feet. Any joint lined by a synovial membrane may be involved; however, extraarticular involvement of various organs can be significant. RA is theorized to develop when a genetically susceptible individual experiences an external trigger (e.g., cigarette smoking, infection, trauma) that precipitates an autoimmune reaction.

Rheumatology is a rapidly advancing, but relatively young, subspecialty. An understanding of the pathophysiology, treatment, and classification of RA is still emerging. Here are five things to know about RA.
 

1. A healthier lifestyle is associated with a reduced risk of developing RA. 

Large epidemiologic studies have identified several factors that increase the incidence of RA; these include an unhealthy diet, smoking, adiposity, low educational level, and low socioeconomic status. A patient’s response to antirheumatic medications can be affected by certain lifestyle habits, which can be associated with worse treatment outcomes; such habits include smoking, insufficient physical activity, and obesity, among others. Although methodologic problems may impede making firm conclusions regarding a causal role for these factors in the disease course and risk of developing RA, current evidence is sufficient to recommend quitting smoking, adopting a healthy diet, preventing obesity, and maintaining a high level of physical activity to support the effectiveness of current antirheumatic drugs.

In the Nurses’ Health Study, biennial questionnaires were used to collect lifestyle and medical information to determine which modifiable risk factors are associated with the risk for RA in women. Patient medical records were used to confirm incident RA and serostatus. The healthy lifestyle index score (HLIS), which includes five modifiable risk factors (smoking, alcohol consumption, body mass index, physical activity, and diet), was used to assess risk. Cox regression, which was adjusted for confounders, was used to model associations between HLIS and the incidence of RA. The study concluded that a healthier lifestyle was associated with a lower risk of developing RA, and a significant number of RA cases may be preventable if patients adopted four or more healthy lifestyle factors.

The Mediterranean diet is one current popular dietary option that appears to have promising evidence in many disease processes, including RA.

2. In pregnant women with RA, the course of the disease can change throughout pregnancy. 

The course of RA often changes during pregnancy. About half of pregnant women with RA have low disease activity, and 20%-40% achieve remission by the third trimester; however, nearly 20% have worse or moderate to high disease activity during pregnancy that may require further therapeutic intervention. Postpartum flares of RA also may occur, with studies reporting rates of 39%-90%.

No specific guidelines address obstetric monitoring in patients with RA. Because few data suggest a significantly increased risk for preterm birth, preeclampsia, or fetal growth restriction, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

Medications considered to be low risk in pregnancy include low-dose corticosteroids, antimalarial agents, sulfasalazine, and azathioprine. Certain tumor necrosis factor inhibitors are also thought to be relatively safe.

3. A well-designed exercise program can be beneficial in RA.

Regular physical activity has replaced bed rest as the recommended response to the stiffness and pain associated with RA. However, many patients who have RA do not really believe this. Lack of conviction and motivation appear to be the major factors that deter nearly half of patients with RA from moving about enough to help their situation. There is ample evidence about the benefits of physical activity in RA, but little research into why few patients with RA take advantage of it. The extreme physical inactivity of patients with RA becomes a vicious cycle in terms of health and disease progression. Thus, encouraging physical activity is an essential part of the overall treatment of RA.

Findings from randomized controlled trials show that exercise is fundamentally beneficial for patients with RA. The benefits of properly designed physical exercise programs include improved cardiorespiratory fitness and cardiovascular health, increased muscle mass, reduced adiposity, increased strength, and improved physical functioning, all achieved without exacerbation of disease activity or joint damage.

The American College of Rheumatology (ACR) has released recommendations for exercise interventions for RA. The ACR strongly recommends consistent engagement in an exercise program over no exercise. The type of exercise is open to interpretation. An exercise program for patients with rheumatic diseases aims to preserve or restore the range of motion of affected joints, increase muscle strength and endurance, and improve mood and decrease health risks associated with a sedentary lifestyle.

4. RA is a systemic disease that affects multiple organ systems.

Although synovitis is the pathologic hallmark of RA, extraarticular manifestations and comorbidities occur presumably owing to the complex, chronic, inflammatory, and autoimmune features of RA.

The most common cause of death in patients with RA is cardiovascular disease. Compared with the general population, patients with RA have two times the risk of having a myocardial infarction, and they have up to 50% greater cardiovascular mortality risk. Factors identified to play important roles in atherosclerotic damage and incident cardiovascular disease include severe and prolonged disease activity, inflammation (e.g., C-reactive protein, anti–citrullinated protein antibodies (ACPAs), cytokines, matrix-degrading enzymes), and genetics.

Respiratory disease is the second major cause of death in patients with RA; this occurs in 30%-40% of patients with RA. The lung interstitium, airways, and pleurae can all be affected by RA, but pulmonary vascular involvement is less common.

Central and peripheral nervous system involvement is typically attributed to RA-associated small-vessel vasculitis, joint damage, and/or drug toxicity. Evidence also suggests that systemic inflammation causes microvascular cerebral damage that is associated with the development of vascular dementia and Alzheimer’s disease. Finally, some observational studies have suggested that drugs commonly used to treat RA – disease-modifying antirheumatic drugs (DMARDs) and biologics – may reduce the incidence of dementia.

5. As treatment options for RA improve, many controversies have arisen.

In patients without RA symptoms but with biomarkers, experts debate whether early treatment with DMARDs could prevent irreversible joint damage.

There is no clear definition of pre-RA, but it could be defined as having positive markers for RA (e.g., positive rheumatoid factor and anti–cyclic citrullinated peptides) or having joint pain with abnormal ultrasonography findings but not having positive biomarkers. However, not all patients who have positive biomarkers progress to clinical RA, so what exactly determines this progression is unclear. Nevertheless, some clinicians do treat pre-RA. This was a major debate at the ACR’s 2022 meeting.

Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients. Lifestyle interventions in these patients, including exercise, weight control, and cardiovascular health, may not prevent disease but may delay the onset of full-blown clinical RA.

The discovery of pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent RA in at-risk individuals. Additional studies are evaluating the ability of drugs, including abatacept, hydroxychloroquine, and methotrexate, to prevent or delay future RA.

Dual biologics target different pathways – ostensibly boosting efficacy – but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. Overall, there is a paucity of data concerning the safety of the simultaneous use of more than one biologic. Dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used at physicians’ discretion requires close monitoring of patients, with an emphasis on the safety profile.

Large language models (artificial intelligence [AI]) are rapidly taking hold in medicine. Many argue that they can enrich patient care, but they come with liability risks.

Large language models, such as AI chatbots or ChatGPT, can increase access to information, help with patient education, and support decision-making. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large language models in health care is fraught with ethical and legal concerns.

Liability issues can arise if errors, inaccuracies, or adverse outcomes result from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process.

To mitigate liability risks, AI chatbots in rheumatology must comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help to minimize liability concerns.

The benefits and risks associated with tapering DMARD therapy in patients with RA who have sustained remission of disease should be considered.

Although some patients with well-controlled RA have relapse after tapering or discontinuing DMARDs, some do not, making this treatment strategy a personal decision undertaken with a rheumatologist.

In the RETRO study, German researchers examined the effects of tapering or stopping DMARDs in patients whose RA was in sustained remission. In the phase 3 trial (n = 316), investigators randomized 303 patients with remission for ≥ 6 months who were on stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose, (2) tapering to 50% of the DMARD dose, and (3) 50% tapering followed by DMARD withdrawal. The proportion of patients who continued in remission at 1 year was 81.2% in group 1, 58.6% in group 2, and 43.3% in group 3. Predictors for flare-ups were female sex, longer disease duration, rheumatoid factor or ACPA positivity, and higher disease activity scores at baseline.

The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

The interplay between long COVID and RA is a recent phenomenon that needs to be considered.

RA shares similar symptoms with long COVID. Patients with a history of RA and a previous diagnosis of COVID-19 who have developed persistent joint or muscle symptoms pose a significant challenge to clinicians. Such patients may be experiencing long COVID or a flare-up of their preexisting rheumatic disease.

Immunosuppressive medications can potentially increase the risk for COVID-19, but it is not clear how they affect disease severity risk. Individuals with RA and long COVID need careful evaluation to balance the management of disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections.

Dr. Dombrosky is a staff physician in rheumatology at Central Virginia VA Health Care System in Richmond. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that typically presents as a symmetric inflammatory polyarthritis (synovitis) primarily affecting the hands and feet. Any joint lined by a synovial membrane may be involved; however, extraarticular involvement of various organs can be significant. RA is theorized to develop when a genetically susceptible individual experiences an external trigger (e.g., cigarette smoking, infection, trauma) that precipitates an autoimmune reaction.

Rheumatology is a rapidly advancing, but relatively young, subspecialty. An understanding of the pathophysiology, treatment, and classification of RA is still emerging. Here are five things to know about RA.
 

1. A healthier lifestyle is associated with a reduced risk of developing RA. 

Large epidemiologic studies have identified several factors that increase the incidence of RA; these include an unhealthy diet, smoking, adiposity, low educational level, and low socioeconomic status. A patient’s response to antirheumatic medications can be affected by certain lifestyle habits, which can be associated with worse treatment outcomes; such habits include smoking, insufficient physical activity, and obesity, among others. Although methodologic problems may impede making firm conclusions regarding a causal role for these factors in the disease course and risk of developing RA, current evidence is sufficient to recommend quitting smoking, adopting a healthy diet, preventing obesity, and maintaining a high level of physical activity to support the effectiveness of current antirheumatic drugs.

In the Nurses’ Health Study, biennial questionnaires were used to collect lifestyle and medical information to determine which modifiable risk factors are associated with the risk for RA in women. Patient medical records were used to confirm incident RA and serostatus. The healthy lifestyle index score (HLIS), which includes five modifiable risk factors (smoking, alcohol consumption, body mass index, physical activity, and diet), was used to assess risk. Cox regression, which was adjusted for confounders, was used to model associations between HLIS and the incidence of RA. The study concluded that a healthier lifestyle was associated with a lower risk of developing RA, and a significant number of RA cases may be preventable if patients adopted four or more healthy lifestyle factors.

The Mediterranean diet is one current popular dietary option that appears to have promising evidence in many disease processes, including RA.

2. In pregnant women with RA, the course of the disease can change throughout pregnancy. 

The course of RA often changes during pregnancy. About half of pregnant women with RA have low disease activity, and 20%-40% achieve remission by the third trimester; however, nearly 20% have worse or moderate to high disease activity during pregnancy that may require further therapeutic intervention. Postpartum flares of RA also may occur, with studies reporting rates of 39%-90%.

No specific guidelines address obstetric monitoring in patients with RA. Because few data suggest a significantly increased risk for preterm birth, preeclampsia, or fetal growth restriction, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

Medications considered to be low risk in pregnancy include low-dose corticosteroids, antimalarial agents, sulfasalazine, and azathioprine. Certain tumor necrosis factor inhibitors are also thought to be relatively safe.

3. A well-designed exercise program can be beneficial in RA.

Regular physical activity has replaced bed rest as the recommended response to the stiffness and pain associated with RA. However, many patients who have RA do not really believe this. Lack of conviction and motivation appear to be the major factors that deter nearly half of patients with RA from moving about enough to help their situation. There is ample evidence about the benefits of physical activity in RA, but little research into why few patients with RA take advantage of it. The extreme physical inactivity of patients with RA becomes a vicious cycle in terms of health and disease progression. Thus, encouraging physical activity is an essential part of the overall treatment of RA.

Findings from randomized controlled trials show that exercise is fundamentally beneficial for patients with RA. The benefits of properly designed physical exercise programs include improved cardiorespiratory fitness and cardiovascular health, increased muscle mass, reduced adiposity, increased strength, and improved physical functioning, all achieved without exacerbation of disease activity or joint damage.

The American College of Rheumatology (ACR) has released recommendations for exercise interventions for RA. The ACR strongly recommends consistent engagement in an exercise program over no exercise. The type of exercise is open to interpretation. An exercise program for patients with rheumatic diseases aims to preserve or restore the range of motion of affected joints, increase muscle strength and endurance, and improve mood and decrease health risks associated with a sedentary lifestyle.

4. RA is a systemic disease that affects multiple organ systems.

Although synovitis is the pathologic hallmark of RA, extraarticular manifestations and comorbidities occur presumably owing to the complex, chronic, inflammatory, and autoimmune features of RA.

The most common cause of death in patients with RA is cardiovascular disease. Compared with the general population, patients with RA have two times the risk of having a myocardial infarction, and they have up to 50% greater cardiovascular mortality risk. Factors identified to play important roles in atherosclerotic damage and incident cardiovascular disease include severe and prolonged disease activity, inflammation (e.g., C-reactive protein, anti–citrullinated protein antibodies (ACPAs), cytokines, matrix-degrading enzymes), and genetics.

Respiratory disease is the second major cause of death in patients with RA; this occurs in 30%-40% of patients with RA. The lung interstitium, airways, and pleurae can all be affected by RA, but pulmonary vascular involvement is less common.

Central and peripheral nervous system involvement is typically attributed to RA-associated small-vessel vasculitis, joint damage, and/or drug toxicity. Evidence also suggests that systemic inflammation causes microvascular cerebral damage that is associated with the development of vascular dementia and Alzheimer’s disease. Finally, some observational studies have suggested that drugs commonly used to treat RA – disease-modifying antirheumatic drugs (DMARDs) and biologics – may reduce the incidence of dementia.

5. As treatment options for RA improve, many controversies have arisen.

In patients without RA symptoms but with biomarkers, experts debate whether early treatment with DMARDs could prevent irreversible joint damage.

There is no clear definition of pre-RA, but it could be defined as having positive markers for RA (e.g., positive rheumatoid factor and anti–cyclic citrullinated peptides) or having joint pain with abnormal ultrasonography findings but not having positive biomarkers. However, not all patients who have positive biomarkers progress to clinical RA, so what exactly determines this progression is unclear. Nevertheless, some clinicians do treat pre-RA. This was a major debate at the ACR’s 2022 meeting.

Studies have shown that early treatment of RA, including during the preclinical phase, can lead to better long-term outcomes. It can help reduce joint inflammation, control disease activity, and prevent or minimize irreversible joint damage. Early treatment also increases the likelihood of achieving remission or low disease activity, which improves quality of life for patients. Lifestyle interventions in these patients, including exercise, weight control, and cardiovascular health, may not prevent disease but may delay the onset of full-blown clinical RA.

The discovery of pre-RA has also underpinned the development of several clinical prevention trials in RA; specifically, the PRAIRI study demonstrated that a single dose of rituximab can delay the onset of clinically apparent RA in at-risk individuals. Additional studies are evaluating the ability of drugs, including abatacept, hydroxychloroquine, and methotrexate, to prevent or delay future RA.

Dual biologics target different pathways – ostensibly boosting efficacy – but unknowns, concerns over safety, and lack of evidence make the practice controversial.

Several randomized controlled trials have assessed the safety and efficacy of dual-biologic treatment of RA, but the results have been mixed, which has raised safety concerns. Overall, there is a paucity of data concerning the safety of the simultaneous use of more than one biologic. Dual therapy may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed. In the meantime, dual biologic therapy used at physicians’ discretion requires close monitoring of patients, with an emphasis on the safety profile.

Large language models (artificial intelligence [AI]) are rapidly taking hold in medicine. Many argue that they can enrich patient care, but they come with liability risks.

Large language models, such as AI chatbots or ChatGPT, can increase access to information, help with patient education, and support decision-making. Limitations include lack of personalization, clinical experience, and emotional connection. The use of large language models in health care is fraught with ethical and legal concerns.

Liability issues can arise if errors, inaccuracies, or adverse outcomes result from the use of AI chatbots. Determining liability may involve assessing factors such as the design and development of the AI system, training and deployment of the model, the communication of limitations and disclaimers to users, and the involvement of human healthcare professionals in the decision-making process.

To mitigate liability risks, AI chatbots in rheumatology must comply with applicable regulations and guidelines. Transparency in the capabilities and limitations of the system, clear communication of the boundaries of its advice, and the presence of human oversight are essential. Collaborating with legal experts and following best practices in the development and deployment of AI technologies can help to minimize liability concerns.

The benefits and risks associated with tapering DMARD therapy in patients with RA who have sustained remission of disease should be considered.

Although some patients with well-controlled RA have relapse after tapering or discontinuing DMARDs, some do not, making this treatment strategy a personal decision undertaken with a rheumatologist.

In the RETRO study, German researchers examined the effects of tapering or stopping DMARDs in patients whose RA was in sustained remission. In the phase 3 trial (n = 316), investigators randomized 303 patients with remission for ≥ 6 months who were on stable conventional synthetic or biologic DMARD treatment into three groups: (1) continuation on 100% DMARD dose, (2) tapering to 50% of the DMARD dose, and (3) 50% tapering followed by DMARD withdrawal. The proportion of patients who continued in remission at 1 year was 81.2% in group 1, 58.6% in group 2, and 43.3% in group 3. Predictors for flare-ups were female sex, longer disease duration, rheumatoid factor or ACPA positivity, and higher disease activity scores at baseline.

The abrupt cessation or reduction of DMARDs without medical supervision and guidance can exacerbate symptoms and result in disease flares.

The interplay between long COVID and RA is a recent phenomenon that needs to be considered.

RA shares similar symptoms with long COVID. Patients with a history of RA and a previous diagnosis of COVID-19 who have developed persistent joint or muscle symptoms pose a significant challenge to clinicians. Such patients may be experiencing long COVID or a flare-up of their preexisting rheumatic disease.

Immunosuppressive medications can potentially increase the risk for COVID-19, but it is not clear how they affect disease severity risk. Individuals with RA and long COVID need careful evaluation to balance the management of disease activity while considering the risks associated with immunosuppression and potential susceptibility to viral infections.

Dr. Dombrosky is a staff physician in rheumatology at Central Virginia VA Health Care System in Richmond. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PET scans may serve as both a diagnostic and prognostic tool in giant cell arteritis (GCA), according to a new study.

In over 100 patients with GCA who underwent 18F-fluorodeoxyglucose PET imaging, those with elevated FDG uptake at diagnosis were more likely to develop thoracic aortic aneurysms.

“PET-CT has an excellent diagnostic accuracy for the diagnosis of GCA, certainly if both extracranial and intracranial vessels were assessed. This study shows that performing PET imaging at diagnosis in patients with GCA may also help estimate the future risk for aortic aneurysm formation,” lead author Lien Moreel, MD, of the department of internal medicine at University Hospitals Leuven (Belgium), wrote in an email. “PET imaging at diagnosis can provide both diagnostic and prognostic information in one imaging tool in patients with GCA.”

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Previous retrospective studies have found an association between FDG uptake at diagnosis and risk for aortic complications, but “prospective studies confirming these findings are lacking,” the investigators wrote. The study was published online in Annals of Internal Medicine.

In the study, Dr. Moreel and colleagues prospectively followed 106 individuals diagnosed with GCA who received FDG-PET within 3 days after starting glucocorticoids. Patients also had CT imaging at diagnosis and then CT imaging annually for up to 10 years. 

A PET scan was considered positive with an FDG uptake of grade 2 or higher in any of seven vascular regions (thoracic and abdominal aorta, subclavian, axillary, carotid, iliac, and femoral arteries). Researchers also used the results to quantify a total vascular score (TVS). Out of the entire cohort, 75 patients had a positive PET scan result.

These patients had a larger increase in the diameter of the ascending aorta and the descending aorta, as well the volume of thoracic aorta after 5 years, compared with those who had a negative PET scan result. These changes were also associated with higher TVS at diagnosis. Of the 23 patients who developed an aortic aneurysm, 18 had a positive PET scan at diagnosis.

The risk of incident thoracic aortic aneurysms was calculated to be 10 times higher in patients with positive PET scans. Fourteen of the 15 patients (93%) with an incident thoracic aortic aneurysm had positive PET results.

Up to now, “we’ve had no way of predicting which patients might be at risk of this potentially serious complication,” Kenneth Warrington, MD, chair of the department of rheumatology and director of the Vasculitis Clinic at the Mayo Clinic in Rochester, Minn., said in an interview. He was not involved with the research.

He hopes that the findings will help inform clinicians on how patients with GCA should be evaluated and monitored. Although the American College of Rheumatology conditionally recommends noninvasive imaging in patients newly diagnosed with GCA, guidance for follow-up on these patients is less clear.

“There are no clear guidelines, but most clinicians who take care of patients with GCA do obtain imaging periodically,” he said. “There is a lot of variability in the practice in terms of which type of scan is used and how often it’s done.”

Although this study did not specifically look at the benefit of screening patients, “we think that follow-up of aortic dimensions seems to be warranted in GCA patients with a positive PET scan result, especially in those with high intensity and broad extent of vascular inflammation,” Dr. Moreel said. “However, the added value of screening and the interval required should be addressed in future studies.”

Applying this study’s protocol in practice in the United States might be difficult, Dr. Warrington noted, as it can be challenging logistically to get imaging done within 3 days of starting steroids. However, Dr. Moreel said it is possible to delay the start of glucocorticoids until the PET scan is performed in patients without visual symptoms or jaw claudication.

PET scans are also expensive, and it can be difficult to get insurance coverage in the United States. However, other imaging modalities could potentially be used in similar ways, Dr. Warrington said. “One could potentially extrapolate to say that if there is difficulty with accessing PET scan, we could use other modalities like CT or MRI basically to see whether the aorta is inflamed or not.”

Dr. Moreel disclosed no relevant financial relationships. Dr. Warrington has received compensation for consulting activities with Sanofi. Eli Lilly, Kiniksa, and Bristol-Myers Squibb have provided support to the Mayo Clinic for clinical trials related to GCA, of which Dr. Warrington served as subinvestigator.

A version of this article appeared on Medscape.com.

PET scans may serve as both a diagnostic and prognostic tool in giant cell arteritis (GCA), according to a new study.

In over 100 patients with GCA who underwent 18F-fluorodeoxyglucose PET imaging, those with elevated FDG uptake at diagnosis were more likely to develop thoracic aortic aneurysms.

“PET-CT has an excellent diagnostic accuracy for the diagnosis of GCA, certainly if both extracranial and intracranial vessels were assessed. This study shows that performing PET imaging at diagnosis in patients with GCA may also help estimate the future risk for aortic aneurysm formation,” lead author Lien Moreel, MD, of the department of internal medicine at University Hospitals Leuven (Belgium), wrote in an email. “PET imaging at diagnosis can provide both diagnostic and prognostic information in one imaging tool in patients with GCA.”

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Previous retrospective studies have found an association between FDG uptake at diagnosis and risk for aortic complications, but “prospective studies confirming these findings are lacking,” the investigators wrote. The study was published online in Annals of Internal Medicine.

In the study, Dr. Moreel and colleagues prospectively followed 106 individuals diagnosed with GCA who received FDG-PET within 3 days after starting glucocorticoids. Patients also had CT imaging at diagnosis and then CT imaging annually for up to 10 years. 

A PET scan was considered positive with an FDG uptake of grade 2 or higher in any of seven vascular regions (thoracic and abdominal aorta, subclavian, axillary, carotid, iliac, and femoral arteries). Researchers also used the results to quantify a total vascular score (TVS). Out of the entire cohort, 75 patients had a positive PET scan result.

These patients had a larger increase in the diameter of the ascending aorta and the descending aorta, as well the volume of thoracic aorta after 5 years, compared with those who had a negative PET scan result. These changes were also associated with higher TVS at diagnosis. Of the 23 patients who developed an aortic aneurysm, 18 had a positive PET scan at diagnosis.

The risk of incident thoracic aortic aneurysms was calculated to be 10 times higher in patients with positive PET scans. Fourteen of the 15 patients (93%) with an incident thoracic aortic aneurysm had positive PET results.

Up to now, “we’ve had no way of predicting which patients might be at risk of this potentially serious complication,” Kenneth Warrington, MD, chair of the department of rheumatology and director of the Vasculitis Clinic at the Mayo Clinic in Rochester, Minn., said in an interview. He was not involved with the research.

He hopes that the findings will help inform clinicians on how patients with GCA should be evaluated and monitored. Although the American College of Rheumatology conditionally recommends noninvasive imaging in patients newly diagnosed with GCA, guidance for follow-up on these patients is less clear.

“There are no clear guidelines, but most clinicians who take care of patients with GCA do obtain imaging periodically,” he said. “There is a lot of variability in the practice in terms of which type of scan is used and how often it’s done.”

Although this study did not specifically look at the benefit of screening patients, “we think that follow-up of aortic dimensions seems to be warranted in GCA patients with a positive PET scan result, especially in those with high intensity and broad extent of vascular inflammation,” Dr. Moreel said. “However, the added value of screening and the interval required should be addressed in future studies.”

Applying this study’s protocol in practice in the United States might be difficult, Dr. Warrington noted, as it can be challenging logistically to get imaging done within 3 days of starting steroids. However, Dr. Moreel said it is possible to delay the start of glucocorticoids until the PET scan is performed in patients without visual symptoms or jaw claudication.

PET scans are also expensive, and it can be difficult to get insurance coverage in the United States. However, other imaging modalities could potentially be used in similar ways, Dr. Warrington said. “One could potentially extrapolate to say that if there is difficulty with accessing PET scan, we could use other modalities like CT or MRI basically to see whether the aorta is inflamed or not.”

Dr. Moreel disclosed no relevant financial relationships. Dr. Warrington has received compensation for consulting activities with Sanofi. Eli Lilly, Kiniksa, and Bristol-Myers Squibb have provided support to the Mayo Clinic for clinical trials related to GCA, of which Dr. Warrington served as subinvestigator.

A version of this article appeared on Medscape.com.

PET scans may serve as both a diagnostic and prognostic tool in giant cell arteritis (GCA), according to a new study.

In over 100 patients with GCA who underwent 18F-fluorodeoxyglucose PET imaging, those with elevated FDG uptake at diagnosis were more likely to develop thoracic aortic aneurysms.

“PET-CT has an excellent diagnostic accuracy for the diagnosis of GCA, certainly if both extracranial and intracranial vessels were assessed. This study shows that performing PET imaging at diagnosis in patients with GCA may also help estimate the future risk for aortic aneurysm formation,” lead author Lien Moreel, MD, of the department of internal medicine at University Hospitals Leuven (Belgium), wrote in an email. “PET imaging at diagnosis can provide both diagnostic and prognostic information in one imaging tool in patients with GCA.”

Brudersohn/CC BY-SA 3.0/Wikimedia Commons

Previous retrospective studies have found an association between FDG uptake at diagnosis and risk for aortic complications, but “prospective studies confirming these findings are lacking,” the investigators wrote. The study was published online in Annals of Internal Medicine.

In the study, Dr. Moreel and colleagues prospectively followed 106 individuals diagnosed with GCA who received FDG-PET within 3 days after starting glucocorticoids. Patients also had CT imaging at diagnosis and then CT imaging annually for up to 10 years. 

A PET scan was considered positive with an FDG uptake of grade 2 or higher in any of seven vascular regions (thoracic and abdominal aorta, subclavian, axillary, carotid, iliac, and femoral arteries). Researchers also used the results to quantify a total vascular score (TVS). Out of the entire cohort, 75 patients had a positive PET scan result.

These patients had a larger increase in the diameter of the ascending aorta and the descending aorta, as well the volume of thoracic aorta after 5 years, compared with those who had a negative PET scan result. These changes were also associated with higher TVS at diagnosis. Of the 23 patients who developed an aortic aneurysm, 18 had a positive PET scan at diagnosis.

The risk of incident thoracic aortic aneurysms was calculated to be 10 times higher in patients with positive PET scans. Fourteen of the 15 patients (93%) with an incident thoracic aortic aneurysm had positive PET results.

Up to now, “we’ve had no way of predicting which patients might be at risk of this potentially serious complication,” Kenneth Warrington, MD, chair of the department of rheumatology and director of the Vasculitis Clinic at the Mayo Clinic in Rochester, Minn., said in an interview. He was not involved with the research.

He hopes that the findings will help inform clinicians on how patients with GCA should be evaluated and monitored. Although the American College of Rheumatology conditionally recommends noninvasive imaging in patients newly diagnosed with GCA, guidance for follow-up on these patients is less clear.

“There are no clear guidelines, but most clinicians who take care of patients with GCA do obtain imaging periodically,” he said. “There is a lot of variability in the practice in terms of which type of scan is used and how often it’s done.”

Although this study did not specifically look at the benefit of screening patients, “we think that follow-up of aortic dimensions seems to be warranted in GCA patients with a positive PET scan result, especially in those with high intensity and broad extent of vascular inflammation,” Dr. Moreel said. “However, the added value of screening and the interval required should be addressed in future studies.”

Applying this study’s protocol in practice in the United States might be difficult, Dr. Warrington noted, as it can be challenging logistically to get imaging done within 3 days of starting steroids. However, Dr. Moreel said it is possible to delay the start of glucocorticoids until the PET scan is performed in patients without visual symptoms or jaw claudication.

PET scans are also expensive, and it can be difficult to get insurance coverage in the United States. However, other imaging modalities could potentially be used in similar ways, Dr. Warrington said. “One could potentially extrapolate to say that if there is difficulty with accessing PET scan, we could use other modalities like CT or MRI basically to see whether the aorta is inflamed or not.”

Dr. Moreel disclosed no relevant financial relationships. Dr. Warrington has received compensation for consulting activities with Sanofi. Eli Lilly, Kiniksa, and Bristol-Myers Squibb have provided support to the Mayo Clinic for clinical trials related to GCA, of which Dr. Warrington served as subinvestigator.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved the biosimilar tocilizumab-bavi (Tofidence), Biogen, the drug’s manufacturer, announced on Sept. 29.

It is the first tocilizumab biosimilar approved by the FDA. The reference product, Actemra (Genentech), was first approved by the agency in 2010.

“The approval of Tofidence in the U.S. marks another positive step toward helping more people with chronic autoimmune conditions gain access to leading therapies,” Ian Henshaw, global head of biosimilars at Biogen, said in a statement. “With the increasing numbers of approved biosimilars, we expect increased savings and sustainability for health care systems and an increase in physician choice and patient access to biologics.”

Biogen’s pricing for tocilizumab-bavi will be available closer to the product’s launch date, which has yet to be determined, a company spokesman said. The U.S. average monthly cost of Actemra for rheumatoid arthritis, administered intravenously, is $2,134-$4,268 depending on dosage, according to a Genentech spokesperson.

Tocilizumab-bavi is an intravenous formulation (20 mg/mL) indicated for treatment of moderately to severely active RA, polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). The medication is administered every 4 weeks in RA and PJIA and every 8 weeks in SJIA as a single intravenous drip infusion over 1 hour.

The European Commission approved its first tocilizumab biosimilar, Tyenne (Fresenius Kabi), earlier in 2023 in both subcutaneous and intravenous formulations. Biogen did not comment on whether the company is working on a subcutaneous formulation for tocilizumab-bavi.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved the biosimilar tocilizumab-bavi (Tofidence), Biogen, the drug’s manufacturer, announced on Sept. 29.

It is the first tocilizumab biosimilar approved by the FDA. The reference product, Actemra (Genentech), was first approved by the agency in 2010.

“The approval of Tofidence in the U.S. marks another positive step toward helping more people with chronic autoimmune conditions gain access to leading therapies,” Ian Henshaw, global head of biosimilars at Biogen, said in a statement. “With the increasing numbers of approved biosimilars, we expect increased savings and sustainability for health care systems and an increase in physician choice and patient access to biologics.”

Biogen’s pricing for tocilizumab-bavi will be available closer to the product’s launch date, which has yet to be determined, a company spokesman said. The U.S. average monthly cost of Actemra for rheumatoid arthritis, administered intravenously, is $2,134-$4,268 depending on dosage, according to a Genentech spokesperson.

Tocilizumab-bavi is an intravenous formulation (20 mg/mL) indicated for treatment of moderately to severely active RA, polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). The medication is administered every 4 weeks in RA and PJIA and every 8 weeks in SJIA as a single intravenous drip infusion over 1 hour.

The European Commission approved its first tocilizumab biosimilar, Tyenne (Fresenius Kabi), earlier in 2023 in both subcutaneous and intravenous formulations. Biogen did not comment on whether the company is working on a subcutaneous formulation for tocilizumab-bavi.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved the biosimilar tocilizumab-bavi (Tofidence), Biogen, the drug’s manufacturer, announced on Sept. 29.

It is the first tocilizumab biosimilar approved by the FDA. The reference product, Actemra (Genentech), was first approved by the agency in 2010.

“The approval of Tofidence in the U.S. marks another positive step toward helping more people with chronic autoimmune conditions gain access to leading therapies,” Ian Henshaw, global head of biosimilars at Biogen, said in a statement. “With the increasing numbers of approved biosimilars, we expect increased savings and sustainability for health care systems and an increase in physician choice and patient access to biologics.”

Biogen’s pricing for tocilizumab-bavi will be available closer to the product’s launch date, which has yet to be determined, a company spokesman said. The U.S. average monthly cost of Actemra for rheumatoid arthritis, administered intravenously, is $2,134-$4,268 depending on dosage, according to a Genentech spokesperson.

Tocilizumab-bavi is an intravenous formulation (20 mg/mL) indicated for treatment of moderately to severely active RA, polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). The medication is administered every 4 weeks in RA and PJIA and every 8 weeks in SJIA as a single intravenous drip infusion over 1 hour.

The European Commission approved its first tocilizumab biosimilar, Tyenne (Fresenius Kabi), earlier in 2023 in both subcutaneous and intravenous formulations. Biogen did not comment on whether the company is working on a subcutaneous formulation for tocilizumab-bavi.

A version of this article appeared on Medscape.com.

The question looms large for patients with stable systemic lupus erythematosus (SLE): to taper or not to taper corticosteroids or immunosuppressive therapy? For patients and the physicians treating them, the evidence points in both directions. Flares are exacerbated by tapering, but simultaneously organ damage is tempered. Where is the balance? What competing factors together inform decision-making?

A recent multinational, observational cohort study conducted by Jiacai Cho, MBBS, of National University Hospital, Singapore, and colleagues, and published in The Lancet Rheumatology concluded that, given the odds of excess flares associated with tapering of corticosteroids and immunosuppressive therapy in patients with stable SLE, drug tapering warrants careful consideration of risks and benefits and is best reserved for those in complete clinical and serological remission with stable disease for at least 6 months. However, in an accompanying editorial, Yann Nguyen, MD, MPH, and Nathalie Costedoat-Chalumeau, MD, PhD, of the National Referral Center for Rare Autoimmune and Systemic Diseases at Cochin Hospital, Paris, and the Center for Research in Epidemiology and Statistics at Paris City University, argued for tipping the scale back from some of those expressed cautions.

Bruce Jancin/MDedge News

In interviews, experts in the field expressed both strong appreciation for the cohort study and, like the editorialists, cognizance of its limitations.

Dr. Cho and colleagues recruited 3,002 adult patients with SLE (92.2% female, median age 39.5 years), from 25 sites across 13 Asia-Pacific countries. They were receiving routine clinical care and had achieved stable disease in at least one of two or more visits. Stable disease was defined by meeting criteria for Lupus Low Disease Activity State (LLDAS; SLE Disease Activity Index 2000 [SLEDAI-2K] score ≤ 4, Physician Global Assessment [PGA] ≤ 1, and prednisolone ≤ 7.5 mg/day), the 2021 DORIS definition of remission (clinical SLEDAI-2K score 0, PGA score < 0.5, and prednisolone dose ≤ 5 mg/day), or DORIS complete remission on therapy (SLEDAI-2K score 0, PGA score < 0.5, and prednisolone dose ≤ 5 mg/day). Any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate) defined tapering. The investigators compared the odds of disease flares (SELENA-SLEDAI Flare Index) at the visit following tapering among those with tapering versus those who had continued the same drug doses.
 

Higher odds of flare with tapering

Tapering, compared with continuing with the same dose, was clearly associated with higher odds of flare at the next visit (11.4% with continuing vs. 17.0% with tapering; odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P = .0005). Flares among patients who tapered were also slightly more often severe than with continuing the same dose (21.5% of flares vs. 19.7%). The level of remission at the time of tapering also mattered. Of 2,095 continuous tapering attempts, 860 (41.1%) were initiated in LLDAS, 596 (28.4%) in remission, and 639 (30.5%) in complete remission. Tapering when in LLDAS or remission, compared with complete remission, was associated with a higher likelihood of flare by 1 year (LLDAS: OR, 1.37; 95% CI, 1.03-1.81; P = .029; and remission: OR, 1.45; 95% CI, 1.08-1.94; P = .013). Time to first flare followed the same pattern. Also, sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit and flares in 1 year, and longer time to flare.

Take baseline disease status, hydroxychloroquine’s effect into account

Dr. Nguyen and Dr. Costedoat-Chalumeau underscored several factors that may soften the risk for flares seen with tapering. They pointed to higher baseline doses of prednisone and immunosuppressants (and thus likely more severe disease that is more likely to flare) in the patients with tapering. Also, the SELENA-SLEDAI Flare Index used in the study classifies some clinically insignificant flares as mild to moderate and ignores the benefit of tapering. (It classifies patients as having a severe flare even when starting a new immunosuppressant prescription, such as azathioprine, methotrexate, or both, in an effort to reduce corticosteroid use.) They wrote that the study did not assess the rate of clinically meaningful flares (“essentially renal flares”), nor did it highlight that the “tiny” increase in absolute risk of severe flares (from 2.2% to 3.7%) could be further contextualized by the offset of the smaller, unmeasured rate of clinically significant flares and the “extremely relevant” risk of concomitant damage from prolonged treatment.

Dr. Nguyen and Dr. Costedoat-Chalumeau urged hydroxychloroquine use for all patients unless clearly contraindicated. In their own research, they have detailed hydroxychloroquine benefits in reducing not only flare risk, but also comorbidities, damage, and mortality. In the current study, the prevalence of hydroxychloroquine use in all the patient visits was only 63.3%. “We can assume that if more patients had been treated with hydroxychloroquine, both the number of flares and the difference between the two strategies would have been lower,” they wrote. They cited findings from a study of patients in remission for 2 years or longer in the Toronto Lupus Cohort in which a gradual taper of corticosteroids over 1 year was safe and feasible and resulted in less damage accrual at 24 months than not tapering. Optimizing tapering can minimize flare risk, they concluded.

McGill University Health Center

Tapering SLE medications always involves some chance of flare and has to be considered a calculated risk, Sasha Bernatsky, MD, the James McGill professor of medicine in the division of rheumatology at McGill University, Montreal, said in an interview. “Long-term prednisone is not good for patients. I have heard it called ‘the miracle drug from hell’ – meaning that, yes, it controls disease, but at a cost of long-term complications. So we must be conscientious about tapering prednisone.” She observed that in the short-term, there may not be a huge risk to keeping a patient on an antimalarial and counseling patients to stay on it because their risk of flare is higher if they taper. Rheumatologists usually agree, however, that after 10 years or more, there is a real chance of retinal toxicity. “In our Montreal cohort, the risk of retinal toxicity was 5% after an average of 12.8 years of antimalarial use. My concern is that if a patient develops SLE in their 20s, how do we decide if we should keep them on an antimalarial for the next 60 or 70 years? If we keep them on the drug from age 25 to 45, and they then get retinal toxicity, they would essentially never be able to be on the drug again. So I do try to keep patients on the lowest dose of an antimalarial that is possible.”

Dr. Bernatsky pointed out further, “We think about tapering other immunosuppressants (such as methotrexate or mycophenolate or azathioprine) quite differently than prednisone tapering. We take our time a bit more, since many patients will tolerate being on standard doses of these drugs fairly well. If or when we do consider tapering these drugs, both our intuition and the literature suggests that someone with worse baseline disease activity or severity, who has needed a lot of steroids and multiple combinations of drugs to control disease, has a higher chance of flaring than someone with milder disease. As the editorial points out, lupus physicians (and their patients) need to think carefully about the patient’s risk profile, and be sure to tailor follow-up based on flare risk.”

Frank discussions with patients about the risks of tapering are needed, she said. “On one hand, there is consensus about how some aspects of lupus should be managed (for example, aggressive treatment of severe nephritis), but on the other hand, when it comes to long-term management and especially discussing tapering, we must have good discussions with patients. When a patient asks if they can taper a drug – many just lower or stop their drugs without asking – I am as honest as I can be, but ultimately have to admit any taper could be associated with a flare. It’s helpful to have actual figures to discuss with patients.”
 

No surprises

“This is an interesting study, which did not produce any surprises,” Dafna D. Gladman, MD, professor of medicine at University of Toronto and senior scientist at the university’s Schroeder Arthritis Institute, said when asked to comment. “We already knew from previous studies that abrupt withdrawal is not a good idea, and that if you taper when a patient is under conditions of remission, the rate of flare is actually lower than the usual rate of flare that occurs in people who continue on these medications. But the major limitation is that they did not specifically look at those who we would taper in clinical practice. In addition, they do not specify that the patients had to be on low-dose glucocorticoids before tapering, and they combined both immunosuppressive and steroids. It is not clear from the study what the excess flare rate was, or whether the flares were mild or severe. Most flares in patients with SLE are mild, consisting of skin and joint manifestations, while only a few patients have flares in kidney or neurologic manifestations.”

Dr. Gladman described her approach to tapering: “We aim for our patients to be taking no more than 5 mg of prednisone and to be in at least clinical remission with a SLEDAI-2K of 0 for at least 2 years before we would taper to glucocorticoids withdrawal. We always withdraw glucocorticoids first and immunosuppressives later, and keep patients on antimalarials the longest, unless there are specific side effects to the immunosuppressive or antimalarials which require their cessation earlier.”
 

Uncertainty persists

Other SLE experts weighing in confirmed the view that future research should aim to achieve clarity about the relative risks and benefits of tapering SLE drug regimens to maintain disease remission while minimizing potential for organ damage.

Oklahoma Medical Research Foundation

“Steroids are our friend and our enemy,” Joan T. Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said in an interview. “If a person with lupus is in a lot of trouble, corticosteroids are almost universally a good option to get them out. But for too many decades, for too many patients, despite all the improvements we have made in better understanding the disease and developing some promising new treatments, we have yet to shed the inexorable toxicity in multiple organs of steroid dependence.” She continued, “Corticosteroids, even at low dose, may have broad-spectrum effects. But, in fact, so do many of the more ‘targeted’ agents. If all patients were lined up at the beginning of a study while being given azathioprine or a calcineurin inhibitor or belimumab at a stable, tolerable dose, you might see the same data if you tapered that agent down. What we really need is improved individualized guidance about when and how fast to remove immune modulators from stable patients with lupus without disturbing the balance that had been achieved in such a quiescent patient.”

Cedars-Sinai Medical Center

That enduring uncertainty was echoed by Daniel J. Wallace, MD, professor of medicine at Cedars-Sinai Medical Center, Los Angeles: “The take-home message from this interesting paper,” he commented, “is that current lupus biomarkers are not adequate. They do not guide the practitioner well enough, so that all too often medication regimens are tapered even though the risks are not really well known. Also, there is evidence in the literature that fibrosis and ‘damage’ progress even if acute phase reactants such as sedimentation rate, [C-reactive protein], complement 3 and 4, and anti-dsDNA are normal. We don’t have a good metric to detect them.”

Dr. Cho and colleagues’ study was funded by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Serono, GlaxoSmithKline, and UCB. Dr. Gladman disclosed consulting and/or research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

The question looms large for patients with stable systemic lupus erythematosus (SLE): to taper or not to taper corticosteroids or immunosuppressive therapy? For patients and the physicians treating them, the evidence points in both directions. Flares are exacerbated by tapering, but simultaneously organ damage is tempered. Where is the balance? What competing factors together inform decision-making?

A recent multinational, observational cohort study conducted by Jiacai Cho, MBBS, of National University Hospital, Singapore, and colleagues, and published in The Lancet Rheumatology concluded that, given the odds of excess flares associated with tapering of corticosteroids and immunosuppressive therapy in patients with stable SLE, drug tapering warrants careful consideration of risks and benefits and is best reserved for those in complete clinical and serological remission with stable disease for at least 6 months. However, in an accompanying editorial, Yann Nguyen, MD, MPH, and Nathalie Costedoat-Chalumeau, MD, PhD, of the National Referral Center for Rare Autoimmune and Systemic Diseases at Cochin Hospital, Paris, and the Center for Research in Epidemiology and Statistics at Paris City University, argued for tipping the scale back from some of those expressed cautions.

Bruce Jancin/MDedge News

In interviews, experts in the field expressed both strong appreciation for the cohort study and, like the editorialists, cognizance of its limitations.

Dr. Cho and colleagues recruited 3,002 adult patients with SLE (92.2% female, median age 39.5 years), from 25 sites across 13 Asia-Pacific countries. They were receiving routine clinical care and had achieved stable disease in at least one of two or more visits. Stable disease was defined by meeting criteria for Lupus Low Disease Activity State (LLDAS; SLE Disease Activity Index 2000 [SLEDAI-2K] score ≤ 4, Physician Global Assessment [PGA] ≤ 1, and prednisolone ≤ 7.5 mg/day), the 2021 DORIS definition of remission (clinical SLEDAI-2K score 0, PGA score < 0.5, and prednisolone dose ≤ 5 mg/day), or DORIS complete remission on therapy (SLEDAI-2K score 0, PGA score < 0.5, and prednisolone dose ≤ 5 mg/day). Any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate) defined tapering. The investigators compared the odds of disease flares (SELENA-SLEDAI Flare Index) at the visit following tapering among those with tapering versus those who had continued the same drug doses.
 

Higher odds of flare with tapering

Tapering, compared with continuing with the same dose, was clearly associated with higher odds of flare at the next visit (11.4% with continuing vs. 17.0% with tapering; odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P = .0005). Flares among patients who tapered were also slightly more often severe than with continuing the same dose (21.5% of flares vs. 19.7%). The level of remission at the time of tapering also mattered. Of 2,095 continuous tapering attempts, 860 (41.1%) were initiated in LLDAS, 596 (28.4%) in remission, and 639 (30.5%) in complete remission. Tapering when in LLDAS or remission, compared with complete remission, was associated with a higher likelihood of flare by 1 year (LLDAS: OR, 1.37; 95% CI, 1.03-1.81; P = .029; and remission: OR, 1.45; 95% CI, 1.08-1.94; P = .013). Time to first flare followed the same pattern. Also, sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit and flares in 1 year, and longer time to flare.

Take baseline disease status, hydroxychloroquine’s effect into account

Dr. Nguyen and Dr. Costedoat-Chalumeau underscored several factors that may soften the risk for flares seen with tapering. They pointed to higher baseline doses of prednisone and immunosuppressants (and thus likely more severe disease that is more likely to flare) in the patients with tapering. Also, the SELENA-SLEDAI Flare Index used in the study classifies some clinically insignificant flares as mild to moderate and ignores the benefit of tapering. (It classifies patients as having a severe flare even when starting a new immunosuppressant prescription, such as azathioprine, methotrexate, or both, in an effort to reduce corticosteroid use.) They wrote that the study did not assess the rate of clinically meaningful flares (“essentially renal flares”), nor did it highlight that the “tiny” increase in absolute risk of severe flares (from 2.2% to 3.7%) could be further contextualized by the offset of the smaller, unmeasured rate of clinically significant flares and the “extremely relevant” risk of concomitant damage from prolonged treatment.

Dr. Nguyen and Dr. Costedoat-Chalumeau urged hydroxychloroquine use for all patients unless clearly contraindicated. In their own research, they have detailed hydroxychloroquine benefits in reducing not only flare risk, but also comorbidities, damage, and mortality. In the current study, the prevalence of hydroxychloroquine use in all the patient visits was only 63.3%. “We can assume that if more patients had been treated with hydroxychloroquine, both the number of flares and the difference between the two strategies would have been lower,” they wrote. They cited findings from a study of patients in remission for 2 years or longer in the Toronto Lupus Cohort in which a gradual taper of corticosteroids over 1 year was safe and feasible and resulted in less damage accrual at 24 months than not tapering. Optimizing tapering can minimize flare risk, they concluded.

McGill University Health Center

Tapering SLE medications always involves some chance of flare and has to be considered a calculated risk, Sasha Bernatsky, MD, the James McGill professor of medicine in the division of rheumatology at McGill University, Montreal, said in an interview. “Long-term prednisone is not good for patients. I have heard it called ‘the miracle drug from hell’ – meaning that, yes, it controls disease, but at a cost of long-term complications. So we must be conscientious about tapering prednisone.” She observed that in the short-term, there may not be a huge risk to keeping a patient on an antimalarial and counseling patients to stay on it because their risk of flare is higher if they taper. Rheumatologists usually agree, however, that after 10 years or more, there is a real chance of retinal toxicity. “In our Montreal cohort, the risk of retinal toxicity was 5% after an average of 12.8 years of antimalarial use. My concern is that if a patient develops SLE in their 20s, how do we decide if we should keep them on an antimalarial for the next 60 or 70 years? If we keep them on the drug from age 25 to 45, and they then get retinal toxicity, they would essentially never be able to be on the drug again. So I do try to keep patients on the lowest dose of an antimalarial that is possible.”

Dr. Bernatsky pointed out further, “We think about tapering other immunosuppressants (such as methotrexate or mycophenolate or azathioprine) quite differently than prednisone tapering. We take our time a bit more, since many patients will tolerate being on standard doses of these drugs fairly well. If or when we do consider tapering these drugs, both our intuition and the literature suggests that someone with worse baseline disease activity or severity, who has needed a lot of steroids and multiple combinations of drugs to control disease, has a higher chance of flaring than someone with milder disease. As the editorial points out, lupus physicians (and their patients) need to think carefully about the patient’s risk profile, and be sure to tailor follow-up based on flare risk.”

Frank discussions with patients about the risks of tapering are needed, she said. “On one hand, there is consensus about how some aspects of lupus should be managed (for example, aggressive treatment of severe nephritis), but on the other hand, when it comes to long-term management and especially discussing tapering, we must have good discussions with patients. When a patient asks if they can taper a drug – many just lower or stop their drugs without asking – I am as honest as I can be, but ultimately have to admit any taper could be associated with a flare. It’s helpful to have actual figures to discuss with patients.”
 

No surprises

“This is an interesting study, which did not produce any surprises,” Dafna D. Gladman, MD, professor of medicine at University of Toronto and senior scientist at the university’s Schroeder Arthritis Institute, said when asked to comment. “We already knew from previous studies that abrupt withdrawal is not a good idea, and that if you taper when a patient is under conditions of remission, the rate of flare is actually lower than the usual rate of flare that occurs in people who continue on these medications. But the major limitation is that they did not specifically look at those who we would taper in clinical practice. In addition, they do not specify that the patients had to be on low-dose glucocorticoids before tapering, and they combined both immunosuppressive and steroids. It is not clear from the study what the excess flare rate was, or whether the flares were mild or severe. Most flares in patients with SLE are mild, consisting of skin and joint manifestations, while only a few patients have flares in kidney or neurologic manifestations.”

Dr. Gladman described her approach to tapering: “We aim for our patients to be taking no more than 5 mg of prednisone and to be in at least clinical remission with a SLEDAI-2K of 0 for at least 2 years before we would taper to glucocorticoids withdrawal. We always withdraw glucocorticoids first and immunosuppressives later, and keep patients on antimalarials the longest, unless there are specific side effects to the immunosuppressive or antimalarials which require their cessation earlier.”
 

Uncertainty persists

Other SLE experts weighing in confirmed the view that future research should aim to achieve clarity about the relative risks and benefits of tapering SLE drug regimens to maintain disease remission while minimizing potential for organ damage.

Oklahoma Medical Research Foundation

“Steroids are our friend and our enemy,” Joan T. Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said in an interview. “If a person with lupus is in a lot of trouble, corticosteroids are almost universally a good option to get them out. But for too many decades, for too many patients, despite all the improvements we have made in better understanding the disease and developing some promising new treatments, we have yet to shed the inexorable toxicity in multiple organs of steroid dependence.” She continued, “Corticosteroids, even at low dose, may have broad-spectrum effects. But, in fact, so do many of the more ‘targeted’ agents. If all patients were lined up at the beginning of a study while being given azathioprine or a calcineurin inhibitor or belimumab at a stable, tolerable dose, you might see the same data if you tapered that agent down. What we really need is improved individualized guidance about when and how fast to remove immune modulators from stable patients with lupus without disturbing the balance that had been achieved in such a quiescent patient.”

Cedars-Sinai Medical Center

That enduring uncertainty was echoed by Daniel J. Wallace, MD, professor of medicine at Cedars-Sinai Medical Center, Los Angeles: “The take-home message from this interesting paper,” he commented, “is that current lupus biomarkers are not adequate. They do not guide the practitioner well enough, so that all too often medication regimens are tapered even though the risks are not really well known. Also, there is evidence in the literature that fibrosis and ‘damage’ progress even if acute phase reactants such as sedimentation rate, [C-reactive protein], complement 3 and 4, and anti-dsDNA are normal. We don’t have a good metric to detect them.”

Dr. Cho and colleagues’ study was funded by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Serono, GlaxoSmithKline, and UCB. Dr. Gladman disclosed consulting and/or research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

The question looms large for patients with stable systemic lupus erythematosus (SLE): to taper or not to taper corticosteroids or immunosuppressive therapy? For patients and the physicians treating them, the evidence points in both directions. Flares are exacerbated by tapering, but simultaneously organ damage is tempered. Where is the balance? What competing factors together inform decision-making?

A recent multinational, observational cohort study conducted by Jiacai Cho, MBBS, of National University Hospital, Singapore, and colleagues, and published in The Lancet Rheumatology concluded that, given the odds of excess flares associated with tapering of corticosteroids and immunosuppressive therapy in patients with stable SLE, drug tapering warrants careful consideration of risks and benefits and is best reserved for those in complete clinical and serological remission with stable disease for at least 6 months. However, in an accompanying editorial, Yann Nguyen, MD, MPH, and Nathalie Costedoat-Chalumeau, MD, PhD, of the National Referral Center for Rare Autoimmune and Systemic Diseases at Cochin Hospital, Paris, and the Center for Research in Epidemiology and Statistics at Paris City University, argued for tipping the scale back from some of those expressed cautions.

Bruce Jancin/MDedge News

In interviews, experts in the field expressed both strong appreciation for the cohort study and, like the editorialists, cognizance of its limitations.

Dr. Cho and colleagues recruited 3,002 adult patients with SLE (92.2% female, median age 39.5 years), from 25 sites across 13 Asia-Pacific countries. They were receiving routine clinical care and had achieved stable disease in at least one of two or more visits. Stable disease was defined by meeting criteria for Lupus Low Disease Activity State (LLDAS; SLE Disease Activity Index 2000 [SLEDAI-2K] score ≤ 4, Physician Global Assessment [PGA] ≤ 1, and prednisolone ≤ 7.5 mg/day), the 2021 DORIS definition of remission (clinical SLEDAI-2K score 0, PGA score < 0.5, and prednisolone dose ≤ 5 mg/day), or DORIS complete remission on therapy (SLEDAI-2K score 0, PGA score < 0.5, and prednisolone dose ≤ 5 mg/day). Any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate) defined tapering. The investigators compared the odds of disease flares (SELENA-SLEDAI Flare Index) at the visit following tapering among those with tapering versus those who had continued the same drug doses.
 

Higher odds of flare with tapering

Tapering, compared with continuing with the same dose, was clearly associated with higher odds of flare at the next visit (11.4% with continuing vs. 17.0% with tapering; odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P = .0005). Flares among patients who tapered were also slightly more often severe than with continuing the same dose (21.5% of flares vs. 19.7%). The level of remission at the time of tapering also mattered. Of 2,095 continuous tapering attempts, 860 (41.1%) were initiated in LLDAS, 596 (28.4%) in remission, and 639 (30.5%) in complete remission. Tapering when in LLDAS or remission, compared with complete remission, was associated with a higher likelihood of flare by 1 year (LLDAS: OR, 1.37; 95% CI, 1.03-1.81; P = .029; and remission: OR, 1.45; 95% CI, 1.08-1.94; P = .013). Time to first flare followed the same pattern. Also, sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit and flares in 1 year, and longer time to flare.

Take baseline disease status, hydroxychloroquine’s effect into account

Dr. Nguyen and Dr. Costedoat-Chalumeau underscored several factors that may soften the risk for flares seen with tapering. They pointed to higher baseline doses of prednisone and immunosuppressants (and thus likely more severe disease that is more likely to flare) in the patients with tapering. Also, the SELENA-SLEDAI Flare Index used in the study classifies some clinically insignificant flares as mild to moderate and ignores the benefit of tapering. (It classifies patients as having a severe flare even when starting a new immunosuppressant prescription, such as azathioprine, methotrexate, or both, in an effort to reduce corticosteroid use.) They wrote that the study did not assess the rate of clinically meaningful flares (“essentially renal flares”), nor did it highlight that the “tiny” increase in absolute risk of severe flares (from 2.2% to 3.7%) could be further contextualized by the offset of the smaller, unmeasured rate of clinically significant flares and the “extremely relevant” risk of concomitant damage from prolonged treatment.

Dr. Nguyen and Dr. Costedoat-Chalumeau urged hydroxychloroquine use for all patients unless clearly contraindicated. In their own research, they have detailed hydroxychloroquine benefits in reducing not only flare risk, but also comorbidities, damage, and mortality. In the current study, the prevalence of hydroxychloroquine use in all the patient visits was only 63.3%. “We can assume that if more patients had been treated with hydroxychloroquine, both the number of flares and the difference between the two strategies would have been lower,” they wrote. They cited findings from a study of patients in remission for 2 years or longer in the Toronto Lupus Cohort in which a gradual taper of corticosteroids over 1 year was safe and feasible and resulted in less damage accrual at 24 months than not tapering. Optimizing tapering can minimize flare risk, they concluded.

McGill University Health Center

Tapering SLE medications always involves some chance of flare and has to be considered a calculated risk, Sasha Bernatsky, MD, the James McGill professor of medicine in the division of rheumatology at McGill University, Montreal, said in an interview. “Long-term prednisone is not good for patients. I have heard it called ‘the miracle drug from hell’ – meaning that, yes, it controls disease, but at a cost of long-term complications. So we must be conscientious about tapering prednisone.” She observed that in the short-term, there may not be a huge risk to keeping a patient on an antimalarial and counseling patients to stay on it because their risk of flare is higher if they taper. Rheumatologists usually agree, however, that after 10 years or more, there is a real chance of retinal toxicity. “In our Montreal cohort, the risk of retinal toxicity was 5% after an average of 12.8 years of antimalarial use. My concern is that if a patient develops SLE in their 20s, how do we decide if we should keep them on an antimalarial for the next 60 or 70 years? If we keep them on the drug from age 25 to 45, and they then get retinal toxicity, they would essentially never be able to be on the drug again. So I do try to keep patients on the lowest dose of an antimalarial that is possible.”

Dr. Bernatsky pointed out further, “We think about tapering other immunosuppressants (such as methotrexate or mycophenolate or azathioprine) quite differently than prednisone tapering. We take our time a bit more, since many patients will tolerate being on standard doses of these drugs fairly well. If or when we do consider tapering these drugs, both our intuition and the literature suggests that someone with worse baseline disease activity or severity, who has needed a lot of steroids and multiple combinations of drugs to control disease, has a higher chance of flaring than someone with milder disease. As the editorial points out, lupus physicians (and their patients) need to think carefully about the patient’s risk profile, and be sure to tailor follow-up based on flare risk.”

Frank discussions with patients about the risks of tapering are needed, she said. “On one hand, there is consensus about how some aspects of lupus should be managed (for example, aggressive treatment of severe nephritis), but on the other hand, when it comes to long-term management and especially discussing tapering, we must have good discussions with patients. When a patient asks if they can taper a drug – many just lower or stop their drugs without asking – I am as honest as I can be, but ultimately have to admit any taper could be associated with a flare. It’s helpful to have actual figures to discuss with patients.”
 

No surprises

“This is an interesting study, which did not produce any surprises,” Dafna D. Gladman, MD, professor of medicine at University of Toronto and senior scientist at the university’s Schroeder Arthritis Institute, said when asked to comment. “We already knew from previous studies that abrupt withdrawal is not a good idea, and that if you taper when a patient is under conditions of remission, the rate of flare is actually lower than the usual rate of flare that occurs in people who continue on these medications. But the major limitation is that they did not specifically look at those who we would taper in clinical practice. In addition, they do not specify that the patients had to be on low-dose glucocorticoids before tapering, and they combined both immunosuppressive and steroids. It is not clear from the study what the excess flare rate was, or whether the flares were mild or severe. Most flares in patients with SLE are mild, consisting of skin and joint manifestations, while only a few patients have flares in kidney or neurologic manifestations.”

Dr. Gladman described her approach to tapering: “We aim for our patients to be taking no more than 5 mg of prednisone and to be in at least clinical remission with a SLEDAI-2K of 0 for at least 2 years before we would taper to glucocorticoids withdrawal. We always withdraw glucocorticoids first and immunosuppressives later, and keep patients on antimalarials the longest, unless there are specific side effects to the immunosuppressive or antimalarials which require their cessation earlier.”
 

Uncertainty persists

Other SLE experts weighing in confirmed the view that future research should aim to achieve clarity about the relative risks and benefits of tapering SLE drug regimens to maintain disease remission while minimizing potential for organ damage.

Oklahoma Medical Research Foundation

“Steroids are our friend and our enemy,” Joan T. Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said in an interview. “If a person with lupus is in a lot of trouble, corticosteroids are almost universally a good option to get them out. But for too many decades, for too many patients, despite all the improvements we have made in better understanding the disease and developing some promising new treatments, we have yet to shed the inexorable toxicity in multiple organs of steroid dependence.” She continued, “Corticosteroids, even at low dose, may have broad-spectrum effects. But, in fact, so do many of the more ‘targeted’ agents. If all patients were lined up at the beginning of a study while being given azathioprine or a calcineurin inhibitor or belimumab at a stable, tolerable dose, you might see the same data if you tapered that agent down. What we really need is improved individualized guidance about when and how fast to remove immune modulators from stable patients with lupus without disturbing the balance that had been achieved in such a quiescent patient.”

Cedars-Sinai Medical Center

That enduring uncertainty was echoed by Daniel J. Wallace, MD, professor of medicine at Cedars-Sinai Medical Center, Los Angeles: “The take-home message from this interesting paper,” he commented, “is that current lupus biomarkers are not adequate. They do not guide the practitioner well enough, so that all too often medication regimens are tapered even though the risks are not really well known. Also, there is evidence in the literature that fibrosis and ‘damage’ progress even if acute phase reactants such as sedimentation rate, [C-reactive protein], complement 3 and 4, and anti-dsDNA are normal. We don’t have a good metric to detect them.”

Dr. Cho and colleagues’ study was funded by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Serono, GlaxoSmithKline, and UCB. Dr. Gladman disclosed consulting and/or research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.