Highlights
– Mirikizumab, an anti–IL-23 p19 monoclonal antibody, produced clinical response in 69% of paediatric participants at week 12 and maintained response in 54% at week 52 (modified Mayo score).
– Endoscopic remission was achieved in 54% at week 12 and 38% at week 52; symptomatic remission achieved in 46% at both timepoints.
– Safety signals were consistent with expectations: three serious adverse events in 26 participants and common adverse events including COVID-19, injection site pain, and headache.
Background and disease burden
Ulcerative colitis (UC) diagnosed in childhood or adolescence can be aggressive, with substantial impacts on growth, development, psychosocial functioning, and health-care utilization. Therapeutic options for moderately-to-severely active paediatric UC include corticosteroids, immunomodulators, anti–tumour necrosis factor agents, vedolizumab, ustekinumab, and small-molecule JAK inhibitors; however, a meaningful proportion of children exhibit primary nonresponse, secondary loss of response, or intolerance to available agents. There is therefore an ongoing need for effective and well-tolerated therapies tailored to paediatric physiology and disease course.
Mirikizumab is a humanized IgG4 monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), thereby reducing Th17-pathway signalling implicated in mucosal inflammation. Mirikizumab has demonstrated efficacy and acceptable safety in adult trials for ulcerative colitis and Crohn’s disease. The SHINE-1 study was designed to evaluate pharmacokinetics, efficacy, and safety of mirikizumab in children and adolescents with moderately-to-severely active UC.
Study design and methods
SHINE-1 was a 52-week, multicentre, open-label, non-randomised phase 2 trial conducted at 19 sites in Canada, Israel, Japan, South Korea, and the United States (ClinicalTrials.gov NCT04004611). Eligible participants were aged 2 to <18 years with moderately-to-severely active UC and an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, biologics, or JAK inhibitors.
Induction therapy comprised intravenous mirikizumab given at weeks 0, 4, and 8. Participants ≤40 kg received either 5 mg/kg or 10 mg/kg; those >40 kg received a flat 300 mg dose. Clinical response was assessed using the modified Mayo score (mMS) and the Pediatric Ulcerative Colitis Activity Index (PUCAI). Responders at week 12 transitioned to fixed-dose subcutaneous maintenance injections every 4 weeks through week 48, dosed by weight bands (50 mg for ≤20 kg, 100 mg for >20–≤40 kg, 200 mg for >40 kg). Nonresponders at week 12 received three additional IV induction doses before continuing subcutaneous maintenance.
The primary endpoint (pharmacokinetics) was reported separately. The present analysis reports secondary efficacy and safety outcomes in the modified intention-to-treat and safety populations (participants receiving ≥1 dose).
Key findings
Population: Between May 18, 2020 and March 15, 2023, 26 participants were enrolled. Mean age was 11.8 years (SD 3.4), mean weight 40.5 kg (SD 16.0); 58% were female. Baseline disease severity was moderate-to-severe per inclusion criteria.
Induction outcomes (week 12)
By modified Mayo score (mMS):
- Clinical response: 18/26 (69.2%; 95% CI 50.0–83.5)
- Clinical remission: 10/26 (38.5%; 95% CI 22.4–57.5)
- Endoscopic remission: 14/26 (53.8%; 95% CI 35.5–71.2)
- Histologic–endoscopic mucosal improvement (HEMI): 4/26 (15.4%; 95% CI 6.2–33.5)
- Histologic–endoscopic mucosal remission (HEMR): 1/26 (3.8%; 95% CI 0.7–18.9)
- Symptomatic remission: 12/26 (46.2%; 95% CI 28.8–64.5)
By PUCAI: clinical response occurred in 20/26 (76.9%; 95% CI 57.9–89.0); clinical remission in 10/26 (38.5%; 95% CI 22.4–57.5).
Maintenance outcomes (week 52)
Overall persistence of benefit was observed at 52 weeks:
- mMS-based clinical response: 14/26 (53.8%; 95% CI 35.5–71.2)
- mMS-based clinical remission: 10/26 (38.5%; 95% CI 22.4–57.5)
- PUCAI-based clinical response: 14/26 (53.8%; 95% CI 35.5–71.2)
- PUCAI-based clinical remission: 13/26 (50.0%; 95% CI 32.1–67.9)
- Endoscopic remission: 10/26 (38.5%; 95% CI 22.4–57.5)
- HEMI: 9/26 (34.6%; 95% CI 19.4–53.8)
- HEMR: 9/26 (34.6%; 95% CI 19.4–53.8)
- Symptomatic remission: 12/26 (46.2%; 95% CI 28.8–64.5)
- Clinical remission without corticosteroid use or UC-related surgery for at least 12 weeks before week 52: 10/26 (38.5%; 95% CI 22.4–57.5)
Safety
Three participants (12%) experienced serious adverse events across induction and maintenance: non-infective appendicitis, worsening of ulcerative colitis (which led to study discontinuation in one participant), and pseudarthrosis. The most frequently reported adverse events were COVID-19 (6/26; 23%), injection site pain (6/26; 23%), headache (5/26; 19%), pyrexia (4/26; 15%), and viral upper respiratory tract infection (4/26; 15%). No unexpected safety signals were reported in the sample, and the overall tolerability was in line with prior adult experience with mirikizumab.
Expert commentary and interpretation
Clinical relevance: The SHINE-1 results suggest that IL-23 p19 blockade with mirikizumab can induce rapid clinical and endoscopic improvement in a paediatric population with moderately-to-severely active UC, and that a substantial proportion of initial responders maintained benefit through 52 weeks. Endoscopic remission rates at week 12 and durability at week 52 are clinically meaningful outcomes, given the association of mucosal healing with better long-term outcomes in paediatric UC.
Mechanistic plausibility: IL-23 is central to Th17-cell differentiation and maintenance, pathways implicated in mucosal immune activation in inflammatory bowel disease. Inhibiting IL-23 p19 may therefore target a pathogenic axis relevant across age groups. Pediatric immune ontogeny and medication pharmacokinetics necessitate dedicated paediatric evaluation—SHINE-1 provides important early pharmacodynamic and clinical signals.
Strengths
- Multi-national, multi-centre design with rigorous endoscopic and histologic assessments.
- Weight-based dosing strategy that mirrors paediatric pharmacokinetic considerations.
- Comprehensive 52‑week follow-up including endoscopic endpoints and steroid‑free remission data.
Limitations and cautions
- Open-label, non-randomised design without a placebo or active comparator limits causal inference and increases susceptibility to observer and selection bias.
- Small sample size (n=26) restricts precision of estimates and limits detection of less common adverse events.
- Heterogeneity of prior therapies and dosing cohorts may complicate interpretation of subgroup effects.
- Primary pharmacokinetic data were reported separately; integrated interpretation requires cross-referencing those results.
- The trial period overlapped the COVID-19 pandemic, which may contribute to infection event reporting and influence healthcare-seeking behavior.
Implications for practice and future research
While SHINE-1 provides encouraging efficacy and safety signals for mirikizumab in paediatric UC, definitive practice change requires confirmatory randomized, placebo-controlled phase 3 trials with larger and more diverse populations. Important future questions include comparative effectiveness versus available biologics (anti–TNF, vedolizumab, ustekinumab), optimal positioning in treatment algorithms (first-line biologic versus later-line), long-term safety—especially infection, malignancy, growth and development outcomes—and immunogenicity in children. Pharmacokinetic/pharmacodynamic bridging to adults appears feasible, but maturation-dependent dosing optimization may be refined with larger datasets.
Clinicians should interpret these findings as preliminary evidence that supports further evaluation. In clinical care today, mirikizumab should remain within investigational or regulatory pathways; its use outside of trials should follow local approvals and careful risk–benefit assessment.
Conclusion
SHINE-1 demonstrates that mirikizumab produced meaningful induction and sustained clinical and endoscopic responses in a small cohort of paediatric participants with moderately-to-severely active ulcerative colitis, with an acceptable safety profile over 52 weeks. The data support progression to larger, randomized trials to establish efficacy, comparative effectiveness, and long-term safety in the paediatric population.
Funding and registration
The study was funded by Eli Lilly and Company. Trial registration: ClinicalTrials.gov NCT04004611.
References
Kaplan JL, Bousvaros A, Turner D, Dubinsky M, Larkin A, Johns J, Otani Y, Crandall W, Komocsar WJ, Hyams JS. 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. 2025 Nov 18:S2468-1253(25)00196-7. doi: 10.1016/S2468-1253(25)00196-7. Epub ahead of print. PMID: 41270771.
