Should You Interrupt Arthritis DMARDs During an Infection?

When patients with inflammatory arthritis develop an infection while taking immunomodulatory drugs, temporarily interrupting the therapy does not improve outcomes, according to results from one of the most useful and clinically relevant studies in rheumatology presented last year, experts said at the 2025 Rheumatology Winter Clinical Symposium (RWCS) during a year-in-review of papers and abstracts.

The multicenter, Dutch, open-label, randomized controlled trial of 1142 patients with rheumatoid arthritis (RA; 61%), psoriatic arthritis (29%), or spondyloarthritis (10%) found that continuing immunomodulatory therapy during a clinically relevant infection “absolutely made no difference” over temporarily stopping therapy when it came to the risk of progressing to a serious infection (one requiring hospitalization or intravenous treatment), said Jack Cush, MD, executive editor of RheumNow.com.

“It answers the question [that arises] with your RA patient who is doing well and gets an infection: What are you going to do with their therapy?” Cush said. “Many people knee-jerk it and say, ‘Let’s just stop the therapy.’ But in general, by doing so, you’re starting the cascade of getting the patient into trouble by interrupting therapy that’s working.”

Patients in the study — presented in an abstract session at the American College of Rheumatology 2024 Annual Meeting and in a poster at the European Alliance of Associations for Rheumatology 2024 Annual Meeting — were randomized 1:1 into continuation or temporary interruption of their immunomodulatory agent during their first clinically relevant infection. Immunomodulatory agents included monotherapy with biologic, targeted synthetic, or conventional disease-modifying antirheumatic drugs or combinations. The randomized assignment was stratified for the use of tumor necrosis factor inhibitors, oral glucocorticoids, and risk for severe COVID-19.

During a total follow-up time of 1667 patient-years, 474 patients developed a clinically relevant infection (241 and 233 in the continuation and interruption arms, respectively) and were included in the study’s intention-to-treat population.

Serious infections subsequently developed in 21 of these 474 patients: 5.15% of patients in the temporary interruption group and 3.73% in the continuation group. The adjusted risk difference was 1.7% (95% CI, 2-5.4). Analyses of different subsets of patients (eg, use of oral glucocorticoids or history of previous serious infection) showed similar adjusted risk differences, the study investigators reported.

“These were pretty run-of-the-mill, nonserious infections” in the intention-to-treat group, Cush said. “And 21 out of [474] — that’s low.”

Arthur Kavanaugh, MD, who co-presented the RWCS 2025 year-in-review session with Cush and is professor of medicine at the University of California, San Diego, said in an email interview after the meeting that the study is significant because “there is very little data in this area” amid ongoing concerns about the risk for infectious events occurring and of more serious outcomes when infections occur (eg, bronchitis becoming pneumonia) in patients taking immunomodulatory therapies.

In general, he said, rheumatologists respond on the basis of the seriousness of the event, stopping immunomodulatory therapies for patients who are hospitalized for their infections but possibly not stopping them for patients with seemingly mild infections. They also consider other factors such as comorbid conditions, concomitant medications (especially steroids), the patient’s general health, and potential outcomes (eg, outcomes of an infection of a newly replaced joint), said Kavanaugh.

In an email, Co-author Nathan den Broeder, PhD, a researcher in rheumatology at Sint Maartenskliniek, a multispecialty clinic in Nijmegen, the Netherlands, said that drug labels often recommend temporary discontinuation in the case of intercurrent infection, but practice guidelines tend not to address the issue.

Current practice in Europe “varies strongly,” he said, but overall, “many [lean toward] the cautious approaching of stopping the immunomodulatory agent during infection.” One center declined to participate in the study “because they felt that continuing these drugs during infection was too risky,” he noted.

An earlier interview study done by the Dutch team and involving both patients and healthcare providers identified 10 themes that play a role in the decision-making process about the use of immunomodulatory drugs in infections. These include immune-mediated inflammatory disease activity and characteristics of the agent, of the patient, and of the infection, the researchers reported in 2023.

One author of the 2024 study of continuation vs interruption reported financial relationships with AbbVie, Celltrion, Gilead Sciences, and several other companies.