Mirikizumab beneficial in paediatric ulcerative colitis

The humanised immunoglobulin G4 monoclonal antibody mirikizumab appears to be safe and efficacious in the treatment of children with moderately to severely active ulcerative colitis, according to a phase II study.

The study included 26 paediatric patients (mean age 11.8 years, 42 percent male, mean weight 40.5 kg) with moderately –to severely active ulcerative colitis with inadequate or loss of response or intolerance to corticosteroids, immunomodulators, biologics, or JAK inhibitors.

All patients received induction doses of intravenous mirikizumab 5 or 10 mg/kg (for bodyweight ≤40 kg) or 300 mg (bodyweight >40 kg) at weeks 0, 4, and 8. Clinical response was assessed using the modified Mayo score (mMS).

Patients who achieved clinical response at week 12 entered the maintenance period and received subcutaneous doses of mirikizumab 50 mg (bodyweight ≤20 kg), 100 mg (bodyweight >20 to ≤40 kg), or 200 mg (bodyweight >40 kg) every 4 weeks through week 48. Those who showed no response, on the other hand, received three additional intravenous induction doses (10 mg/kg [bodyweight ≤40 kg] or 300 mg [bodyweight >40 kg] every 4 weeks) before continuing to subcutaneous maintenance dosing.

At week 12, clinical response by mMS occurred in 18 patients (69.2 percent), of which 10 (38.5 percent) had clinical remission, 14 (53.8 percent) had endoscopic remission, four (15.4 percent) had histologic-endoscopic mucosal improvement (HEMI), one (3.8 percent) had histologic-endoscopic mucosal remission (HEMR), and 12 (46.2 percent) had symptomatic remission.

When clinical response was assessed using the Pediatric Ulcerative Colitis Activity Index (PUCAI), response at week 12 was documented in 20 patients (76.9 percent), of which 10 (38.5 percent) achieved clinical remission.

At week 52, 14 patients (53.8 percent) had mMS-based clinical response and 10 (38.5 percent) were in mMS-based clinical remission, while 14 (53.8 percent) had a PUCAI-based clinical response and 13 (50 percent) were in PUCAI-based clinical remission. Ten patients (38.5 percent) were in endoscopic remission, nine (34.6 percent) had HEMI, nine (34.6 percent) had HEMR, and 12 (46.2 percent) had symptomatic remission. Of note, 10 patients (38.5 percent) achieved clinical remission without corticosteroid use or ulcerative colitis-related surgery for at least 12 weeks leading up to week 52.

In terms of safety, serious adverse events across induction and maintenance periods occurred in three patients (12 percent). These events included noninfective appendicitis, pseudoarthrosis, and worsening of ulcerative colitis, with the latter leading to study discontinuation. The most common adverse events were COVID-19, injection site pain, pyrexia, and viral upper respiratory tract infection.