Briefly noted:

Jess L et al. The Lancet Gastroenterology & Hepatology 2025; 11: 100 – 109. Efficacy and safety of mirikizumab in paediatric participants with moderately-to-severely active ulcerative colitis (SHINE-1): a multicentre, open-label, non-randomised phase 2 trial

Background: Mirikizumab, a immunoglobulin G4 monoclonal antibody, targets the p19 subunit of IL-23, with demonstrated efficacy and safety in adults with ulcerative colitis and Crohn’s disease.

Methods: This 52-week, multicenter, open-label, non-randomized, phase 2 study enrolled pediatric participants (n=26, 2 to <18 years) with moderately-to-severely active ulcerative colitis with inadequate or loss of response or intolerance to corticosteroids, immunomodulators, biologics, or JAK inhibitors.

Key findings:

•  At week 12: 18 (69·2%) participants had a clinical response by modified Mayo score (mMS), ten (38·5%) achieved clinical remission by mMS, 14 (53·8%) achieved endoscopic remission
• At week 12: 20 (76·9%) of the 26 participants had a clinical response based on Pediatric Ulcerative Colitis Activity Index (PUCAI), and ten (38·5%) achieved clinical remission at week 12
• At week 52: 14 (53·8%) of 26 participants achieved mMS-based clinical response, ten (38·5%) were in mMS-based clinical remission, ten (38·5%, 95% CI 22·4–57·5) of 26 patients were in endoscopic remission
• At week 52:  14 (53·8%) had a PUCAI-based clinical response and 13 (50·0%) were in PUCAI-based clinical remission
• Three (12%) participants experienced serious adverse events across induction and maintenance periods (non-infective appendicitis, worsening of ulcerative colitis, and pseudarthrosis), of which one (worsening of ulcerative colitis) led to study discontinuation

My take: In this pediatric population with high prior advanced therapy exposure, there was a good response to mirikizumab. This trial which was limited by a lack of an active comparator group was started prior to the medication approval in adults. Overall, the IL-23 class of medications has emerged as an effective drug class for inflammatory bowel disease.

Related blog posts:

• Efficacy of Mirikizumab in Ulcerative Colitis: LUCENT-3 Study Results
• Efficacy of Mirikizumab in Moderate-to-Severe Crohn’s Disease (VIVID-1 Study)
• Prior Exposure to TNF Antagonists May Increase Response to JAK Inhibitors in Patients with Ulcerative Colitis
• IBD Updates: Extending Mirkizumab Induction, Best Biologic, Fatigue in Pediatric IBD, Adalimumab Success in Patients with Abdominal Abscess
• In Trials: An Oral IL-23 Antagonist Peptide
• Over 60% of Initial Nonresponders Improve with Extended Risankizumab Therapy for Crohn’s Disease
• Crohn’s Disease: Risankizumab Real-World Data
• Risankizumab Outperforms Ustekinumab
• Risankizumab for Ulcerative Colitis
• Dr. Maria Oliva-Hemker: Positioning Therapies for Pediatric Crohn’s Disease