Mirikizumab Shows Early Efficacy in Pediatric UC in SHINE-2 Trial

Mirikizumab induction produced early clinical, endoscopic, and symptomatic improvements in children and adolescents with moderately to severely active ulcerative colitis (UC), according to week 12 data from the phase 3 SHINE-2 study presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.1

Results showed that at week 12, 41.3% of participants aged 2 to 17 years achieved clinical remission, and 81.0% achieved clinical response.1

Mirikizumab is a humanized monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, with established efficacy in adults with UC.² In the phase 2 SHINE-1 study of 26 pediatric patients, 69.2% had clinical response and 38.5% had clinical remission at week 12.3 The investigators, led by Marla Dubinsky, MD, of Icahn School of Medicine at Mount Sinai, described SHINE-2 as the first phase 3 evidence of mirikizumab efficacy and safety in pediatric UC.1

How Was SHINE-2 Designed?

SHINE-2 was an open-label phase 3 study enrolling 63 participants aged 2 to 17 years with a modified Mayo score of 5 to 9 and an endoscopic subscore of ≥ 2. All participants had an inadequate response, loss of response, or intolerance to ≥ 1 conventional or advanced therapy. Among the cohort, the mean age was 13.2 years, 76.2% were 12 years or older, and 54.0% had prior biologic failure.1

Participants received weight-based intravenous induction every 4 weeks for 3 doses: 300 mg for those weighing > 40 kg and 5 mg/kg for those weighing ≤ 40 kg.1 Responders then received subcutaneous maintenance every 4 weeks at 200 mg, 100 mg, or 50 mg, depending on weight.

Because the study had no concurrent placebo arm, investigators compared pediatric outcomes with historical results from the adult phase 3 LUCENT program. The primary endpoint, clinical remission at week 52 among week 12 responders, was evaluated using a Bayesian approach incorporating adult mirikizumab data.1,2

What Did Mirikizumab Achieve at Week 12 in Children With UC?

At week 12, pediatric rates exceeded historical adult placebo rates for clinical remission (41.3% vs 14.6%), clinical response (81.0% vs 43.4%), endoscopic remission (25.4% vs 4.5%), and endoscopic improvement (50.8% vs 21.0%). Pediatric Ulcerative Colitis Activity Index (PUCAI) remission was achieved by 58.7% of participants, and PUCAI response by 87.3%.1

Symptomatic remission was observed in 38.1% of participants by week 4 and in 69.8% by week 12. Mean fecal calprotectin decreased from 3734 µg/g at baseline to 1649 µg/g at week 12.1

By week 52, 50.0% of week 12 clinical responders were in clinical remission, compared with 50.7% among adults receiving mirikizumab and 26.6% among adults receiving placebo in LUCENT-2. The lower bound of the pediatric 80% credible interval (42.8%) exceeded the upper bound of the adult placebo 90% credible interval (32.6%), meeting the prespecified success criterion.1

What Did Safety and Pharmacokinetic Data Show?

Through week 12, 65.1% of participants had ≥ 1 treatment-emergent adverse event, all mild or moderate. The most common were upper respiratory tract infection (12.7%), headache (11.1%), and anemia (7.9%). No deaths occurred.1

Two participants (3.2%) had serious adverse events, one UC flare and one large intestine polyp, and one participant discontinued treatment because of a UC flare.1 The investigators reported a safety profile consistent with prior mirikizumab studies, with no new safety signals.

Pharmacokinetic analyses from weeks 16 to 52 showed mirikizumab exposures with weight-based dosing were generally comparable across pediatric weight subgroups and with adults.1 Only 4 participants weighed ≤ 20 kg, which limited assessment of the lowest weight category.

References

1. Dubinsky M, Bousvaros A, Griffiths AM, et al. Mirikizumab induction therapy achieves early clinical, endoscopic, and biomarker improvement in children and adolescents with moderately to severely active ulcerative colitis: week 12 results from the SHINE-2 study. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2023;388(26):2444-2455. doi:10.1056/NEJMoa2207940

3. Kaplan JL, Bousvaros A, Turner D, et al. 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. Lancet Gastroenterol Hepatol. 2026;11(2):100-109. doi:10.1016/S2468-1253(25)00196-7