Upadacitinib is associated with clinical response and steroid-free remission for children and adolescents with inflammatory bowel disease.

Objective: Upadacitinib, an oral Janus kinase inhibitor (JAKi), is approved for inflammatory bowel disease (IBD) in adults. As on-label use will face significant delay in pediatrics, a real-world understanding of safety and efficacy in children is critical.

Methods: This is a single-center retrospective cohort of pediatric subjects (ages 9-20 years) with a diagnosis of IBD initiated on upadacitinib. The primary outcome was clinical response following induction (decrease of ≥20 points in the Pediatric Ulcerative Colitis Activity Index [PUCAI] or ≥12.5 points for the Pediatric Crohn's Disease Activity Index [PCDAI]). Secondary outcomes included steroid-free clinical remission (SF-CR) following induction and at Week 24 (PUCAI or PCDAI ≤10), post-induction mucosal response and remission (Mayo for ulcerative colitis [UC]/IBD-unclassified [IBD-U] and simple-endoscopic scoring for CD), and improvement in calprotectin and C-reactive protein (CRP) post-induction. Monitoring for adverse events was recorded.

Results: Twenty subjects (40% female with a median age of 16.3 years; 3 CD, 13 UC, 4 IBD-U) were initiated on upadacitinib. Clinical response at Week 8 (UC/IBD-U) and Week 12 (CD), was achieved in 90% (18/20). SF-CR was seen in 75% (16/20) following induction and maintained in 65% (11/17) reaching Week 24 of therapy. In subjects with UC/IBD-U (17), PUCAI was significantly improved at Weeks 8 and 24. Calprotectin post-induction showed a significant downtrend, whereas CRP did not. Endoscopic response was noted in seven of the eight cases, with three achieving endoscopic remission. One patient underwent subtotal colectomy after 2 weeks of upadacitinib induction. Another patient stopped therapy following the creation of a diverting ileostomy secondary to rectal perforation experienced following manual dilation of a rectal stricture. No new safety signals were reported.

Conclusion: Therapeutic options for children with IBD remain limited. In cases refractory to approved agents, our experience suggests that upadacitinib is effective with no new safety signals in a small subset of patients with IBD (ages 9-20 years) treated at a children's hospital.