Abstract Introduction/objective Janus kinase inhibitors (JAKi’s) have shown promising results in systemic sclerosis (SSc), yet little studied. We evaluated safety and intra-patient changes in pulmonary, articular, and cutaneous parameters in SSc JAKi-treated patients. Methods An international, multi-centre, longitudinal retrospective cohort study. We assessed changes in FVC%, DLCO%, modified Rodnan skin score (mRSS), tender/swollen joint counts (TJC/SJC), digital ulcers (DU), and calcinosis. Baseline was defined as JAKi initiation. Outcomes were analysed as delta from baseline using Wilcoxon signed-rank tests, with effect sizes expressed as standardized mean change (SMC). Results Among 32 patients treated with the four available JAKi’s, median (IQR) follow-up was 16.9 (10.3, 31.8) months, totalling 52.8 patient-years. At 12 months, pulmonary function remained stable (SMC = + 0.22 for FVC%, + 0.23 for DLCO%; p = 0.10 and p = 0.33, respectively). mRSS (SMC = − 0.29, p = 0.03), TJC and SJC (SMC = − 1.19 and − 0.69, p < 0.001 and p = 0.001, respectively) significantly improved. At 24 months, numerical improvements in mRSS, TJC, and SJC persisted with SMC of − 0.21, − 1.13, and − 1.14 ( p = 0.17, p = 0.054, p = 0.058, respectively). Among 11 patients with baseline calcinosis, 45.5% improved. Ten patients developed DUs. In 15 patients receiving glucocorticoids, a non-significant trend toward tapering was observed. Conclusion JAKi treatment in SSc patients was associated with ‘real-world’ improvements in multiple domains; findings are exploratory. Key Points • JAKi treatment in SSc patients was associated with ‘real-world’ improvements in multiple clinically important domains. • Relevant safety concerns with JAKi treatment were confirmed in our treated SSc patient cohort. • Our findings provide preliminary real-world evidence supporting a potential role of JAK inhibitors across multiple clinical domains in SSc. • Long-term controlled trials to confirm the safety and efficacy of JAKi’s in patients with SSc are needed.
Donato et al. (Sat,) studied this question.