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. Conflict of interest: Prof. Gutiérrez Casbas, Ana: Consultant for: AbbVie, Amgen, Celltrion, Lilly, Ferring, Galapagos, Fresenius Kabi, J & J, Pfizer, Sandoz, Takeda. Speaker’s Fees for: AbbVie, Amgen, Bristol-Myers Squibb, Lilly, Ferring, Fresenius Kabi, Glaxo-Smith Kline, J & J, Pfizer, Roche, Sandoz, Shire, Takeda. Advisory Boards for: AbbVie, Amgen, Biogen, Lilly, Ferring, Fresenius Kabi, Glaxo-Smith Kline, Janssen, Merck, Pfizer, Sandoz, Takeda. Barreiro-de Acosta, Manuel: MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, Diasorin, Oncostellae and SunRock. De Castro Parga, Maria Luisa: No conflict of interest Madero Velázquez, Lucía: No conflict of interest Rodríguez, Cristina: No conflict of interest Aguas, Peris: Mariam Aguas has served as a speaker or has received research or education funding or advisory fees from AbbVie, Abbott, Alfasigma, Faes, Dr. Falk, Ferring, Kern Pharma, Janssen, Lilly, Norgine and STADA. Huguet, José María: Jose M. Huguet has served as a speaker and consultant for or has received research funding from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring, Sandoz, Tillotts Pharma, Dr. Falk Pharma and Faes Farma. Diz Lois Palomares, Maria Teresa: No conflict of interest Bermejo San Jose, Fernando: No conflict of interest Fernandez Clotet, Agnes: No conflict of interest Ber, Yolanda: No conflict of interest Antón, María Rosario: No conflict of interest Olivares, Sonsoles: No conflict of interest Sierra Ausín, Mónica: Mónica Sierra-Ausín has served as speaker or has received research or education funding or advisory fees from AbbVie, Ferring, Janssen, Lilly, Pfizer, Takeda and Pfizer. Robles-Osa, Daniel: No conflict of interest Moralejo Lozano, Óscar: No conflict of interest Martin Arranz, Maria Dolores: María Dolores Martín-Arranz has served as a speaker or has received research or education funding or advisory fees from AbbVie, Pfizer, Takeda, Janssen, TillottsPharma, Lilly and Galapagos. Cotaina, Andrea: No conflict of interest Fueyo, Pablo: IM-J has served as a speaker, a consultant and advisory member for or has received research funding from AbbVie, Amgen, Chiesi, Dr. Falk Pharma, Faes Farma, Ferring, Fresenius, Galapagos, Gebro Pharma, Janssen, Kern Pharma, Lilly, MSD, Otsuka Pharmaceutical, Pfizer, Sandoz, Shire Pharmaceuticals, Takeda, Tillotts Pharma and Vifor Pharma. Ramirez Palanca, Jose Joaquin: No conflict of interest García-Bosch, Orlando: No conflict of interest Trapero Martinez, Ana María: No conflict of interest Brunet, Eduard: No conflict of interest Varela Trastoy, Pilar: No conflict of interest De Francisco Garcia, Ruth Maria: RDF has received support for congress and conference attendance and education funding from Pfizer, AbbVie, Tillots, Takeda, Ferring and Janssen. Ceballos Santos, Daniel: DC has served as speaker, consultant and advisory board or has received research funding from MSD, AbbVie, Janssen, Takeda, Biogen, Lilly, Sandoz, Ferring, Adacyte, Faes Farma, Kern Pharma, Pfizer, Vifor Pharma, Chiesi, and Tillotts. Ponferrada Diaz, Angel: AP has served as a speaker or has received research or education funding or advisory fees from Lilly, Takeda, J and J, FAES Pharma, Falk, AbbVie, Kern Pharma and Alfasigma. Gómez Espín, Rosa María: No conflict of interest Rodriguez Moranta, Francisco: FR-M has served as a speaker and has received research or education funding or advisory fees from Lilly, Takeda, J&J, FAES Pharma, Falk, AbbVie, Pfizer, Tyllots, Ferring and Kern Pharma. Zabana, Yamile: YZ has received support for conference attendance, speaker fees, research support and consulting fees from: AbbVie, Adacyte Therapeutics, Alfa-Sigma, Amgen, Boehringer Ingelheim, Dr Falk Pharma, FAES Pharma, Fresenius Kabi, Ferring, Galapagos, J and J, Kern Pharma, Lilly, MSD, Pfizer, Sanofi, Sandoz, Takeda and Tillots Pharma. Elorza, Ainara: No conflict of interest Manceñido Marcos, Noemí: NMM has served as a speaker and consultant for or received financial support for educational activities from Janssen, Abbvie,Pfizer, Takeda, Ferring, Faes Farma, Dr. Falk Pharma, and TillotsPharma Sampedro Gonzalez, Manuela: No conflict of interest Betoré Glaría, Elena: No conflict of interest Calvo, María: No conflict of interest Ferrer, Juan: No conflict of interest Marcos Carrasco, Natalia: No conflict of interest Mena Sánchez, Raquel: No conflict of interest Domènech Moral, Eugeni: ED has served as a speaker or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Ferring, Galapagos, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Samsung, Takeda and Tillots. Rodríguez-Lago, Iago: No conflict of interest
Casbas et al. (Thu,) studied this question.