Effectiveness and safety of upadacitinib in refractory pediatric inflammatory bowel disease: A single-arm meta-analysis of observational studies

Background: Upadacitinib (UPA), a selective Janus kinase-1 (JAK-1) inhibitor, has been approved for adults with refractory inflammatory bowel disease (IBD). Its oral formulation and efficacy after biologic failures make it an attractive option for children with refractory IBD. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of UPA in children with moderate to severe IBD. Methods: We systematically searched PubMed, Embase, and the Cochrane Library until May 2025. Studies were included if they involved pediatric IBD patients (<18 years) treated with UPA and reported clinical or endoscopic outcomes. We excluded case reports/series with ≤5 patients, studies using multiple dual therapies, or those lacking predefined outcomes. Pooled rates were calculated using a random-effects model. Results: Five retrospective studies, involving 248 patients (134 with ulcerative colitis (UC) and 114 with Crohn’s disease (CD), met the inclusion criteria. Post-induction, the pooled clinical response rate was 88% (95% CI: 76%–96%; I2 = 58.9%), and the steroid-free clinical remission (SFCR) rate was 70% (95% CI: 54%–85%; I2 = 69%). The rates for endoscopic response and remission were 82% (95% CI: 57%–98%; I2 = 0%) and 36% (95% CI: 11%–64%; I2 = 0%), respectively. During maintenance, SFCR rate was 76% (95% CI: 59%–89%; I2 = 0%). Serious adverse events occurred at a rate of 9 per 100 person-years, with herpes zoster reactivation at 4 per 100 person-years. No venous thromboembolic events were reported. Conclusions: UPA may offer a therapeutic alternative for refractory pediatric IBD, but its efficacy and safety require prospective validation.