Upadacitinib and upadacitinib-vedolizumab combination therapy for refractory pediatric-onset inflammatory bowel...

To evaluate the efficacy and safety of upadacitinib in patients with highly refractory pediatric-onset inflammatory bowel disease (IBD) and to describe the outcomes of upadacitinib-vedolizumab combination therapy (UVCT) in treatment-refractory cases.

This retrospective, single-center study included 18 patients (7 with ulcerative colitis, 6 with Crohn's disease, and 5 with very early-onset IBD) who received upadacitinib between November 2022 and November 2025. Five patients underwent UVCT. All patients had previously failed multiple therapies (median, 3 prior advanced therapies). The primary outcome was the upadacitinib continuation rate. The secondary outcomes included corticosteroid- and tacrolimusfree remission rates, safety profiles, and UVCT outcomes.

The median age at upadacitinib initiation was 13.0 years (range, 2.3-21.6 years). The 52-week continuation rate was 55.6%. Among patients who received corticosteroids at baseline, 50% achieved corticosteroid-free status by 6 months; all patients who received tacrolimus at baseline discontinued tacrolimus within 6 months. No serious adverse events attributable to upadacitinib were observed and no cases of herpes zoster reactivation occurred. Five patients with persistent corticosteroid/tacrolimus dependence underwent UVCT, 4 of whom achieved clinical remission with withdrawal of corticosteroids/tacrolimus, with endoscopic improvement confirmed in 3. One patient with very early-onset IBD required colectomy.

Upadacitinib demonstrated acceptable efficacy and safety in patients with highly refractory pediatric-onset IBD. In this small subgroup, UVCT was associated with clinical remission in most patients (4/5), suggesting that it may warrant further investigation as a salvage strategy to avert surgery. Prospective, multicenter studies are needed to define the optimal positioning within pediatric-onset IBD treatment algorithms.