A 6-year prospective observational study examined whether baricitinib provides similar clinical outcomes when used as monotherapy or in combination with methotrexate in patients with rheumatoid arthritis, offering new evidence to guide treatment decisions in routine care settings.
The study, published in RMD Open, followed 219 patients with rheumatoid arthritis (RA) who initiated baricitinib at a single tertiary center between 2017 and 2023. Clinical, laboratory, and patient-reported outcomes were collected every 3 months. Of the cohort, 165 patients received baricitinib monotherapy, while 54 received baricitinib in combination with methotrexate (MTX). Treatment decisions reflected standard clinical practice rather than randomization.
At treatment initiation, patients had moderate to high disease activity, with a mean Disease Activity Score 28 joints with erythrocyte sedimentation rate (DAS28-ESR) of approximately 4.0. Both monotherapy and combination therapy groups showed rapid improvement, with disease activity declining within the first 6 months and remaining stable over long-term follow-up. Overall, 33% of patients achieved Boolean remission at least once during observation, with no statistically significant difference between treatment strategies.
Long-term drug survival, a key indicator of effectiveness and tolerability in routine care, was also similar between groups. Median baricitinib persistence was 36 months, and Kaplan-Meier analyses showed no meaningful differences in treatment continuation over 72 months. Discontinuations were most commonly due to lack of efficacy, adverse events, remission, or reassessment of cardiovascular risk.
Safety outcomes were consistent with the known profile of baricitinib. Adverse events leading to treatment discontinuation occurred in 11% of patients. Four thrombotic events were reported, all in patients with preexisting cardiovascular risk factors. No new safety signals, malignancies, or unexpected cardiovascular events emerged during extended follow-up. Dose reductions from 4 mg to 2 mg were documented in a subset of patients, most often because of sustained remission, and were generally well tolerated.
Although some disease activity measures and patient-reported outcomes numerically favored combination therapy, these differences were small and not statistically significant. The researchers caution that the single-center, nonrandomized design limits causal interpretation and does not support conclusions about superiority of one approach over the other.
For practicing rheumatologists, the key takeaway is practical rather than comparative. MTX intolerance, contraindications, and patient preference frequently limit combination therapy in long-term RA management. In this real-world cohort, baricitinib monotherapy achieved sustained disease control, remission rates, drug survival, and tolerability comparable to combination therapy, offering reassurance when MTX is not suitable.
The researchers emphasize that treatment decisions should remain individualized, particularly given ongoing safety considerations surrounding Janus kinase inhibitors. While randomized trials remain essential for establishing comparative efficacy, these long-term observational data provide clinically relevant reassurance supporting baricitinib monotherapy as a viable option in appropriate patients, wrote lead author Sara Bayat, MD, of Friedrich-Alexander-Universität Erlangen-Nürnberg in Germany, and colleagues.
The authors declared having no competing interests.
Source: RMD Open
