Interferon Levels Predict Early Relapse of RA After bDMARD Discontinuation

blood test for analysis
Researchers analyzed the biomarkers which distinguish early from late relapses after biologics withdrawal among patients with rheumatoid arthritis.

Serum levels of interferon beta (IFNβ) predict early relapse of rheumatoid arthritis (RA) within 6 months following withdrawal from biologic disease-modifying antirheumatic drug (bDMARD) treatment in patients who achieved clinical remission, according to study findings published in Scientific Reports.

Researchers in Japan conducted a post-hoc analysis of their prospective cohort study using data from patients with RA who achieved clinical remission for more than 12 months during treatment with bDMARDs, specifically tumor necrosis factor inhibitors (TNFis) and interleukin (IL)-6 inhibitors.

At bDMARD discontinuation, patients provided serum samples at baseline and the following 4 weeks for the next 24 months as long as they remained in clinical remission.

The researchers analyzed 73 potential cytokine biomarkers to determine if they differentiated early from late relapses of RA after bDMARD discontinuation.

Of the 40 patients included in the study, 14 achieved sustained clinical remission of RA until 2 years following bDMARD withdrawal. The remaining 26 patients had relapse, of which 13 occurred within 6 months (early relapse) and 13 occurred after 6 months (late relapse) of bDMARD withdrawal.

Higher concentrations of IFNβ corresponded consistently with early relapse of RA across time points, including baseline measurements. IFNβ was the only predictive cytokine biomarker identified for early relapse.

An increased weekly dose of methotrexate at baseline correlated with later relapses (P =.047), while an increased daily dose of prednisolone at baseline correlated with earlier relapses (P =.037).

“High serum levels of IFNβ in the early-relapse group remained high until actual relapse occurred. Therefore, patients who relapse early might be biochemically different from those who relapse late or do not relapse at all,” the study authors said. “We recommend that patients who are predicted to relapse early continue bDMARDs even if they are in complete remission. This finding contributes to shared decision-making regarding how and when bDMARDs should be discontinued,” they added.


Sakashita E, Nagatani K, Endo H, Minota S. Serum level of IFNβ distinguishes early from late relapses after biologics withdrawal in rheumatoid arthritis. Sci Rep. 2022;12(1):16547. doi:10.1038/s41598-022-21160-0