Are Janus kinase inhibitors safe and effective in treating the key clinical domains of psoriatic arthritis? A systematic review and meta-analysis.

Abstract

Psoriatic arthritis (PsA), is a complex inflammatory arthropathy with a heterogenous spectrum of disease presentation. Despite the vast therapeutic armamentarium, disease control in a considerable proportion of patients is suboptimal. The aim of this study was to assess the safety and efficacy of Janus kinase inhibitors (JAKi), in the management of key clinical domains of PsA including peripheral arthritis, psoriasis, enthesitis and dactylitis. Randomized placebo-controlled trials (RCTs) of JAKi in PsA were identified by a systematic literature search using EMBASE, PubMed and CENTRAL. All included studies underwent meta-analysis. A total of 5 RCTs were included. Patients were randomized to tofacitinib (n=474), filgotinib (n=65), upadacitinib (n=1281) or placebo (n=937). JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo: American College of Rheumatology (ACR) 20 (risk ratio [RR] 2.10, [95% CI 1.86-2.37], P< .00001, I2=19%); ACR 50 (RR 3.43, [95% CI 2.37-4.96], P< .00001, I2=66%); ACR 70 (RR 4.57, [95% CI 1.83-11.44], P= .001, I2=82%); Psoriasis Area and Severity Index 75 (RR 2.96, [95% CI 2.44-3.58], P< .00001, I2=0%); enthesitis resolution (RR 1.82, [95% CI 1.56-2.12], P< .00001, I2=0%); and dactylitis resolution (RR 1.85, [95% CI 1.57-2.16], P< .00001, I2=0%). JAKi were associated with an overall increased risk of adverse events (RR 1.14, [95% CI 1.07-1.21], P= .0001, I2=0%) with increased risk of infection (RR1.23, [95% CI 1.08-1.39], P= .001, I2=0%) vs placebo. This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA. However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile.