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

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.