PK, Efficacy, and Safety of Mirikizumab as Induction Therapy in Pediatric Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 2 SHINE-1 Study

Mirikizumab is a humanized antibody that binds to the p19 subunit of IL-23, a key inflammatory agent in inflammatory bowel disease.¹ The open-label, multicenter, phase 2 SHINE-1 study evaluated the pharmacokinetics, efficacy, and safety of mirikizumab in pediatric patients with moderately to severely active UC.² Eligible patients were between 2 and less than 18 years of age and weighed more than 10 kg. Patients had an established diagnosis of UC for at least 3 months before baseline and moderately to severely active UC for 14 days before baseline. Enrolled patients also had exhibited an inadequate response, loss of response, or inability to tolerate treatment with at least one corticosteroid, immunomodulator, biologic therapy, or Janus kinase inhibitor for their UC. After 12 weeks of induction therapy, patients continued open-label maintenance therapy with mirikizumab. The primary objective was to determine the pharmacokinetics of mirikizumab in the pediatric patient population and define the appropriate doses for the phase 3 study in the same patient setting.

Mirikizumab was administered every 4 weeks to 10 patients who weighed 40 kg or less at a dose of 5 mg/kg and to 5 patients who weighed 40 kg or less at a dose of 10 mg/kg. Mirikizumab at a dose of 300 mg was administered to 11 patients who weighed more than 40 kg. The overall study population of 26 patients had a mean age of 11.8 ± 3.4 years, and 42.3% were male. On the basis of both actual measurements and pharmacokinetic modeling, area under the curve, and maximum plasma concentration, exposure in the patients who received mirikizumab (10 mg/kg) was approximately 2-fold higher than the mean values in adults. In the other 2 groups of pediatric patients, the mean exposure to mirikizumab was similar to that observed in adults.

Outcomes in pediatric patients in the SHINE-1 study were comparable with or better than outcomes in adults in the LUCENT-1 trial, including clinical response by modified Mayo score (69.2% vs 63.5%), clinical remission by modified Mayo score (38.5% vs 25.6%), and endoscopic remission (53.8% vs 36.3%; Figure 5).³ On the basis of PUCAI scores, the clinical response rate was 76.9% and the clinical remission rate was 38.5%. No new safety signals arose when the pediatric population in SHINE-1 was compared with the adult population in LUCENT-1. Most treatment-emergent AEs were mild, and no serious AEs occurred during the 12-week induction period with mirikizumab.

Figure 5.

Week 12 MMS clinical response, clinical remission, and endoscopic remission rates for patients treated with mirikizumab from the LUCENT-1 and SHINE-1 trials. MMS, modified Mayo score; NRI, nonresponder imputation; PBO, placebo. Adapted from Kaplan et al. Abstract 781. Presented at: DDW 2023; May 6-9, 2023; Chicago, Illinois.²