Rheumatology

Lower limits on serum urate levels applied in gout management may be based on a misreading of data on mortality risks, researchers say.

Low urate levels may not in themselves pose a risk of death but may be a sign of some other illness, said Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania in Philadelphia.

jarun011/Thinkstock

“It points us towards being more reassured that we can be aggressive in treating gout without a concern about long-term effects for our patients,” he said in an interview. He and colleagues published their findings online in Arthritis & Rheumatology.

Previous research has linked high levels of urate with excessive fat and low levels of urate with loss of skeletal muscle mass. And epidemiologic studies have shown a U-shaped relationship between urate levels and mortality, suggesting that very high and very low levels of urate could be harmful.

Based on this correlation, and the theory that urate could have antioxidant benefits, some professional societies have recommended not lowering urate levels below a defined threshold when treating gout. The European Alliance of Associations for Rheumatology has recommended a lower limit of 3 mg/dL.

But the evidence doesn’t entirely support this caution. For example, in a clinical trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose mean serum urate dropped below 2 mg/dL did not die in higher proportions than patients with higher urate levels.

To better understand the risk of low urate, Dr. Baker and colleagues analyzed data on 13,979 participants in the National Health and Nutrition Examination Survey (NHANES) during 1999-2006. The dataset included whole-body dual-energy x-ray absorptiometry (DXA) body composition measures as well as urate levels.

The researchers argue this measurement reveals more about a person’s overall health than body mass index (BMI), which doesn’t distinguish between mass from fat and mass from muscle.

They defined low lean body mass, or sarcopenia, as an appendicular lean mass index relative to fat mass index z score of –1. And they defined low urate as less than 2.5 mg/dL in women and less than 3.5 mg/dL in men.

They found that 29% of people with low urate had low lean body mass, compared with 16% of people with normal urate levels. The difference was statistically significant (P = .001).

They found an association between low urate and increased mortality (hazard ratio, 1.61; 95% confidence interval, 1.14-2.28; P = .008). But that association lost its statistical significance when the researchers adjusted for body composition and weight loss (HR, 1.30; 95% CI, 0.92-1.85; P = .13).

Dr. Baker thinks the association between elevated mortality and low urate can be explained by conditions such as cancer or lung inflammation that might on one hand increase the risk of death and on the other hand lower urate levels by lowering muscle mass. “Low uric acid levels are observed in people who have lost weight for unhealthy reasons, and that can explain relationships with long-term outcomes,” he said.

Proportions of muscle and fat could not account for the risk of mortality associated with high levels of urate, the researchers found. Those participants with urate levels above 5.7 mg/dL had a higher risk of death with higher levels of urate, and this persisted even after statistical adjustment for body composition.

The study sheds light on an important area of controversy, said Mehdi Fini, MD, of the department of medicine at the University of Colorado at Denver, Aurora, who was not involved in the research.

But body composition does not entirely explain the relationship between urate and mortality, he told this news organization. Medications used to lower urate can cause side effects that might increase mortality, he said.

Also, he said, it’s important to understand the role of comorbidities. He cited evidence that low urate is associated with renal, cardiovascular, and pulmonary conditions. Safe levels of urate might differ depending on these factors. So rather than applying the same target serum level to all patients, perhaps researchers should investigate whether lowering urate by a percentage of the patient’s current level is safer and more effective, he suggested.

He agreed with an editorial that also appeared in Arthritis & Rheumatology saying that there is no evidence for a benefit in lowering urate much below 5 mg/dL. “No matter what, I think we should just be careful,” Dr. Fini said.

Dr. Fini and Dr. Baker report no relevant financial relationships. Dr. Baker acknowledged support from a VA Clinical Science Research & Development Merit Award and a Rehabilitation R&D Merit Award.

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

Lower limits on serum urate levels applied in gout management may be based on a misreading of data on mortality risks, researchers say.

Low urate levels may not in themselves pose a risk of death but may be a sign of some other illness, said Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania in Philadelphia.

jarun011/Thinkstock

“It points us towards being more reassured that we can be aggressive in treating gout without a concern about long-term effects for our patients,” he said in an interview. He and colleagues published their findings online in Arthritis & Rheumatology.

Previous research has linked high levels of urate with excessive fat and low levels of urate with loss of skeletal muscle mass. And epidemiologic studies have shown a U-shaped relationship between urate levels and mortality, suggesting that very high and very low levels of urate could be harmful.

Based on this correlation, and the theory that urate could have antioxidant benefits, some professional societies have recommended not lowering urate levels below a defined threshold when treating gout. The European Alliance of Associations for Rheumatology has recommended a lower limit of 3 mg/dL.

But the evidence doesn’t entirely support this caution. For example, in a clinical trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose mean serum urate dropped below 2 mg/dL did not die in higher proportions than patients with higher urate levels.

To better understand the risk of low urate, Dr. Baker and colleagues analyzed data on 13,979 participants in the National Health and Nutrition Examination Survey (NHANES) during 1999-2006. The dataset included whole-body dual-energy x-ray absorptiometry (DXA) body composition measures as well as urate levels.

The researchers argue this measurement reveals more about a person’s overall health than body mass index (BMI), which doesn’t distinguish between mass from fat and mass from muscle.

They defined low lean body mass, or sarcopenia, as an appendicular lean mass index relative to fat mass index z score of –1. And they defined low urate as less than 2.5 mg/dL in women and less than 3.5 mg/dL in men.

They found that 29% of people with low urate had low lean body mass, compared with 16% of people with normal urate levels. The difference was statistically significant (P = .001).

They found an association between low urate and increased mortality (hazard ratio, 1.61; 95% confidence interval, 1.14-2.28; P = .008). But that association lost its statistical significance when the researchers adjusted for body composition and weight loss (HR, 1.30; 95% CI, 0.92-1.85; P = .13).

Dr. Baker thinks the association between elevated mortality and low urate can be explained by conditions such as cancer or lung inflammation that might on one hand increase the risk of death and on the other hand lower urate levels by lowering muscle mass. “Low uric acid levels are observed in people who have lost weight for unhealthy reasons, and that can explain relationships with long-term outcomes,” he said.

Proportions of muscle and fat could not account for the risk of mortality associated with high levels of urate, the researchers found. Those participants with urate levels above 5.7 mg/dL had a higher risk of death with higher levels of urate, and this persisted even after statistical adjustment for body composition.

The study sheds light on an important area of controversy, said Mehdi Fini, MD, of the department of medicine at the University of Colorado at Denver, Aurora, who was not involved in the research.

But body composition does not entirely explain the relationship between urate and mortality, he told this news organization. Medications used to lower urate can cause side effects that might increase mortality, he said.

Also, he said, it’s important to understand the role of comorbidities. He cited evidence that low urate is associated with renal, cardiovascular, and pulmonary conditions. Safe levels of urate might differ depending on these factors. So rather than applying the same target serum level to all patients, perhaps researchers should investigate whether lowering urate by a percentage of the patient’s current level is safer and more effective, he suggested.

He agreed with an editorial that also appeared in Arthritis & Rheumatology saying that there is no evidence for a benefit in lowering urate much below 5 mg/dL. “No matter what, I think we should just be careful,” Dr. Fini said.

Dr. Fini and Dr. Baker report no relevant financial relationships. Dr. Baker acknowledged support from a VA Clinical Science Research & Development Merit Award and a Rehabilitation R&D Merit Award.

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

Lower limits on serum urate levels applied in gout management may be based on a misreading of data on mortality risks, researchers say.

Low urate levels may not in themselves pose a risk of death but may be a sign of some other illness, said Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania in Philadelphia.

jarun011/Thinkstock

“It points us towards being more reassured that we can be aggressive in treating gout without a concern about long-term effects for our patients,” he said in an interview. He and colleagues published their findings online in Arthritis & Rheumatology.

Previous research has linked high levels of urate with excessive fat and low levels of urate with loss of skeletal muscle mass. And epidemiologic studies have shown a U-shaped relationship between urate levels and mortality, suggesting that very high and very low levels of urate could be harmful.

Based on this correlation, and the theory that urate could have antioxidant benefits, some professional societies have recommended not lowering urate levels below a defined threshold when treating gout. The European Alliance of Associations for Rheumatology has recommended a lower limit of 3 mg/dL.

But the evidence doesn’t entirely support this caution. For example, in a clinical trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose mean serum urate dropped below 2 mg/dL did not die in higher proportions than patients with higher urate levels.

To better understand the risk of low urate, Dr. Baker and colleagues analyzed data on 13,979 participants in the National Health and Nutrition Examination Survey (NHANES) during 1999-2006. The dataset included whole-body dual-energy x-ray absorptiometry (DXA) body composition measures as well as urate levels.

The researchers argue this measurement reveals more about a person’s overall health than body mass index (BMI), which doesn’t distinguish between mass from fat and mass from muscle.

They defined low lean body mass, or sarcopenia, as an appendicular lean mass index relative to fat mass index z score of –1. And they defined low urate as less than 2.5 mg/dL in women and less than 3.5 mg/dL in men.

They found that 29% of people with low urate had low lean body mass, compared with 16% of people with normal urate levels. The difference was statistically significant (P = .001).

They found an association between low urate and increased mortality (hazard ratio, 1.61; 95% confidence interval, 1.14-2.28; P = .008). But that association lost its statistical significance when the researchers adjusted for body composition and weight loss (HR, 1.30; 95% CI, 0.92-1.85; P = .13).

Dr. Baker thinks the association between elevated mortality and low urate can be explained by conditions such as cancer or lung inflammation that might on one hand increase the risk of death and on the other hand lower urate levels by lowering muscle mass. “Low uric acid levels are observed in people who have lost weight for unhealthy reasons, and that can explain relationships with long-term outcomes,” he said.

Proportions of muscle and fat could not account for the risk of mortality associated with high levels of urate, the researchers found. Those participants with urate levels above 5.7 mg/dL had a higher risk of death with higher levels of urate, and this persisted even after statistical adjustment for body composition.

The study sheds light on an important area of controversy, said Mehdi Fini, MD, of the department of medicine at the University of Colorado at Denver, Aurora, who was not involved in the research.

But body composition does not entirely explain the relationship between urate and mortality, he told this news organization. Medications used to lower urate can cause side effects that might increase mortality, he said.

Also, he said, it’s important to understand the role of comorbidities. He cited evidence that low urate is associated with renal, cardiovascular, and pulmonary conditions. Safe levels of urate might differ depending on these factors. So rather than applying the same target serum level to all patients, perhaps researchers should investigate whether lowering urate by a percentage of the patient’s current level is safer and more effective, he suggested.

He agreed with an editorial that also appeared in Arthritis & Rheumatology saying that there is no evidence for a benefit in lowering urate much below 5 mg/dL. “No matter what, I think we should just be careful,” Dr. Fini said.

Dr. Fini and Dr. Baker report no relevant financial relationships. Dr. Baker acknowledged support from a VA Clinical Science Research & Development Merit Award and a Rehabilitation R&D Merit Award.

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

Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.

“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.

Bogdanhoda/Thinkstock

“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.

Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.

To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).

Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.

The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.

At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.

Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.

During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.

The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.

Over 12 months, the researchers found:

• Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
• In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
• Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).

Four rheumatologists welcome findings

Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..

“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”

One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”

Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.

“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.

Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.

“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said. 

“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”

Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.

“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.

“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”

Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”

“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.

The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.

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

Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.

“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.

Bogdanhoda/Thinkstock

“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.

Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.

To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).

Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.

The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.

At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.

Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.

During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.

The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.

Over 12 months, the researchers found:

• Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
• In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
• Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).

Four rheumatologists welcome findings

Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..

“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”

One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”

Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.

“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.

Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.

“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said. 

“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”

Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.

“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.

“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”

Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”

“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.

The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.

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

Adding ultrasound (US) to the clinical exam helps predict the likelihood of future gout flares, results of a prospective, observational study conducted in Italy suggest.

“Baseline US findings indicative of MSU [monosodium urate] burden and US-detected inflammation are independent predictors of gout flares over 12 months,” lead author Edoardo Cipolletta, MD, of the rheumatology unit, department of clinical and molecular sciences at Marche Polytechnic University in Ancona, Italy, and colleagues wrote in Rheumatology.

Bogdanhoda/Thinkstock

“We demonstrated that US findings provided an additional value over clinical data in estimating the risk of flares. Moreover, we reported an association between US findings at a joint and the occurrence of gout flares at the same joint,” they added.

Predicting risk of flares and reducing their occurrence are two main challenges in managing gout, the authors wrote. US can be used to scan multiple joints and is widely used in Europe as a low-cost, radiation-free imaging tool that’s easily integrated into clinical practice.

To investigate whether US can predict gout flares, the researchers enrolled 81 consecutive adult patients with gout in the study between April 2019 and March 2021 at one academic rheumatology treatment site in Italy and followed them for 12 months. The authors compared cases (who developed at least one flare within 12 months of the baseline visit) with controls (who self-reported no gout flares over that period).

Patients diagnosed with other inflammatory arthritis and those with coexisting calcium pyrophosphate deposition disease were excluded from the study.

The 71 participants who completed the study were, on average, in their early 60s, and in both groups, all but one were male. At the baseline visit, all had been on stable urate-lowering therapy for at least 6 months and had not had any gout flares in 4 weeks. The mean gout duration was 7 years in the case group and 8 years in controls.

At baseline, all participants underwent physical examination and US of elbows, wrists, second metacarpophalangeal joints, knees, ankles, and first metatarsophalangeal joints by a member of the research team who was blinded to the clinical and laboratory data.

Clinical assessments were scheduled at baseline and at 6-month intervals, and all participants were evaluated by a second researcher who was blinded to US findings.

During follow-up visits, participants were asked to report any gout flare, considered to meet at least three of four criteria: patient-defined flare, pain at rest score higher than 3 on a 0-10 scale, at least one swollen joint, and at least one warm joint. Patients not reaching their target serum urate goal received escalated urate-lowering therapy dosage and anti-inflammatory prophylaxis.

The US indicators of MSU deposits – aggregates, double contour sign, and tophi – were recorded as present or absent. The power Doppler signal was scored from 0 through 4, and summated scores for each US finding were calculated.

Over 12 months, the researchers found:

• Thirty (42.3%) patients had at least one flare, with a median of 2.0 flares. Patients with flares had higher a US median total MSU score (5.0 vs. 2.0; P = .01) and power Doppler signal (3.0 vs. 0; P < .01) than controls.
• In multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the occurrence of flares. The adjusted odds ratio for total MSU score was 1.75 (95% confidence interval, 1.26-2.43) and for power Doppler score was 1.63 (95% CI, 1.12-2.40).
• Also in a multivariate analysis, baseline US scores indicating MSU deposits and US-detected inflammation were significantly linked with the number of flares. The incidence risk ratio for total MSU score adjusted was 1.17 (95% CI, 1.08-1.26) and for power Doppler score was 1.29 (95% CI, 1.19-1.40).

Four rheumatologists welcome findings

Gout remains the most common cause of inflammatory arthritis and a significant reason for hospital visits, noted Narender Annapureddy, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn..

“The study adds to the growing utility of musculoskeletal ultrasound in rheumatology practices to treat various diseases,” he said. “Data that could provide risk prediction for gout flares would be associated with significant benefits in terms of reducing ED visits, hospital admission, and lost work productivity.”

One study limitation, Dr. Annapureddy mentioned, was the single experienced US reader, “which may limit generalizability of results at this time, at least in the United States.”

Yeohan Song, MD, an instructor at Ohio State University Wexner Medical Center, Columbus, integrates US into his practice.

“In gout management, musculoskeletal ultrasound is a useful adjunct to the clinical exam and laboratory markers, particularly [in patients] with recurrent flares despite guideline-directed target serum urate levels,” he said.

Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, pointed out that the US protocol in the study involved imaging knees, ankles, first metatarsophalangeal joints, elbows, wrists, and second metacarpophalangeal joints, and took around 30 minutes to complete.

“That would not be practical in the United States due to time constraints in most rheumatology clinics,” she said. 

“The authors report that a ‘reduced scanning protocol’ of the bilateral knees, ankles, and first metatarsophalangeal joints demonstrated similar predictive ability as the full protocol,” she added, “although scanning six joints still might not be feasible during a typical return patient clinic visit in the United States.”

Philip Chu, MD, clinical associate at Duke University, Durham, N.C., uses diagnostic US to help differentiate borderline gout cases from other arthropathies.

“A baseline scan, a follow-up scan before deciding to stop prophylaxis, or a follow-up scan in the setting of recurrent gout flares despite reaching goal serum uric acid, may be cost-effective time points to perform diagnostic US,” he advised.

“Unfortunately,” he added, “reimbursement for diagnostic US has been decreasing over the years, which makes it challenging to increase diagnostic US to the [frequency of its use] in Europe.”

Asked how most gout care being provided by primary care doctors in the United States affects gout management, Dr. Chu said: “Depending on which guidelines one follows for treating gout – from the American College of Rheumatology or the American College of Physicians – one may be more or less likely to start urate-lowering therapy after the first gout flare.”

“Understanding MSU burden in each patient, or even seeing active inflammation at these sites by increased Doppler signal, may change the threshold for physicians to initiate therapy,” he added.

The study received no funding. Three study authors reported financial involvements with pharmaceutical companies. Dr. Cipolletta, Dr. Annapureddy, Dr. Song, Dr. Tedeschi, and Dr. Chu reported no conflicts of interest.

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

Gout prevalence is more common in Black Americans than White Americans, and the disparity in prevalence is attributable to social determinants of health, according to a recently published article in JAMA Network Open.

“There has been evidence from recent cohort studies in the U.S. that was suggesting that the prevalence and incidence [of gout] was growing among non-White populations,” said Natalie McCormick, PhD, the study’s lead author and postdoctoral research fellow in medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston. “We wanted to do this at the general population level to see how generalizable [that evidence] is.”

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Medical Group, Franklin, Wisc., noted the findings highlight inequities in care for patients with gout that could be improved with greater emphasis on educating patients about their condition.

“I think that what this shows is that in the U.S. ... there still are some disparities in treating gout,” said Dr. Wells, who was not involved with the study. “And that we have ways to mitigate that, with not only aggressive therapy, but also with other tools like counseling patients. At the end of the day, people all want to be educated about the disease.”
 

Greater prevalence disappears with adjustment for socioclinical factors

The cross-sectional analysis involved data from U.S. adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 who self-reported Black or White race.

Investigators considered factors such as excess body mass index (BMI), chronic kidney disease (defined as estimated glomerular filtration rate less than 60 mL/min per 1.73 m²), poverty, poor-quality diet, lower educational level, alcohol consumption, and diuretic use in their analysis.

Dr. McCormick and coinvestigators included a total of 18,693 participants, consisting of 3,304 Black women, 6,195 White women, 3,085 Black men, and 6,109 White men.

They determined that the age-standardized prevalence of gout was 3.5% (95% confidence interval, 2.7%-4.3%) in Black women and 2.0% (95% CI, 1.5% - 2.5%) in White women (age-adjusted odds ratio, 1.81; 95% CI, 1.29-2.53). They calculated that the prevalence was 7.0% (95% CI, 6.2%-7.9%) in Black men and 5.4% (95% CI, 4.7%-6.2%) in White men (age-adjusted OR, 1.26; 95% CI, 1.02-1.55). They found similar differences in the prevalence of hyperuricemia between Black and White Americans.

The increased prevalence of gout in Black Americans, compared with White Americans, does not arise from genetics, according to McCormick. “Our conclusion was that it was due to social determinants of health,” she said. “When we adjusted for all socioclinical risk factors, the racial differences in gout and hyperuricemia prevalence disappeared. Importantly, stepwise regression analysis showed the two biggest drivers of the racial difference in gout prevalence among women were poverty itself, and excess BMI, which can be influenced by poverty.”

Dr. McCormick pointed out that in contrast to the current data, there was no racial difference in the prevalence of gout approximately 2 decades earlier, looking at data from the 1988-1994 NHANES III.

Given the findings, which included the fact that significantly more Black women and men were currently taking diuretics, compared with their White counterparts, Dr. McCormick pointed out clinicians should give more thought to medical therapies prescribed for conditions like high blood pressure to patients with gout or at risk for gout.

“One thing we found was that diuretic use was a driver” of gout, Dr. McCormick said. A prescriber “may want to consider different therapies that present a lower risk of gout if someone has hypertension. There could be greater consideration for prescribing alternatives to diuretics.”

More patient education and rheumatology referrals needed

An impediment to providing that education to patients with gout is unconscious bias on the part of the primary care provider, Dr. Wells said.

“It is about what your perspectives are and what you bring to the table,” he explained. “If you saw [a patient] who looked like someone in your family, that person will be treated differently [than someone who does not look like a family member]. That is where the whole concept [of unconscious bias] comes in.”

Primary care providers need to adopt a holistic approach to gout management that involves counseling about good nutrition, smoking cessation, regular exercise, and limiting alcohol consumption, in addition to medication adherence. Primary care providers may have a bias in treating their Black patients, failing to devote sufficient time and attention to assist them in getting their disease under control, he said.

“Gout should be just like any other chronic disease,” Dr. Wells said. “You need to have a target in mind, and you and your patient need to work together to get to that target. When [patients] end up in rheumatology offices, it is almost too late. I think the take-home message here is that in 2022 ... for any patient who has gout, that patient probably needs to be seen by a rheumatologist because, indeed, with aggressive therapy, preventive therapy, [and] education, and if they are on the right medications, they won’t end up with these crippling joints that we see all the time.”

Dr. McCormick and Dr. Wells disclosed no relevant financial relationships.

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

Gout prevalence is more common in Black Americans than White Americans, and the disparity in prevalence is attributable to social determinants of health, according to a recently published article in JAMA Network Open.

“There has been evidence from recent cohort studies in the U.S. that was suggesting that the prevalence and incidence [of gout] was growing among non-White populations,” said Natalie McCormick, PhD, the study’s lead author and postdoctoral research fellow in medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston. “We wanted to do this at the general population level to see how generalizable [that evidence] is.”

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Medical Group, Franklin, Wisc., noted the findings highlight inequities in care for patients with gout that could be improved with greater emphasis on educating patients about their condition.

“I think that what this shows is that in the U.S. ... there still are some disparities in treating gout,” said Dr. Wells, who was not involved with the study. “And that we have ways to mitigate that, with not only aggressive therapy, but also with other tools like counseling patients. At the end of the day, people all want to be educated about the disease.”
 

Greater prevalence disappears with adjustment for socioclinical factors

The cross-sectional analysis involved data from U.S. adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 who self-reported Black or White race.

Investigators considered factors such as excess body mass index (BMI), chronic kidney disease (defined as estimated glomerular filtration rate less than 60 mL/min per 1.73 m²), poverty, poor-quality diet, lower educational level, alcohol consumption, and diuretic use in their analysis.

Dr. McCormick and coinvestigators included a total of 18,693 participants, consisting of 3,304 Black women, 6,195 White women, 3,085 Black men, and 6,109 White men.

They determined that the age-standardized prevalence of gout was 3.5% (95% confidence interval, 2.7%-4.3%) in Black women and 2.0% (95% CI, 1.5% - 2.5%) in White women (age-adjusted odds ratio, 1.81; 95% CI, 1.29-2.53). They calculated that the prevalence was 7.0% (95% CI, 6.2%-7.9%) in Black men and 5.4% (95% CI, 4.7%-6.2%) in White men (age-adjusted OR, 1.26; 95% CI, 1.02-1.55). They found similar differences in the prevalence of hyperuricemia between Black and White Americans.

The increased prevalence of gout in Black Americans, compared with White Americans, does not arise from genetics, according to McCormick. “Our conclusion was that it was due to social determinants of health,” she said. “When we adjusted for all socioclinical risk factors, the racial differences in gout and hyperuricemia prevalence disappeared. Importantly, stepwise regression analysis showed the two biggest drivers of the racial difference in gout prevalence among women were poverty itself, and excess BMI, which can be influenced by poverty.”

Dr. McCormick pointed out that in contrast to the current data, there was no racial difference in the prevalence of gout approximately 2 decades earlier, looking at data from the 1988-1994 NHANES III.

Given the findings, which included the fact that significantly more Black women and men were currently taking diuretics, compared with their White counterparts, Dr. McCormick pointed out clinicians should give more thought to medical therapies prescribed for conditions like high blood pressure to patients with gout or at risk for gout.

“One thing we found was that diuretic use was a driver” of gout, Dr. McCormick said. A prescriber “may want to consider different therapies that present a lower risk of gout if someone has hypertension. There could be greater consideration for prescribing alternatives to diuretics.”

More patient education and rheumatology referrals needed

An impediment to providing that education to patients with gout is unconscious bias on the part of the primary care provider, Dr. Wells said.

“It is about what your perspectives are and what you bring to the table,” he explained. “If you saw [a patient] who looked like someone in your family, that person will be treated differently [than someone who does not look like a family member]. That is where the whole concept [of unconscious bias] comes in.”

Primary care providers need to adopt a holistic approach to gout management that involves counseling about good nutrition, smoking cessation, regular exercise, and limiting alcohol consumption, in addition to medication adherence. Primary care providers may have a bias in treating their Black patients, failing to devote sufficient time and attention to assist them in getting their disease under control, he said.

“Gout should be just like any other chronic disease,” Dr. Wells said. “You need to have a target in mind, and you and your patient need to work together to get to that target. When [patients] end up in rheumatology offices, it is almost too late. I think the take-home message here is that in 2022 ... for any patient who has gout, that patient probably needs to be seen by a rheumatologist because, indeed, with aggressive therapy, preventive therapy, [and] education, and if they are on the right medications, they won’t end up with these crippling joints that we see all the time.”

Dr. McCormick and Dr. Wells disclosed no relevant financial relationships.

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

Gout prevalence is more common in Black Americans than White Americans, and the disparity in prevalence is attributable to social determinants of health, according to a recently published article in JAMA Network Open.

“There has been evidence from recent cohort studies in the U.S. that was suggesting that the prevalence and incidence [of gout] was growing among non-White populations,” said Natalie McCormick, PhD, the study’s lead author and postdoctoral research fellow in medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston. “We wanted to do this at the general population level to see how generalizable [that evidence] is.”

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Medical Group, Franklin, Wisc., noted the findings highlight inequities in care for patients with gout that could be improved with greater emphasis on educating patients about their condition.

“I think that what this shows is that in the U.S. ... there still are some disparities in treating gout,” said Dr. Wells, who was not involved with the study. “And that we have ways to mitigate that, with not only aggressive therapy, but also with other tools like counseling patients. At the end of the day, people all want to be educated about the disease.”
 

Greater prevalence disappears with adjustment for socioclinical factors

The cross-sectional analysis involved data from U.S. adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 who self-reported Black or White race.

Investigators considered factors such as excess body mass index (BMI), chronic kidney disease (defined as estimated glomerular filtration rate less than 60 mL/min per 1.73 m²), poverty, poor-quality diet, lower educational level, alcohol consumption, and diuretic use in their analysis.

Dr. McCormick and coinvestigators included a total of 18,693 participants, consisting of 3,304 Black women, 6,195 White women, 3,085 Black men, and 6,109 White men.

They determined that the age-standardized prevalence of gout was 3.5% (95% confidence interval, 2.7%-4.3%) in Black women and 2.0% (95% CI, 1.5% - 2.5%) in White women (age-adjusted odds ratio, 1.81; 95% CI, 1.29-2.53). They calculated that the prevalence was 7.0% (95% CI, 6.2%-7.9%) in Black men and 5.4% (95% CI, 4.7%-6.2%) in White men (age-adjusted OR, 1.26; 95% CI, 1.02-1.55). They found similar differences in the prevalence of hyperuricemia between Black and White Americans.

The increased prevalence of gout in Black Americans, compared with White Americans, does not arise from genetics, according to McCormick. “Our conclusion was that it was due to social determinants of health,” she said. “When we adjusted for all socioclinical risk factors, the racial differences in gout and hyperuricemia prevalence disappeared. Importantly, stepwise regression analysis showed the two biggest drivers of the racial difference in gout prevalence among women were poverty itself, and excess BMI, which can be influenced by poverty.”

Dr. McCormick pointed out that in contrast to the current data, there was no racial difference in the prevalence of gout approximately 2 decades earlier, looking at data from the 1988-1994 NHANES III.

Given the findings, which included the fact that significantly more Black women and men were currently taking diuretics, compared with their White counterparts, Dr. McCormick pointed out clinicians should give more thought to medical therapies prescribed for conditions like high blood pressure to patients with gout or at risk for gout.

“One thing we found was that diuretic use was a driver” of gout, Dr. McCormick said. A prescriber “may want to consider different therapies that present a lower risk of gout if someone has hypertension. There could be greater consideration for prescribing alternatives to diuretics.”

More patient education and rheumatology referrals needed

An impediment to providing that education to patients with gout is unconscious bias on the part of the primary care provider, Dr. Wells said.

“It is about what your perspectives are and what you bring to the table,” he explained. “If you saw [a patient] who looked like someone in your family, that person will be treated differently [than someone who does not look like a family member]. That is where the whole concept [of unconscious bias] comes in.”

Primary care providers need to adopt a holistic approach to gout management that involves counseling about good nutrition, smoking cessation, regular exercise, and limiting alcohol consumption, in addition to medication adherence. Primary care providers may have a bias in treating their Black patients, failing to devote sufficient time and attention to assist them in getting their disease under control, he said.

“Gout should be just like any other chronic disease,” Dr. Wells said. “You need to have a target in mind, and you and your patient need to work together to get to that target. When [patients] end up in rheumatology offices, it is almost too late. I think the take-home message here is that in 2022 ... for any patient who has gout, that patient probably needs to be seen by a rheumatologist because, indeed, with aggressive therapy, preventive therapy, [and] education, and if they are on the right medications, they won’t end up with these crippling joints that we see all the time.”

Dr. McCormick and Dr. Wells disclosed no relevant financial relationships.

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

The U.S. Food and Drug Administration today approved a citrate-free, high-concentration formulation of adalimumab-bwwd (Hadlima), the manufacturer, Samsung Bioepis, and its commercialization partner Organon said in an announcement.

Hadlima is a biosimilar of the tumor necrosis factor inhibitor reference product adalimumab (Humira).

Hadlima was first approved in July 2019 in a citrated, 50-mg/mL formulation. The new citrate-free, 100-mg/mL version will be available in prefilled syringe and autoinjector options.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The 100-mg/mL formulation is indicated for the same seven conditions as its 50-mg/mL counterpart: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, and ulcerative colitis.

The approval was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of the 100-mg/mL and 50-mg/mL formulations of Hadlima in healthy volunteers.

Both low- and high-concentration formulations of Humira are currently marketed in the United States. Organon said that it expects to market Hadlima in the United States on or after July 1, 2023, in accordance with a licensing agreement with AbbVie.

The prescribing information for Hadlima includes specific warnings and areas of concern. The drug should not be administered to individuals who are known to be hypersensitive to adalimumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, including serious infections leading to hospitalization or death, such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections attributable to other opportunistic pathogens.

A test for latent TB infection should be given before administration, and treatment of TB should begin before administration of Hadlima.

Patients taking Hadlima should not take a live vaccine.

The most common adverse effects (incidence > 10%) include infections (for example, upper respiratory infections, sinusitis), injection site reactions, headache, and rash.

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

The U.S. Food and Drug Administration today approved a citrate-free, high-concentration formulation of adalimumab-bwwd (Hadlima), the manufacturer, Samsung Bioepis, and its commercialization partner Organon said in an announcement.

Hadlima is a biosimilar of the tumor necrosis factor inhibitor reference product adalimumab (Humira).

Hadlima was first approved in July 2019 in a citrated, 50-mg/mL formulation. The new citrate-free, 100-mg/mL version will be available in prefilled syringe and autoinjector options.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The 100-mg/mL formulation is indicated for the same seven conditions as its 50-mg/mL counterpart: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, and ulcerative colitis.

The approval was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of the 100-mg/mL and 50-mg/mL formulations of Hadlima in healthy volunteers.

Both low- and high-concentration formulations of Humira are currently marketed in the United States. Organon said that it expects to market Hadlima in the United States on or after July 1, 2023, in accordance with a licensing agreement with AbbVie.

The prescribing information for Hadlima includes specific warnings and areas of concern. The drug should not be administered to individuals who are known to be hypersensitive to adalimumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, including serious infections leading to hospitalization or death, such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections attributable to other opportunistic pathogens.

A test for latent TB infection should be given before administration, and treatment of TB should begin before administration of Hadlima.

Patients taking Hadlima should not take a live vaccine.

The most common adverse effects (incidence > 10%) include infections (for example, upper respiratory infections, sinusitis), injection site reactions, headache, and rash.

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

The U.S. Food and Drug Administration today approved a citrate-free, high-concentration formulation of adalimumab-bwwd (Hadlima), the manufacturer, Samsung Bioepis, and its commercialization partner Organon said in an announcement.

Hadlima is a biosimilar of the tumor necrosis factor inhibitor reference product adalimumab (Humira).

Hadlima was first approved in July 2019 in a citrated, 50-mg/mL formulation. The new citrate-free, 100-mg/mL version will be available in prefilled syringe and autoinjector options.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The 100-mg/mL formulation is indicated for the same seven conditions as its 50-mg/mL counterpart: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, and ulcerative colitis.

The approval was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of the 100-mg/mL and 50-mg/mL formulations of Hadlima in healthy volunteers.

Both low- and high-concentration formulations of Humira are currently marketed in the United States. Organon said that it expects to market Hadlima in the United States on or after July 1, 2023, in accordance with a licensing agreement with AbbVie.

The prescribing information for Hadlima includes specific warnings and areas of concern. The drug should not be administered to individuals who are known to be hypersensitive to adalimumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, including serious infections leading to hospitalization or death, such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections attributable to other opportunistic pathogens.

A test for latent TB infection should be given before administration, and treatment of TB should begin before administration of Hadlima.

Patients taking Hadlima should not take a live vaccine.

The most common adverse effects (incidence > 10%) include infections (for example, upper respiratory infections, sinusitis), injection site reactions, headache, and rash.

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

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.

The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching common in rheumatology, dermatology, and gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.

The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.

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

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.

The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching common in rheumatology, dermatology, and gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.

The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.

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

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.

The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching common in rheumatology, dermatology, and gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.

The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with psoriasis and psoriatic arthritis who belong to underserved groups may not be getting the health care they need because of lack of access, a study based on national registry data suggests.

“Using the All of Us dataset, we identified lower rates of psoriasis and psoriatic arthritis in participants with skin of color, lower education levels, and no health insurance,” lead author Megan M. Tran said in her oral presentation at the annual meeting of the Society for Investigative Dermatology.

“This suggests psoriasis and psoriatic arthritis underdiagnosis in these underserved populations, possibly due to limited dermatologic care access,” added Ms. Tran, a second-year medical student at Brown University in Providence, R.I.

Ms. Tran and colleagues used the ongoing National Institutes of Health All of Us Research Program registry that contains a large proportion of participants from groups in the United States who have historically been underrepresented in biomedical research, she said in her talk. 

Of the 329,038 participants with data in version 5 (released this past March) of the All of Us database, 150,158 (45.6%) had skin of color, and 251,597 (76.5%) had available electronic health records (EHRs).
 

Underserved groups need better access to health care

Linking data from EHRs, surveys, and physical measurements at enrollment, the researchers used several variables to estimate psoriasis and psoriatic arthritis (PsA) prevalence, and they used multivariate logistic regression to adjust for the variables. They found:

• Twenty-two percent of patients with psoriasis had PsA. Odds of psoriasis and PsA were lower among Black (psoriasis odds ratio [OR], 0.32, 95% confidence interval [CI], 0.28-0.36; PsA OR, 0.20, 95% CI, 0.15-0.26) and Hispanic participants (psoriasis OR, 0.77, 95% CI, 0.71-0.84; PsA OR, 0.74, 95% CI, 0.61-0.89) compared with White participants.
• Psoriasis prevalence increased linearly with age (topping off at age 70 and older [OR, 3.35, 95% CI, 2.91-3.88], with 18-29 years as the reference). The same trend was found with PsA (70 years and above [OR, 4.41, 95% CI, 3.07-6.55] compared with those aged 18-29 years).  
• Psoriasis prevalence increased linearly with body mass index (BMI 40 and above [OR, 1.71, 95% CI, 1.54-1.90], with 20-24.9 as the reference). The same trend was found with PsA (BMI 40 and above [OR, 2.09, 95% CI, 1.68-2.59], with 20-24.9 as the reference).  
• Former smokers were at increased risk for disease, compared with people who had never smoked (psoriasis OR, 1.30, 95% CI, 1.22-1.39; PsA OR, 2.15, 95% CI, 1.33-3.78).
• Lower odds were found in uninsured adults (psoriasis OR, 0.43, 95% CI, 0.35-0.52; PsA OR, 0.37, 95% CI, 0.22-0.58) compared with those who were insured, and in those with less than a high school degree (psoriasis OR, 0.72, 95% CI, 0.63-0.82; PsA OR, 0.65, 95% CI, 0.47-0.87) compared with those with a college degree.

“The All of Us research program has demonstrated to be a valuable resource to gain unique dermatologic insights on diverse participant populations,” Ms. Tran said.

“There needs to be improvement in access to quality dermatologic care, as this may help to reduce underdiagnosis of psoriasis and psoriatic arthritis,” she added. Access can be increased  in various ways, including “outreach to underserved communities, equitable distribution of resources, and increased awareness of clinical variations in skin of color.”

Laura Korb Ferris, MD, PhD, professor of dermatology and director of clinical trials for the department of dermatology at University of Pittsburgh Medical Center, said the study is interesting.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.

The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.

“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.

As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.

Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.

In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.

The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.

They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:

• Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
• Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
• The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
• In both tofacitinib groups, the probability of NSI increased before month 6.

The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
 

‘Best information to date’

Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.

“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.

“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.

Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.

Dr. Bhatt agreed.

“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.

Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.

“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.

He recommended further related research.

“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.

The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.

The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.

“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.

As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.

Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.

In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.

The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.

They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:

• Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
• Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
• The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
• In both tofacitinib groups, the probability of NSI increased before month 6.

The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
 

‘Best information to date’

Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.

“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.

“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.

Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.

Dr. Bhatt agreed.

“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.

Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.

“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.

He recommended further related research.

“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.

The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.

The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.

“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.

As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.

Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.

In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.

The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.

They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:

• Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
• Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
• The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
• In both tofacitinib groups, the probability of NSI increased before month 6.

The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
 

‘Best information to date’

Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.

“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.

“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.

Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.

Dr. Bhatt agreed.

“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.

Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.

“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.

He recommended further related research.

“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.

The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.

About two-thirds of children with juvenile idiopathic arthritis (JIA) were able to return to an inactive disease state within 12 months after a flare occurred when they took a break from medication, and slightly more than half – 55% – reached this state within 6 months, according to findings from registry data examined in a study published in Arthritis Care & Research.

Sarah Ringold, MD, MS, of the Seattle Children’s Hospital, and coauthors used data from participants in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry to track what happened to patients when they took a break from antirheumatic drugs. They described their paper as being the first to use a large multicenter database such as the CARRA Registry to focus on JIA outcomes after medication discontinuation and flare, to describe flare severity after medication discontinuation, and to report patterns of medication use for flares.

“To date, JIA studies have established that flares after medication discontinuation are common but have generated conflicting data regarding flare risk factors,” Dr. Ringold and coauthors wrote. “Since it is not yet possible to predict reliably which children will successfully discontinue medication, families and physicians face uncertainty when deciding to stop medications, and there is significant variation in approach.”

The study will be “very helpful” to physicians working with parents and patients to make decisions about discontinuing medications, said Grant Schulert, MD, PhD, of Cincinnati Children’s Hospital, who was not involved with the study.

“It gives some numbers to help us have those conversations,” he said in an interview.

But interpreting those numbers still will present parents with a challenge, Dr. Schulert said.

“You can say: ‘The glass is half full; 55% of them could go back into remission in 6 months, a little bit higher in a year,’ ” he said. “Or the glass is half empty; some of them, even at a year, are still not back in remission.”

But “patients aren’t a statistic. They’re each one person,” he said. “They’re going to be in one of those two situations.”

There are many challenges in explaining the potential advantages and disadvantages of medication breaks to patients and families, said the study’s senior author, Daniel B. Horton, MD, MSCE, of Rutgers Robert Wood Johnson Medical School and the Rutgers Center for Pharmacoepidemiology and Treatment Science, both in New Brunswick, N.J., and the department of biostatistics and epidemiology at Rutgers School of Public Health, Piscataway, N.J.

“One of the challenges of explaining the pros and cons about stopping medicines is the uncertainty – not knowing if and when a flare will occur, if and when a flare would be well controlled, and, for treatments that are continued, if and when complications of that treatment could occur,” Dr. Horton said in an interview. “Many patients and families are afraid about what the medicines might do long-term and want to stop treatment as soon as possible, despite the risks of stopping. Another challenge is that we do not yet have accurate, widely available tests that help us predict these various outcomes. Still, it is important for clinicians to explain the risks of continuing treatment and of stopping treatment, and to give patients and families time to ask questions and share their own values and preferences. If these conversations don’t happen, patients or families may just stop the medicines even if stopping is not warranted or is likely to lead to a poor outcome.”
 

Study details

Of the 367 patients studied, 270 (74%) were female. Half of all patients in the study had extended oligoarticular/rheumatoid factor (RF)–negative polyarticular JIA, and the second most common category was persistent oligoarthritis at 25%.The median age at disease onset was 4, with a range of 2-9 years.

The median age at disease flare was 11.3, with a range of 7.5-15.7 years. At the time of flare, children had a median disease duration of 5.1 years and had been off systemic disease-modifying antirheumatic drugs (DMARDs) for a median of 205 days. In addition, at the time of flare, the median active joint count was 1 and the maximum active joint count was 33, and approximately 13% of children had 5 or more active joints.

Conventional synthetic DMARDs were the most commonly stopped medications (48%), and tumor necrosis factor inhibitors (TNFi) were second (42%), Dr. Ringold and coauthors wrote.

Independent predictors of successful recapture of inactive disease included TNFi as recapture medication and history of a non-TNFi biologic use.

Dr. Ringold and coauthors noted limitations of the registry-based study. This is “a convenience sample of patients who are cared for and consented at academic sites, and additional study may be needed to understand how these results generalize to other countries and health systems,” they wrote.

And there may have been misclassification and inclusion of patients who stopped medications for self-perceived well-controlled disease, they wrote.

“Although the intent was to include children who stopped their medications at their physician’s direction due to physician-confirmed inactive disease, patients who had been previously enrolled in the registry were included if inactive disease was listed as the reason for medication discontinuation,” they said.

Still, these results should serve as a “benchmark for future studies of medication discontinuation” in JIA, the researchers wrote.
 

‘Fortunate challenge’

In an accompanying editorial, Melissa L. Mannion, MD, MSPH, and Randy Q. Cron, MD, PhD, of the University of Alabama at Birmingham noted that pediatric rheumatologists now face what they call the “fortunate challenge” of helping patients and parents decide whether treatments can be stopped in cases where there’s been a sustained period of inactive disease.

“Once a patient has reached the goal of inactive disease, why would patients or providers want to stop medications?” Dr. Mannion and Dr. Cron wrote. “We tell our patients that we want them to be like everyone else and have no limitations on their goals. However, the burden of chronic medication to achieve that goal is a constant reminder that they are different from their peers.”

In their article, Dr. Mannion and Dr. Cron noted what they called “interesting” results observed among children with different forms of JIA in the study.

Children with “systemic JIA had the highest recapture rates at 6 or 12 months, perhaps reflecting the high percentage use of [biologic] DMARDs targeting interleukin-1 and IL-6, or maybe the timeliness of recognition (e.g., fever, rash) of disease flare,” Dr. Mannion and Dr. Cron wrote. “Conversely, children with JIA enthesitis-related arthritis (ERA) had the lowest recapture rate at 6 months (27.6%, even lower than RF-positive polyarticular JIA, 42.9%).”

Still, the editorial authors said that “additional well-controlled studies are needed to move pediatric rheumatology deeper into the realm of precision medicine and the ability to decide whether or not to wean DMARD therapy for those with clinically inactive disease.”

Pamela Weiss, MD, of Children’s Hospital of Philadelphia, said in a comment that the study by Dr. Ringold and colleagues, as well as others that address similar questions, “are critically needed to move our field towards a personalized medicine approach.” But she added that while the paper from Dr. Ringold and colleagues addresses an important question, it “should be interpreted with some caution.”

She noted, for example, that “disease flare,” which prompted reinitiation of treatment and study entry, was not always aligned with a registry visit, which makes determination of the primary exposure less stringent. The rate of recapture across JIA categories differed by as much as 20% depending upon which inactive disease assessment outcome was used – either the study’s novel but unvalidated primary outcome or the validated secondary outcome of using the clinical Juvenile Arthritis Disease Activity Score based on 10 joints. The resulting difference was marked for some JIA categories and minimal for others.

“The flare and recapture rates are likely to be vastly different for JIA categories with distinct pathophysiology – namely systemic JIA, psoriatic arthritis, and enthesitis-related arthritis,” Dr. Weiss said. “While numbers for these categories were too small to make meaningful conclusions, grouping them with the other JIA categories has limitations.”

The research was funded by a Rheumatology Research Foundation Innovative Research Award.

Dr. Ringold’s current employment is through Janssen Research & Development. She changed primary employment from Seattle Children’s to Janssen during completion of the analyses and preparation of the manuscript. She has maintained her affiliation with Seattle Children’s. Dr. Schulert has consulting for Novartis. Dr. Cron reported speaker fees, consulting fees, and grant support from Sobi, consulting fees from Sironax and Novartis, speaker fees from Lilly, and support from Pfizer for working on a committee adjudicating clinical trial side effects.

* This article was updated on 8/11/2022.

About two-thirds of children with juvenile idiopathic arthritis (JIA) were able to return to an inactive disease state within 12 months after a flare occurred when they took a break from medication, and slightly more than half – 55% – reached this state within 6 months, according to findings from registry data examined in a study published in Arthritis Care & Research.

Sarah Ringold, MD, MS, of the Seattle Children’s Hospital, and coauthors used data from participants in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry to track what happened to patients when they took a break from antirheumatic drugs. They described their paper as being the first to use a large multicenter database such as the CARRA Registry to focus on JIA outcomes after medication discontinuation and flare, to describe flare severity after medication discontinuation, and to report patterns of medication use for flares.

“To date, JIA studies have established that flares after medication discontinuation are common but have generated conflicting data regarding flare risk factors,” Dr. Ringold and coauthors wrote. “Since it is not yet possible to predict reliably which children will successfully discontinue medication, families and physicians face uncertainty when deciding to stop medications, and there is significant variation in approach.”

The study will be “very helpful” to physicians working with parents and patients to make decisions about discontinuing medications, said Grant Schulert, MD, PhD, of Cincinnati Children’s Hospital, who was not involved with the study.

“It gives some numbers to help us have those conversations,” he said in an interview.

But interpreting those numbers still will present parents with a challenge, Dr. Schulert said.

“You can say: ‘The glass is half full; 55% of them could go back into remission in 6 months, a little bit higher in a year,’ ” he said. “Or the glass is half empty; some of them, even at a year, are still not back in remission.”

But “patients aren’t a statistic. They’re each one person,” he said. “They’re going to be in one of those two situations.”

There are many challenges in explaining the potential advantages and disadvantages of medication breaks to patients and families, said the study’s senior author, Daniel B. Horton, MD, MSCE, of Rutgers Robert Wood Johnson Medical School and the Rutgers Center for Pharmacoepidemiology and Treatment Science, both in New Brunswick, N.J., and the department of biostatistics and epidemiology at Rutgers School of Public Health, Piscataway, N.J.

“One of the challenges of explaining the pros and cons about stopping medicines is the uncertainty – not knowing if and when a flare will occur, if and when a flare would be well controlled, and, for treatments that are continued, if and when complications of that treatment could occur,” Dr. Horton said in an interview. “Many patients and families are afraid about what the medicines might do long-term and want to stop treatment as soon as possible, despite the risks of stopping. Another challenge is that we do not yet have accurate, widely available tests that help us predict these various outcomes. Still, it is important for clinicians to explain the risks of continuing treatment and of stopping treatment, and to give patients and families time to ask questions and share their own values and preferences. If these conversations don’t happen, patients or families may just stop the medicines even if stopping is not warranted or is likely to lead to a poor outcome.”
 

Study details

Of the 367 patients studied, 270 (74%) were female. Half of all patients in the study had extended oligoarticular/rheumatoid factor (RF)–negative polyarticular JIA, and the second most common category was persistent oligoarthritis at 25%.The median age at disease onset was 4, with a range of 2-9 years.

The median age at disease flare was 11.3, with a range of 7.5-15.7 years. At the time of flare, children had a median disease duration of 5.1 years and had been off systemic disease-modifying antirheumatic drugs (DMARDs) for a median of 205 days. In addition, at the time of flare, the median active joint count was 1 and the maximum active joint count was 33, and approximately 13% of children had 5 or more active joints.

Conventional synthetic DMARDs were the most commonly stopped medications (48%), and tumor necrosis factor inhibitors (TNFi) were second (42%), Dr. Ringold and coauthors wrote.

Independent predictors of successful recapture of inactive disease included TNFi as recapture medication and history of a non-TNFi biologic use.

Dr. Ringold and coauthors noted limitations of the registry-based study. This is “a convenience sample of patients who are cared for and consented at academic sites, and additional study may be needed to understand how these results generalize to other countries and health systems,” they wrote.

And there may have been misclassification and inclusion of patients who stopped medications for self-perceived well-controlled disease, they wrote.

“Although the intent was to include children who stopped their medications at their physician’s direction due to physician-confirmed inactive disease, patients who had been previously enrolled in the registry were included if inactive disease was listed as the reason for medication discontinuation,” they said.

Still, these results should serve as a “benchmark for future studies of medication discontinuation” in JIA, the researchers wrote.
 

‘Fortunate challenge’

In an accompanying editorial, Melissa L. Mannion, MD, MSPH, and Randy Q. Cron, MD, PhD, of the University of Alabama at Birmingham noted that pediatric rheumatologists now face what they call the “fortunate challenge” of helping patients and parents decide whether treatments can be stopped in cases where there’s been a sustained period of inactive disease.

“Once a patient has reached the goal of inactive disease, why would patients or providers want to stop medications?” Dr. Mannion and Dr. Cron wrote. “We tell our patients that we want them to be like everyone else and have no limitations on their goals. However, the burden of chronic medication to achieve that goal is a constant reminder that they are different from their peers.”

In their article, Dr. Mannion and Dr. Cron noted what they called “interesting” results observed among children with different forms of JIA in the study.

Children with “systemic JIA had the highest recapture rates at 6 or 12 months, perhaps reflecting the high percentage use of [biologic] DMARDs targeting interleukin-1 and IL-6, or maybe the timeliness of recognition (e.g., fever, rash) of disease flare,” Dr. Mannion and Dr. Cron wrote. “Conversely, children with JIA enthesitis-related arthritis (ERA) had the lowest recapture rate at 6 months (27.6%, even lower than RF-positive polyarticular JIA, 42.9%).”

Still, the editorial authors said that “additional well-controlled studies are needed to move pediatric rheumatology deeper into the realm of precision medicine and the ability to decide whether or not to wean DMARD therapy for those with clinically inactive disease.”

Pamela Weiss, MD, of Children’s Hospital of Philadelphia, said in a comment that the study by Dr. Ringold and colleagues, as well as others that address similar questions, “are critically needed to move our field towards a personalized medicine approach.” But she added that while the paper from Dr. Ringold and colleagues addresses an important question, it “should be interpreted with some caution.”

She noted, for example, that “disease flare,” which prompted reinitiation of treatment and study entry, was not always aligned with a registry visit, which makes determination of the primary exposure less stringent. The rate of recapture across JIA categories differed by as much as 20% depending upon which inactive disease assessment outcome was used – either the study’s novel but unvalidated primary outcome or the validated secondary outcome of using the clinical Juvenile Arthritis Disease Activity Score based on 10 joints. The resulting difference was marked for some JIA categories and minimal for others.

“The flare and recapture rates are likely to be vastly different for JIA categories with distinct pathophysiology – namely systemic JIA, psoriatic arthritis, and enthesitis-related arthritis,” Dr. Weiss said. “While numbers for these categories were too small to make meaningful conclusions, grouping them with the other JIA categories has limitations.”

The research was funded by a Rheumatology Research Foundation Innovative Research Award.

Dr. Ringold’s current employment is through Janssen Research & Development. She changed primary employment from Seattle Children’s to Janssen during completion of the analyses and preparation of the manuscript. She has maintained her affiliation with Seattle Children’s. Dr. Schulert has consulting for Novartis. Dr. Cron reported speaker fees, consulting fees, and grant support from Sobi, consulting fees from Sironax and Novartis, speaker fees from Lilly, and support from Pfizer for working on a committee adjudicating clinical trial side effects.

* This article was updated on 8/11/2022.

About two-thirds of children with juvenile idiopathic arthritis (JIA) were able to return to an inactive disease state within 12 months after a flare occurred when they took a break from medication, and slightly more than half – 55% – reached this state within 6 months, according to findings from registry data examined in a study published in Arthritis Care & Research.

Sarah Ringold, MD, MS, of the Seattle Children’s Hospital, and coauthors used data from participants in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry to track what happened to patients when they took a break from antirheumatic drugs. They described their paper as being the first to use a large multicenter database such as the CARRA Registry to focus on JIA outcomes after medication discontinuation and flare, to describe flare severity after medication discontinuation, and to report patterns of medication use for flares.

“To date, JIA studies have established that flares after medication discontinuation are common but have generated conflicting data regarding flare risk factors,” Dr. Ringold and coauthors wrote. “Since it is not yet possible to predict reliably which children will successfully discontinue medication, families and physicians face uncertainty when deciding to stop medications, and there is significant variation in approach.”

The study will be “very helpful” to physicians working with parents and patients to make decisions about discontinuing medications, said Grant Schulert, MD, PhD, of Cincinnati Children’s Hospital, who was not involved with the study.

“It gives some numbers to help us have those conversations,” he said in an interview.

But interpreting those numbers still will present parents with a challenge, Dr. Schulert said.

“You can say: ‘The glass is half full; 55% of them could go back into remission in 6 months, a little bit higher in a year,’ ” he said. “Or the glass is half empty; some of them, even at a year, are still not back in remission.”

But “patients aren’t a statistic. They’re each one person,” he said. “They’re going to be in one of those two situations.”

There are many challenges in explaining the potential advantages and disadvantages of medication breaks to patients and families, said the study’s senior author, Daniel B. Horton, MD, MSCE, of Rutgers Robert Wood Johnson Medical School and the Rutgers Center for Pharmacoepidemiology and Treatment Science, both in New Brunswick, N.J., and the department of biostatistics and epidemiology at Rutgers School of Public Health, Piscataway, N.J.

“One of the challenges of explaining the pros and cons about stopping medicines is the uncertainty – not knowing if and when a flare will occur, if and when a flare would be well controlled, and, for treatments that are continued, if and when complications of that treatment could occur,” Dr. Horton said in an interview. “Many patients and families are afraid about what the medicines might do long-term and want to stop treatment as soon as possible, despite the risks of stopping. Another challenge is that we do not yet have accurate, widely available tests that help us predict these various outcomes. Still, it is important for clinicians to explain the risks of continuing treatment and of stopping treatment, and to give patients and families time to ask questions and share their own values and preferences. If these conversations don’t happen, patients or families may just stop the medicines even if stopping is not warranted or is likely to lead to a poor outcome.”
 

Study details

Of the 367 patients studied, 270 (74%) were female. Half of all patients in the study had extended oligoarticular/rheumatoid factor (RF)–negative polyarticular JIA, and the second most common category was persistent oligoarthritis at 25%.The median age at disease onset was 4, with a range of 2-9 years.

The median age at disease flare was 11.3, with a range of 7.5-15.7 years. At the time of flare, children had a median disease duration of 5.1 years and had been off systemic disease-modifying antirheumatic drugs (DMARDs) for a median of 205 days. In addition, at the time of flare, the median active joint count was 1 and the maximum active joint count was 33, and approximately 13% of children had 5 or more active joints.

Conventional synthetic DMARDs were the most commonly stopped medications (48%), and tumor necrosis factor inhibitors (TNFi) were second (42%), Dr. Ringold and coauthors wrote.

Independent predictors of successful recapture of inactive disease included TNFi as recapture medication and history of a non-TNFi biologic use.

Dr. Ringold and coauthors noted limitations of the registry-based study. This is “a convenience sample of patients who are cared for and consented at academic sites, and additional study may be needed to understand how these results generalize to other countries and health systems,” they wrote.

And there may have been misclassification and inclusion of patients who stopped medications for self-perceived well-controlled disease, they wrote.

“Although the intent was to include children who stopped their medications at their physician’s direction due to physician-confirmed inactive disease, patients who had been previously enrolled in the registry were included if inactive disease was listed as the reason for medication discontinuation,” they said.

Still, these results should serve as a “benchmark for future studies of medication discontinuation” in JIA, the researchers wrote.
 

‘Fortunate challenge’

In an accompanying editorial, Melissa L. Mannion, MD, MSPH, and Randy Q. Cron, MD, PhD, of the University of Alabama at Birmingham noted that pediatric rheumatologists now face what they call the “fortunate challenge” of helping patients and parents decide whether treatments can be stopped in cases where there’s been a sustained period of inactive disease.

“Once a patient has reached the goal of inactive disease, why would patients or providers want to stop medications?” Dr. Mannion and Dr. Cron wrote. “We tell our patients that we want them to be like everyone else and have no limitations on their goals. However, the burden of chronic medication to achieve that goal is a constant reminder that they are different from their peers.”

In their article, Dr. Mannion and Dr. Cron noted what they called “interesting” results observed among children with different forms of JIA in the study.

Children with “systemic JIA had the highest recapture rates at 6 or 12 months, perhaps reflecting the high percentage use of [biologic] DMARDs targeting interleukin-1 and IL-6, or maybe the timeliness of recognition (e.g., fever, rash) of disease flare,” Dr. Mannion and Dr. Cron wrote. “Conversely, children with JIA enthesitis-related arthritis (ERA) had the lowest recapture rate at 6 months (27.6%, even lower than RF-positive polyarticular JIA, 42.9%).”

Still, the editorial authors said that “additional well-controlled studies are needed to move pediatric rheumatology deeper into the realm of precision medicine and the ability to decide whether or not to wean DMARD therapy for those with clinically inactive disease.”

Pamela Weiss, MD, of Children’s Hospital of Philadelphia, said in a comment that the study by Dr. Ringold and colleagues, as well as others that address similar questions, “are critically needed to move our field towards a personalized medicine approach.” But she added that while the paper from Dr. Ringold and colleagues addresses an important question, it “should be interpreted with some caution.”

She noted, for example, that “disease flare,” which prompted reinitiation of treatment and study entry, was not always aligned with a registry visit, which makes determination of the primary exposure less stringent. The rate of recapture across JIA categories differed by as much as 20% depending upon which inactive disease assessment outcome was used – either the study’s novel but unvalidated primary outcome or the validated secondary outcome of using the clinical Juvenile Arthritis Disease Activity Score based on 10 joints. The resulting difference was marked for some JIA categories and minimal for others.

“The flare and recapture rates are likely to be vastly different for JIA categories with distinct pathophysiology – namely systemic JIA, psoriatic arthritis, and enthesitis-related arthritis,” Dr. Weiss said. “While numbers for these categories were too small to make meaningful conclusions, grouping them with the other JIA categories has limitations.”

The research was funded by a Rheumatology Research Foundation Innovative Research Award.

Dr. Ringold’s current employment is through Janssen Research & Development. She changed primary employment from Seattle Children’s to Janssen during completion of the analyses and preparation of the manuscript. She has maintained her affiliation with Seattle Children’s. Dr. Schulert has consulting for Novartis. Dr. Cron reported speaker fees, consulting fees, and grant support from Sobi, consulting fees from Sironax and Novartis, speaker fees from Lilly, and support from Pfizer for working on a committee adjudicating clinical trial side effects.

* This article was updated on 8/11/2022.

More than half of patients with noninfectious acute anterior uveitis seen in ophthalmology clinics in a new cross-sectional study were found by rheumatologists to have spondyloarthritis (SpA), prompting the researchers to recommend referring “all patients with AAU reporting musculoskeletal symptoms to rheumatologists.”

The results also suggest that “rheumatologists should consider that SpA in AAU patients might present ‘atypically’ with no or mild back pain starting after the age of 45 years and lasting shorter than 3 months,” according to first author Judith Rademacher, MD, and colleagues at Charité–Universitätsmedizin Berlin, who published their work online in Arthritis & Rheumatology.

Jonathan Trobe, M.D./Wikimedia Commons/CC BY-SA 3.0

During July 2017–April 2021, the study team prospectively assessed 189 consecutive adult patients with noninfectious AAU at ophthalmology clinics in the Berlin area. The patients had rheumatologic examinations and underwent pelvic x-ray if they had back pain as well as MRI of sacroiliac joints regardless of back pain unless there was a contraindication. The patients had a mean age of nearly 41 years, and 54.5% were male.

Of the 189 patients with AAU, the researchers diagnosed SpA in 106, including 74 (70%) who had been previously undiagnosed. A total of 99 (93%) had predominately axial SpA, and 7 (7%) had peripheral SpA.

A multivariable logistic regression assessment found that male sex (odds ratio, 2.1; 95% confidence interval, 1.1-4.2), HLA-B27 positivity (OR, 6.3; 95% CI, 2.4-16.4), elevated C-reactive protein (OR, 4.8; 95% CI, 1.9-12.4), and psoriasis (OR, 12.5; 95% CI, 1.3-120.2) were significantly associated with SpA in patients with AAU. No ophthalmologic factors were significantly associated with SpA.

Among all patients, an adaptation of the Assessment of SpondyloArthritis International Society (ASAS) referral tool demonstrated lower specificity for SpA recognition than did the Dublin Uveitis Evaluation Tool (28% vs. 42%). The ASAS referral took had a slightly greater sensitivity than the Dublin Uveitis Evaluation Tool (80% vs. 78%).

“Taking into account only AAU patients without prior diagnosis of SpA, a rheumatologist would have to see 2.1 patients fulfilling the ASAS tool or 1.9 patients fulfilling the DUET to diagnose one patient with SpA. However, with both referral strategies more than 20% of SpA patients would have been missed,” the researchers wrote. “This might be due to an ‘unusual presentation’ of SpA in those patients as their back pain started more often after the age of 45 years, lasted shorter than 3 months and thus, ASAS classification criteria were less frequently fulfilled.”

The researchers acknowledged possible selection bias because 15 patients with an incomplete rheumatologic evaluation were excluded. MRI also was routinely done for sacroiliac joints alone, although it was possible for clinician to order spinal MRI. In addition, the researchers allowed patients with AAU into the study regardless of their current treatment, meaning that it may have been possible for some patients receiving biologic disease-modifying antirheumatic drugs to not be correctly identified as having SpA if the treatment improved their musculoskeletal symptoms.

Expert commentary

There are a number of diseases associated with SpA, including AAU, noted Kristine Kuhn, MD, PhD, an associate professor of medicine at the University of Colorado at Denver, Aurora, who was not involved in the study.

“As a rheumatologist, we are quite aware of [uveitis] as an association, and we are usually asking our patients about eye symptoms because of this association,” Dr. Kuhn said in an interview.

While just over half of the patients with AAU also met the criteria for SpA, “that doesn’t necessarily mean diagnosis per se because classification criteria are based on a series of features to homogenize a group of people for clinical research studies. So it doesn’t always align 100% with diagnosis, but it does give us an indication that a little of over half of people with anterior uveitis will have underlying spondyloarthritis and should be evaluated by a rheumatologist.”

Dr. Kuhn also highlighted the associations of male sex, HLA-B27 positivity, and concomitant presence of psoriasis. “I bring those up because I find those to be interesting associations. We have known those for years to be associated with axial spondyloarthritis, but when you look at the actual data, I would just put a little bit of caution to those conclusions.”

She pointed out that, although the link of male sex to SpA in patients with AAU was statistically significant, it is not a clinically meaningful association.

Dr. Kuhn also noted that caution should be used when interpreting the HLA-B27 positivity data. “The caution that I put there is that this was conducted in Germany, and we know that Northern European populations tend to be more enriched for HLA-B27 genes, so what that association would be in a more diverse population is unknown.

“I think ophthalmologists are really good when they see a patient with [acute]-onset anterior uveitis; they have a suspicion that there’s probably another systemic disease that they should be looking at. What this tells us as a physician community is that maybe we should lower the threshold for getting patients into rheumatology and looking at whether or not the patient has underlying spondyloarthritis,” she said.

AbbVie supported the study with an unrestricted research grant but had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Of the study’s 12 authors, 2 reported having no financial disclosures. All others reported financial relationships with pharmaceutical companies, including AbbVie.

More than half of patients with noninfectious acute anterior uveitis seen in ophthalmology clinics in a new cross-sectional study were found by rheumatologists to have spondyloarthritis (SpA), prompting the researchers to recommend referring “all patients with AAU reporting musculoskeletal symptoms to rheumatologists.”

The results also suggest that “rheumatologists should consider that SpA in AAU patients might present ‘atypically’ with no or mild back pain starting after the age of 45 years and lasting shorter than 3 months,” according to first author Judith Rademacher, MD, and colleagues at Charité–Universitätsmedizin Berlin, who published their work online in Arthritis & Rheumatology.

Jonathan Trobe, M.D./Wikimedia Commons/CC BY-SA 3.0

During July 2017–April 2021, the study team prospectively assessed 189 consecutive adult patients with noninfectious AAU at ophthalmology clinics in the Berlin area. The patients had rheumatologic examinations and underwent pelvic x-ray if they had back pain as well as MRI of sacroiliac joints regardless of back pain unless there was a contraindication. The patients had a mean age of nearly 41 years, and 54.5% were male.

Of the 189 patients with AAU, the researchers diagnosed SpA in 106, including 74 (70%) who had been previously undiagnosed. A total of 99 (93%) had predominately axial SpA, and 7 (7%) had peripheral SpA.

A multivariable logistic regression assessment found that male sex (odds ratio, 2.1; 95% confidence interval, 1.1-4.2), HLA-B27 positivity (OR, 6.3; 95% CI, 2.4-16.4), elevated C-reactive protein (OR, 4.8; 95% CI, 1.9-12.4), and psoriasis (OR, 12.5; 95% CI, 1.3-120.2) were significantly associated with SpA in patients with AAU. No ophthalmologic factors were significantly associated with SpA.

Among all patients, an adaptation of the Assessment of SpondyloArthritis International Society (ASAS) referral tool demonstrated lower specificity for SpA recognition than did the Dublin Uveitis Evaluation Tool (28% vs. 42%). The ASAS referral took had a slightly greater sensitivity than the Dublin Uveitis Evaluation Tool (80% vs. 78%).

“Taking into account only AAU patients without prior diagnosis of SpA, a rheumatologist would have to see 2.1 patients fulfilling the ASAS tool or 1.9 patients fulfilling the DUET to diagnose one patient with SpA. However, with both referral strategies more than 20% of SpA patients would have been missed,” the researchers wrote. “This might be due to an ‘unusual presentation’ of SpA in those patients as their back pain started more often after the age of 45 years, lasted shorter than 3 months and thus, ASAS classification criteria were less frequently fulfilled.”

The researchers acknowledged possible selection bias because 15 patients with an incomplete rheumatologic evaluation were excluded. MRI also was routinely done for sacroiliac joints alone, although it was possible for clinician to order spinal MRI. In addition, the researchers allowed patients with AAU into the study regardless of their current treatment, meaning that it may have been possible for some patients receiving biologic disease-modifying antirheumatic drugs to not be correctly identified as having SpA if the treatment improved their musculoskeletal symptoms.

Expert commentary

There are a number of diseases associated with SpA, including AAU, noted Kristine Kuhn, MD, PhD, an associate professor of medicine at the University of Colorado at Denver, Aurora, who was not involved in the study.

“As a rheumatologist, we are quite aware of [uveitis] as an association, and we are usually asking our patients about eye symptoms because of this association,” Dr. Kuhn said in an interview.

While just over half of the patients with AAU also met the criteria for SpA, “that doesn’t necessarily mean diagnosis per se because classification criteria are based on a series of features to homogenize a group of people for clinical research studies. So it doesn’t always align 100% with diagnosis, but it does give us an indication that a little of over half of people with anterior uveitis will have underlying spondyloarthritis and should be evaluated by a rheumatologist.”

Dr. Kuhn also highlighted the associations of male sex, HLA-B27 positivity, and concomitant presence of psoriasis. “I bring those up because I find those to be interesting associations. We have known those for years to be associated with axial spondyloarthritis, but when you look at the actual data, I would just put a little bit of caution to those conclusions.”

She pointed out that, although the link of male sex to SpA in patients with AAU was statistically significant, it is not a clinically meaningful association.

Dr. Kuhn also noted that caution should be used when interpreting the HLA-B27 positivity data. “The caution that I put there is that this was conducted in Germany, and we know that Northern European populations tend to be more enriched for HLA-B27 genes, so what that association would be in a more diverse population is unknown.

“I think ophthalmologists are really good when they see a patient with [acute]-onset anterior uveitis; they have a suspicion that there’s probably another systemic disease that they should be looking at. What this tells us as a physician community is that maybe we should lower the threshold for getting patients into rheumatology and looking at whether or not the patient has underlying spondyloarthritis,” she said.

AbbVie supported the study with an unrestricted research grant but had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Of the study’s 12 authors, 2 reported having no financial disclosures. All others reported financial relationships with pharmaceutical companies, including AbbVie.

More than half of patients with noninfectious acute anterior uveitis seen in ophthalmology clinics in a new cross-sectional study were found by rheumatologists to have spondyloarthritis (SpA), prompting the researchers to recommend referring “all patients with AAU reporting musculoskeletal symptoms to rheumatologists.”

The results also suggest that “rheumatologists should consider that SpA in AAU patients might present ‘atypically’ with no or mild back pain starting after the age of 45 years and lasting shorter than 3 months,” according to first author Judith Rademacher, MD, and colleagues at Charité–Universitätsmedizin Berlin, who published their work online in Arthritis & Rheumatology.

Jonathan Trobe, M.D./Wikimedia Commons/CC BY-SA 3.0

During July 2017–April 2021, the study team prospectively assessed 189 consecutive adult patients with noninfectious AAU at ophthalmology clinics in the Berlin area. The patients had rheumatologic examinations and underwent pelvic x-ray if they had back pain as well as MRI of sacroiliac joints regardless of back pain unless there was a contraindication. The patients had a mean age of nearly 41 years, and 54.5% were male.

Of the 189 patients with AAU, the researchers diagnosed SpA in 106, including 74 (70%) who had been previously undiagnosed. A total of 99 (93%) had predominately axial SpA, and 7 (7%) had peripheral SpA.

A multivariable logistic regression assessment found that male sex (odds ratio, 2.1; 95% confidence interval, 1.1-4.2), HLA-B27 positivity (OR, 6.3; 95% CI, 2.4-16.4), elevated C-reactive protein (OR, 4.8; 95% CI, 1.9-12.4), and psoriasis (OR, 12.5; 95% CI, 1.3-120.2) were significantly associated with SpA in patients with AAU. No ophthalmologic factors were significantly associated with SpA.

Among all patients, an adaptation of the Assessment of SpondyloArthritis International Society (ASAS) referral tool demonstrated lower specificity for SpA recognition than did the Dublin Uveitis Evaluation Tool (28% vs. 42%). The ASAS referral took had a slightly greater sensitivity than the Dublin Uveitis Evaluation Tool (80% vs. 78%).

“Taking into account only AAU patients without prior diagnosis of SpA, a rheumatologist would have to see 2.1 patients fulfilling the ASAS tool or 1.9 patients fulfilling the DUET to diagnose one patient with SpA. However, with both referral strategies more than 20% of SpA patients would have been missed,” the researchers wrote. “This might be due to an ‘unusual presentation’ of SpA in those patients as their back pain started more often after the age of 45 years, lasted shorter than 3 months and thus, ASAS classification criteria were less frequently fulfilled.”

The researchers acknowledged possible selection bias because 15 patients with an incomplete rheumatologic evaluation were excluded. MRI also was routinely done for sacroiliac joints alone, although it was possible for clinician to order spinal MRI. In addition, the researchers allowed patients with AAU into the study regardless of their current treatment, meaning that it may have been possible for some patients receiving biologic disease-modifying antirheumatic drugs to not be correctly identified as having SpA if the treatment improved their musculoskeletal symptoms.

Expert commentary

There are a number of diseases associated with SpA, including AAU, noted Kristine Kuhn, MD, PhD, an associate professor of medicine at the University of Colorado at Denver, Aurora, who was not involved in the study.

“As a rheumatologist, we are quite aware of [uveitis] as an association, and we are usually asking our patients about eye symptoms because of this association,” Dr. Kuhn said in an interview.

While just over half of the patients with AAU also met the criteria for SpA, “that doesn’t necessarily mean diagnosis per se because classification criteria are based on a series of features to homogenize a group of people for clinical research studies. So it doesn’t always align 100% with diagnosis, but it does give us an indication that a little of over half of people with anterior uveitis will have underlying spondyloarthritis and should be evaluated by a rheumatologist.”

Dr. Kuhn also highlighted the associations of male sex, HLA-B27 positivity, and concomitant presence of psoriasis. “I bring those up because I find those to be interesting associations. We have known those for years to be associated with axial spondyloarthritis, but when you look at the actual data, I would just put a little bit of caution to those conclusions.”

She pointed out that, although the link of male sex to SpA in patients with AAU was statistically significant, it is not a clinically meaningful association.

Dr. Kuhn also noted that caution should be used when interpreting the HLA-B27 positivity data. “The caution that I put there is that this was conducted in Germany, and we know that Northern European populations tend to be more enriched for HLA-B27 genes, so what that association would be in a more diverse population is unknown.

“I think ophthalmologists are really good when they see a patient with [acute]-onset anterior uveitis; they have a suspicion that there’s probably another systemic disease that they should be looking at. What this tells us as a physician community is that maybe we should lower the threshold for getting patients into rheumatology and looking at whether or not the patient has underlying spondyloarthritis,” she said.

AbbVie supported the study with an unrestricted research grant but had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Of the study’s 12 authors, 2 reported having no financial disclosures. All others reported financial relationships with pharmaceutical companies, including AbbVie.

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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