Temporarily pausing biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) following a COVID booster vaccine did not enhance immunogenicity in people with autoimmune diseases, according to results from a large randomized clinical trial. At the same time, the pause in treatment led to an increase in disease flares.

“Patients with inflammatory arthritis had significant humoral responses after COVID-19 supplemental dose vaccination, yet holding biologic or [Janus kinase] JAK inhibitor therapy for 2 weeks did not enhance immunogenicity in any drug category or half-life stratum,” study authors, led by first author Jeffrey Curtis, MD, MPH, professor of medicine in the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham, wrote. “Given the increased flare risk and absence of humoral immunogenicity benefit, these findings do not support routine temporary interruption for COVID-19 vaccine optimization.”

The report was published online on October 5 in JAMA Internal Medicine. Some of the results were previously presented at the 2024 American College of Rheumatology Annual Meeting.

Clinicians have had no hard evidence on this topic prior to the current investigation, according to Laura Cappelli, MD, MHS, an associate professor of medicine in the Division of Rheumatology at Johns Hopkins School of Medicine in Baltimore, who was not affiliated with the study.

“The effects of holding biologics and JAK inhibitors after COVID vaccination on vaccine efficacy and disease activity have been unknown,” Cappelli told Medscape Medical News. “Counseling patients with inflammatory arthritis on how to manage their medications around COVID vaccination has been based on anecdotal and indirect evidence.”

The multicenter, randomized, pragmatic clinical trial enrolled 840 patients with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis. All participants had previously received a primary COVID vaccine and were receiving stable immunomodulatory therapy with TNF inhibitors, interleukin (IL)-17 inhibitors, abatacept, and/or JAK inhibitors. Patients were randomly assigned to either continue or hold therapy for 2 weeks following COVID supplemental dose administration.

The study’s primary outcome was the change in immunoglobulin G levels against the SARS-CoV-2 spike protein from baseline to 6-week follow-up, as measured using geometric mean fold rise (GMFR) ratio. The investigation followed an intention-to-treat framework but also included a per-protocol sensitivity analysis.

In the primary analysis, the GMFR ratio (hold/continue) was 0.96 (95% CI, 0.36-2.56), indicating no significant difference between the two study arms. Results were consistent across drug subgroups and drug half-life categories.

In the primary intention-to-treat analysis, both arms demonstrated significant increases in anti-receptor-binding domain (RBD) immunoglobulin G antibody-based immunogenicity from baseline, with no significant differences between study arms.

“Antibody responses increased substantially in both groups. So essentially, holding treatment did not have benefit in terms of the frequency of patients that developed antibodies against RBD,” said Inés Colmegna, MD, an associate professor of rheumatology at McGill University, Montréal, Quebec, Canada, who has conducted evaluations of vaccine responses in rheumatic diseases but was not affiliated with the study.

Holding therapy markedly increased disease flare risk. Self-reported post-vaccine flares or worsening of disease was significantly higher in the hold arm (intention-to-treat odds ratio [OR], 2.27; 95% CI, 1.41-3.65; per-protocol OR, 2.60; 95% CI, 1.67-4.03). Flare risk was most elevated among JAK inhibitor users (OR, 3.65; 95% CI, 1.69-7.87), with odds not differing significantly among abatacept, IL-17 inhibitors, or TNF inhibitors.

“There’s no benefit [to holding] in terms of immunogenicity, and there is clearly an increase in the number of patients that flared,” Colmegna noted. “So because of that reason, for clinicians, I think this is a study that is informative and helps them to deal with this particular question in this group of patients.”

Adverse events were comparable between medication arms and were more frequent in the hold group, study authors reported.

According to Cappelli, the findings indicated that clinicians should avoid counseling patients with autoimmune diseases to temporarily discontinue DMARD therapy for supplemental COVID vaccinations.

“If you can vaccinate patients before starting biologics or JAK inhibitors, you should try to do so,” Cappelli said. “Otherwise, I would not hold TNF inhibitors, abatacept, IL-17 inhibitors, or JAK inhibitors when patients get a COVID-19 vaccination.”

The trial was funded by AbbVie, Bristol Myers Squibb, Lilly, Novartis, and Pfizer. A grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases provided additional infrastructure support. Cappelli reported receiving consulting fees from AbbVie, Artiva Biotherapeutics, and Sanofi, and grant/research support from Bristol Myers Squibb and AstraZeneca. Colmegna reported no relevant disclosures.

Scott Harris has been covering rheumatology for more than a decade. He lives near Washington, DC.