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

Abstract 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.