Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes

Journal of Crohn's & Colitis · 11 authors, 15 centres

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TL;DR

This pooled analysis of two randomized controlled trials (LUCENT-1 induction and LUCENT-2 maintenance) found that mirikizumab significantly improved histological and endoscopic outcomes in patients with moderately-to-severely active ulcerative colitis compared to placebo. Early resolution of inflammation was associated with better long-term clinical outcomes.

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This analysis pooled data from two randomized, placebo-controlled trials evaluating mirikizumab in ulcerative colitis. LUCENT-1 was a 12-week induction study (N=1162), and LUCENT-2 was a 40-week maintenance study (N=544) in patients who responded to induction. The primary focus was on histological and endoscopic endpoints. At Week 12, significantly more patients on mirikizumab achieved histological improvement, histological remission, endoscopic remission, and the composite endpoints histological-endoscopic mucosal improvement (HEMI) and histological-endoscopic mucosal remission (HEMR) versus placebo (p < 0.001). Similar significant improvements were seen at Week 40 in the maintenance phase. The treatment effect was generally consistent regardless of prior biologic failure. Predictors of response included lower baseline disease activity and no prior biologic failure. Notably, achieving histological and endoscopic remission at Week 12 was associated with better clinical outcomes at Week 40, such as corticosteroid-free remission and symptomatic remission.

STUDY TYPE

RCT

SPECIALTY

gastroenterology

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ORIGINAL PAPER

PMC10588772

Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes

Journal of Crohn's & Colitis

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ABSTRACT

Abstract Background and Aims To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC]. Methods Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR. Results Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [ p <0.001], irrespective of prior biologic/tofacitinib failure [ p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [ p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [ p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [ p <0.05]; ER at W12 was associated with clinical remission [CR] [ p <0.05] and corticosteroid-free remission [CSFR] at W40 [ p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [ p <0.05]. Conclusions Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086 ; LUCENT-2, NCT03524092 .

CITATION EXPORT

Fernando Magro, Rish K Pai, Taku Kobayashi et al.. Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. Journal of Crohn's & Colitis. (2023). https://doi.org/10.1093/ecco-jcc/jjad050

AUTHORS

11 · 15 CENTRES

Fernando Magro, Rish K Pai, Taku Kobayashi, Vipul Jairath, Florian Rieder, Isabel Redondo, Trevor Lissoos, Nathan Morris, Mingyang Shan, Meekyong Park, Laurent Peyrin-Biroulet

Department of Gastroenterology, University Hospital São João, Porto, Portugal
CINTESIS@RISE - Health Research Network, Faculty of Medicine, University of Porto, Porto, Portugal
Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA
Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
Alimentiv Inc., London, ON, Canada
Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
Eli Lilly Portugal, Produtos Farmacêuticos Lda., Lisbon, Portugal
Eli Lilly and Company, Indianapolis, IN, USA
Eli Lilly and Company, Indianapolis, IN, USA
Eli Lilly and Company, Indianapolis, IN, USA
TechData Service Company LLC, Philadelphia, PA, USA
University of Lorraine, Inserm, NGERE, Nancy, and Groupe Hospitalier Privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France