P469 Effect of mirikizumab on clinical and endoscopic outcomes based on prior advanced therapy failure in patients with moderately to severely active ulcerative colitis
Navabi, S.(1)*;D’Haens, G.(2);Samaan, K.H.(3);Li, X.(3);Arora, V.(3);Redondo, I.(3);Danese, S.(4);
(1)Rutgers New Jersey Medical School, Gastroenterology- Hepatolgy and Obesity Medicine, Newark- NJ, United States;(2)Amsterdam University Medical Centers, Gastroenterology, Amsterdam, The Netherlands;(3)Eli Lilly and Company, Immunology, Indianapolis, United States;(4)IRCCS San Raffaele Scientific Institute, Gastroenterology and Gastrointestinal Endoscopy Unit, Milano, Italy;
Background
In Phase 3 induction (LUCENT-1) and maintenance (LUCENT-2) studies, mirikizumab (miri), was well-tolerated and efficacious in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response, loss of response or intolerance to conventional or advanced therapy. This analysis evaluated clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy based on number and types of prior targeted immune modulator (TIMs) failures, where TIMs include biologics (anti-TNFs, vedolizumab (VDZ)) and tofacitinib.
Methods
Patients were randomized at induction baseline to receive 3 intravenous doses of 300mg miri or PBO every 4 weeks (Q4W). Responders to miri induction at Week 12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W40 (52 weeks of continuous therapy). Endpoints evaluated were clinical remission, clinical response, symptomatic remission, and endoscopic remission at Week 12 of LUCENT-1, and clinical remission, corticosteroid (CS)-free remission, endoscopic remission, and histologic-endoscopic mucosal remission (HEMR) at Week 40 of LUCENT-2. Efficacy in the subgroup of patients who failed 0, 1, ≥2 prior TIMs, anti-TNFs, VDZ, or both anti-TNF and either VDZ or tofacitinib (anti-TNF+1) were assessed. There were not enough patients with prior tofacitinib failure alone for statistical significance analysis.
Results
At LUCENT-1 baseline, 58.8%, 21.1%, and 20.2% of patients failed 0, 1, and ≥ 2 prior TIMs, respectively. 36.3% failed anti-TNFs, 18.8% failed vedolizumab (VDZ), and 15.2% failed an anti-TNF +1 other TIM. At Week 12 of LUCENT-1 and Week 40 of LUCENT-2, a greater proportion of miri-treated patients achieved efficacy endpoints compared with placebo for all subgroups (Table 1). The treatment differences [95% CI] were significant for all subgroup analyses except for some subgroups from two endpoints: clinical remission at Week 12 of induction and HEMR at week 40 of maintenance (Figure 1). Three subgroups in the Week 12 clinical remission analysis did not achieve significant treatment differences: 1 prior TIM failure (6.5% [-2.9%, 15.8%]), ≥2 prior TIM failures (7.6% [-0.3%, 15.5%]), and anti-TNF failure (6.4% [-0.6%, 13.4%]). For the HEMR endpoint all subgroups achieved significant treatment differences except for the 1 prior TIM failure subgroup (15.3% [-1%, 31.6%]).
Conclusion
Regardless of the number and types of failed prior advanced therapies, mirikizumab is efficacious for both induction and maintenance therapy in patients with moderately to severely active UC.
