JAK Inhibitors in Inflammatory Skin Diseases: A 15,427-Patient Systematic Review and Meta-analysis of Clinical Trial and Real-World Outcomes.

Abstract

Background: Janus kinase (JAK) inhibitors are a new class of medications that are changing how we treat inflammatory skin diseases. Even though these drugs are increasingly being approved for various skin conditions, there is still limited detailed comparison of their effectiveness, safety, and long-term effects across different diseases.

Objective: In this study, we systematically evaluated the use of JAK inhibitors in atopic dermatitis, psoriasis, vitiligo, alopecia areata, and hidradenitis suppurativa across both trial and real-world settings.

Methods: We conducted a systematic review following PRISMA 2020 guidelines and searched major databases for randomized controlled trials (RCTs), open-label extensions, and real-world cohort studies published through May 2025. The main effectiveness outcomes included disease-specific measures: Eczema Area and Severity Index (EASI) for atopic dermatitis, Psoriasis Area and Severity Index (PASI) for psoriasis, Severity of Alopecia Tool (SALT) for alopecia areata, Vitiligo Area Scoring Index (VASI) for vitiligo, and Hidradenitis Suppurativa Clinical Response (HiSCR) for hidradenitis suppurativa. Safety outcomes included rates of adverse events, infections, thromboembolism, and cancer. Patient-centered outcomes included quality of life (DLQI) and pruritus reduction. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0 (RoB 2).

Results: We included 68 studies (42 RCTs, 14 open-label extensions, and 12 real-world cohorts) with 15,427 patients across five inflammatory skin diseases. Oral JAK inhibitors demonstrated efficacy across multiple conditions compared with placebo, with EASI-75 response rates ranging from 38 to 73% in atopic dermatitis, PASI-75 rates ranging from 33 to 67% in psoriasis, and SALT-50 rates from 30 to 62% in alopecia areata. Topical JAK inhibitors have proven effective for atopic dermatitis and vitiligo but have shown limited benefit in alopecia areata. Safety profiles were generally similar across drugs, with higher rates of upper respiratory infections (5-14%) and herpes zoster reactivation (1-3%) compared with placebo. Serious adverse events, such as major cardiovascular events, venous thromboembolism, and cancers, were rare but did occur.

Conclusions: JAK inhibitors demonstrate significant efficacy across several inflammatory skin diseases, with a safety profile that warrants ongoing monitoring, particularly in patients with cardiovascular risk factors. Comparative data suggest that selective JAK1 inhibitors appear to offer the most favorable balance between efficacy and safety for atopic dermatitis, whereas JAK1/2 inhibitors showed numerically higher efficacy for alopecia areata, though this difference did not reach statistical significance. However, the interpretation of long-term safety and comparative effectiveness is constrained by the limited duration of controlled trials, under-representation of diverse populations, and reliance on indirect comparisons. PROSPERO registration: CRD420251045477.