Short-term effectiveness and safety of Mirikizumab in ulcerative colitis: real-world evidence from the ENEIDA registry of GETECCU

Abstract

Background Mirikizumab (MIRI) has shown efficacy over placebo in ulcerative colitis (UC) based on the data from the pivotal clinical trials. However, these results still need to be confirmed in clinical practice. This study aims to assess the short-term real-world effectiveness and safety of MIRI in patients with UC.

Methods All patients with UC who received MIRI and without previous colectomy included in the prospectively-maintained ENEIDA registry were included. Clinical disease activity was assessed by partial Mayo score (pMS). The primary outcome was clinical remission (defined as pMS ≤2 with no subscore >1 and no rectal bleeding) at week 8 and 12, alongside its safety profile.

Results A total of 269 patients from 44 Spanish hospitals were included (mean age of 50.6 years [SD 17], 54% male, median disease duration of 125 months [SD 94], 55% non-smokers, 58% extensive colitis. Concomitant therapy at baseline included 42% with steroids and 9% with immunosuppressants. Prior advanced therapies exposure was: 85% Anti-TNF, 62% vedolizumab, 46% ustekinumab, and 36% JAK inhibitors, with 77% exposed to 2 or more than 2 mechanisms of action (MoA).At baseline patients had a median pMS 5 (IQR, 4-6) and faecal calprotectin of 1011 ug/g (IQR, 412-2463). All but one patient started MIRI 300 mg iv every 4 weeks. Mean follow-up was 8.4 (SD 10.4) months. Clinical response and clinical remission at week 8 were 46% and 32%, respectively, and 44% and 37% at week 12.Clinical remission rate at week 12 was higher among those with prior exposure to 1 MoA vs 2 or more than 2 (61.5%, 36.8%, 26.4% respectively, p = 0.001, p = 0.001, figure 1).Previous exposure to ustekinumab was associated with a significant lower rate of clinical remission at week 12 (29.6% vs. 44.2%, p = 0.028). Faecal calprotectin and pMS significantly decreased at week 12 (400 ug/g [IQR, 127-1280], p = 0.001 and 2 [IQR, 0-4], p = 0.038).The overall cumulative hospitalization and colectomy rates were 5.2% and 2.6% respectively. MIRI was generally well tolerated, with 26 (10%) of patients reporting at least one adverse event, but only 3 of them categorized as severe.

Conclusion MIRI demonstrated its real-life effectiveness in the short-term, even in a highly-refractory cohort. Prior advanced therapy exposure to more than one MoA significantly impacts the effectiveness of MIRI during the induction. Safety was consistent with the known profile of this drug.