Systematic review and meta-analysis supports adalimumab plus methotrexate for JIA-associated uveitis

BACKGROUND: Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a leading cause of preventable visual loss in children. Whether adalimumab should be initiated with, and continued on, background methotrexate (MTX) remains a pivotal therapeutic question. OBJECTIVE: To synthesize randomized evidence on the efficacy and safety of initiating and continuing adalimumab with MTX in children with JIA-U. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) through May 2025. The primary outcome was time-to-treatment failure or relapse. Hazard ratios (HRs) were pooled using a random-effects model after harmonizing effect direction so that HR < 1 favored adalimumab. Secondary outcomes included control of ocular inflammation, visual acuity, corticosteroid-sparing, and safety. RESULTS: Three RCTs met inclusion; two contributed time-to-event data to meta-analysis ( = 177). Pooled results showed a substantial reduction in treatment failure/relapse with adalimumab plus MTX (HR 0.18; 95% CI 0.09-0.39; I = 42.7%). The third RCT demonstrated early suppression of intraocular inflammation by laser flare photometry during the blinded phase. Across trials, adalimumab facilitated corticosteroid tapering and preserved visual acuity. Adverse events were comparable between groups, with few serious events and no emergent safety signals. CONCLUSIONS: Initiating adalimumab on MTX, and maintaining therapy once remission is achieved, markedly lowers relapse risk and supports steroid-sparing while preserving vision in pediatric JIA-U. These findings endorse adalimumab with MTX as the preferred strategy across initiation and continuation scenarios.