Superior drug retention of selective JAK1 inhibitors compared to pan-JAK inhibitors in rheumatoid arthritis: A meta-analysis of real-world evidence.

PURPOSE: The durability of Janus kinase (JAK) inhibitors in routine clinical practice is still debated. This study aimed to compare the drug retention rates of selective JAK1 inhibitors (upadacitinib, filgotinib) with pan-JAK inhibitors (tofacitinib, baricitinib) in patients with rheumatoid arthritis (RA) using real-world data.

METHODS

We conducted a systematic literature search in PubMed, Embase, and the Cochrane Library for observational studies published up to December 2025. The analysis included registry-based cohorts and claims database studies that compared drug retention between selective JAK1 and pan-JAK inhibitors in adult RA patients. The primary outcome was the overall risk of drug discontinuation, with pooled Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) calculated using a random-effects model.

RESULTS

Seven studies involving 21,244 patients from Europe, Asia, and the United States met the inclusion criteria. Patients treated with selective JAK1 inhibitors had a significantly lower risk of drug discontinuation compared to those on pan-JAK inhibitors (pooled HR 0.72; 95% CI 0.61-0.85; p < 0.001). Subgroup analyses showed that selective JAK1 inhibitors had a significantly reduced risk of discontinuation due to lack of efficacy (pooled HR 0.68; 95% CI 0.55-0.84; p < 0.01). However, the risks of discontinuation due to adverse events (pooled HR 0.91; 95% CI 0.75-1.10; p = 0.34) and infections (pooled HR 1.15; 95% CI 0.85-1.55; p = 0.40) were similar between the groups.

CONCLUSION

Real-world evidence indicates that selective JAK1 inhibitors offer better drug retention than pan-JAK inhibitors in RA patients, primarily due to sustained effectiveness rather than differences in safety profiles.