2036: JAK1 selective inhibitors versus pan-JAK inhibitors: comparative real-world study of drug retention in chronic inflammatory arthritis

Background/Purpose: Janus kinase inhibitors (JAKis) are effective therapeutic agents against chronic inflammatory arthritis (CIA). Tofacitinib and baricitinib were defined as pan-JAK inhibitors, while upadacitinib and filgotinib a JAK1 selective inhibitors. Real world data comparing retention rate across JAKi classes in CIA are limited. The aim of the present study was to compare retention rate between pan-JAK inhibitors and JAK1 selective inhibitors in CIA and to assess the role of JAKi class in the risk of discontinuation and find out other possible predictors of treatment discontinuation.

Methods: We retrospectively evaluated patients with CIA [Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Spondyloarthritis (SPA)] treated with JAKis from 2017 to 2024. The independent variable was JAKi class (pan-JAK inhibitors/ JAK1 selective inhibitors). Retention rates were assessed by Kaplan–Meier method, and multivariable Cox regression hazards model was run to identified predictors of discontinuation.

Results: The study comprised 181 patients [83% women, median age 56(49-63)]. 84% had RA, 9% PsA and 7% SpA. Patients received 227 JAKi treatments courses, 96 of JAK1 selective inhibitors y 131 of pan-JAK inhibitors. Overall, 118 courses (52%) were discontinued (55% inefficacy, 42% adverse events, 3% other). The estimated IR of discontinuation was 35.5 [29.6-42.5] and 50% of them discontinued within 1.65 [1.2-2.2] years after JAKI starting. The IR of discontinuation was higher in women, and in those with cardiovascular disease or risk factors, being lower for RA vs other CIAs. Discontinuation rates were lower for JAK1-selective inhibitors (IR: 28.6; 95% CI: 20.5–39.8) vs pan-JAK inhibitors (IR: 39.6; 95% CI: 31.9–49.1). In the multivariate analysis, pan-JAK inhibitors, female gender, PsA, cardiovascular disease, previous b/tsDMARDs courses, cardiovascular risk factors, and leflunomide combined treatment were associated with higher probability of discontinuation.

Conclusion: Pan-JAK inhibitors (baricitinib and tofacitinib) may have higher discontinuation rates than JAK1 selective inhibitors is (upadacitinib and filgotinib) patients with CIAs in real-world settings. Several clinical factors, including diagnosis and comorbidities, influence JAKi retention and should guide treatment selection.