REAL WORLD EXPERIENCE WITH MIRIKIZUMAB IN THE TREATMENT OF HIGHLY REFRACTORY AND PRETREATED (INCLUDING USTEKINUMAB) ULCERATIVE COLITIS: INTERIM-ANALYSIS FROM A LARGE EUROPEAN TERTIARY CENTER POPULATION

Abstract INTRODUCTION Mirikizumab (MIRI), a monoclonal antibody targeting IL-23, was approved in Germany in May 2023 for the treatment of moderately to severely active ulcerative colitis (UC), following favorable results in clinical trials. We aimed to evaluate the effectiveness and safety of MIRI in a real-world setting, focusing on a UC-population with prior exposure to 3 or more advanced therapies including ustekinumab. Aims & Methods In October 2023, we initiated a prospective observational study, collecting clinical, biochemical, and endoscopic data from adult pat. (n = 100) with moderate to severe UC who began MIRI treatment in our tertiary referral center in Munich, Germany. The primary endpoints were clinical remission, defined as a Clinical Activity Index (CAI, Lichtiger score) < 4 at 1 yr and endoscopic remission, defined as endoscopic Mayo score ≤1 at 6-12 mo. Secondary outcomes included monthly trends in fecal calprotectin levels, CAI scores, and stool urgency (NRS) during the observation period. Steroid withdrawal and adverse events were systematically recorded. All statistical analysis was performed by SolidPulse Software in Python using pandas, scipy and statsmodels. This report presents the key results from pat. who have completed at least 6 mo of treatment and undergone control endoscopy. RESULTS To date, 90 pat. have initiated MIRI therapy as approved after being treated with 3 or more targeted therapies. Three pat. have discontinued treatment. Of these, 64 have at least reached the 6 mo follow-up. Median disease duration was 10 yrs (1–43), male sex was 50%, and median age was 42 yrs (19 to 81). At study start, 41 pat. (64%) had a Mayo endoscopy score of 2 or 3 and 23 (36%) received MIRI simultaneously with at least one other targeted therapy. 32 pat. (50%) had previously shown loss of response to ustekinumab. 24 pat. (38%) were on steroids and 21 (33%) were in remission at study start. The rates of clinical remission (CAI < 4) increased from 33% at start to 44% (p = 0.21) at 1 mo, 49% at 3 mo (p = 0.02), and 61% at 6 mo (p = 0.003; McNemar). Median urgency scores improved on the NRS from 5 (0–10) at start to 1 (0–9) at 6 mo (p < 0.0001, Wilcoxon). Median calprotectin decreased from 464 ug/g (20–2100) at start to 77 (20–2100) at 6 mo (p < 0.0001, Wilcoxon). 49% of the pat. who were not in remission at baseline remitted at 6 mo (p = 0.004; McNemar). Among 32 pat. with prior ustekinumab use, clinical remission increased from 38% at start to 56% at 6 mo (p = 0.11, McNemar). Among 30 pat. who completed at least 6 mo and underwent control endoscopy, endoscopic remission (Mayo 0-1) improved from 33% to 64% (p = 0.007, McNemar). CONCLUSION Mirikizumab demonstrated clinical, endoscopic and biochemical effectiveness and was well tolerated in a large real-world UC cohort of pat. with longstanding disease and multiple prior treatments including ustekinumab.