Efficacy and Safety of Janus Kinase Inhibitors in Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis...

To assess the efficacy and safety of Janus kinase inhibitors (JAKi) in patients with active systemic lupus erythematosus (SLE).

We conducted a systematic review of randomized, double-blind, placebo-controlled phase 2 and 3 trials involving JAKi in adults with active SLE. Five trials (n=1802) were included, evaluating baricitinib 4 mg (n=3), deucravacitinib 3 mg twice daily (n=1), and upadacitinib 30 mg (n=1). The primary outcome was the SLE Responder Index-4 (SRI-4) response at weeks 24 to 52. Secondary outcomes included the BICLA response, Lupus Low Disease Activity State (LLDAS), and safety endpoints such as serious adverse events, serious infections, herpes zoster, and venous thromboembolism. Pooled odds ratios (ORs) were calculated using random-effects Mantel-Haenszel models.

JAKi significantly improved the SRI-4 response compared with placebo (54.4% vs. 43.8%; OR: 1.78, 95% CI: 1.41-2.25; p<0.001; I²=32%). Improvements were also observed in BICLA (OR: 1.92, 95% CI: 1.53-2.41) and LLDAS (OR: 2.01, 95% CI: 1.58-2.56). However, serious adverse events (OR: 1.48, 95% CI: 1.03-2.13) and serious infections (OR: 2.10, 95% CI: 1.21-3.65) occurred more frequently with JAKi, primarily driven by herpes zoster (OR: 3.24, 95% CI: 1.92-5.46). The rates of venous thromboembolism were comparable (OR: 1.13, 95% CI: 0.44-2.94).

JAKi significantly improved disease activity across various composite endpoints in active SLE, demonstrating an acceptable safety profile characterized by an increased risk of herpes zoster but no evident signal for venous thromboembolism.