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Mirikizumab successfully resolves active histologic inflammation in UC

Presented by
Prof. Fernando Magro, CHU de São João, Portugal
UEGW 2022
Phase 2, LUCENT 2

Significantly greater rates of histologic improvement, histologic remission, histologic-endoscopic mucosal improvement, and histologic-endoscopic mucosal remission were observed in patients with ulcerative colitis (UC) treated with mirikizumab versus placebo at week 12. Moreover, efficacy was consistently demonstrated in patients regardless of prior biologic or tofacitinib exposure/failure during induction and maintenance treatment with mirikizumab.

Mirikizumab is a monoclonal antibody against IL-23, an IgG4 antibody binding to the p19 subunit of IL-23. Prof. Fernando Magro (CHU de São João, Portugal) investigated whether mirikizumab can resolve active histologic inflammation [1].

Histologic and combined histologic and endoscopic endpoints in patients with moderately to severely active UC who receive mirikizumab treatment through week 52 were assessed. Data derived from the phase 3 LUCENT 1 study (NCT03518086) was used to evaluate the safety and efficacy of mirikizumab compared with placebo over a 12-week induction period. Participants who demonstrated a clinical response to mirikizumab in this trial at week 12 (n=544) were randomised 2:1 into a double-blind maintenance period, the LUCENT 2 trial (NCT03524092). In this trial, participants received 200 mg mirikizumab intravenously (n=365) or placebo (n=179) every 4 weeks, up to week 40.

Both at week 12 and 52, greater proportions of participants treated with mirikizumab achieved histologic improvement (Geboes ≤3.1), histologic remission (Geboes ≤2B.0), histologic-endoscopic mucosal improvement (Mayo endoscopic subscore [ES]=0/1 excluding friability + Geboes ≤3.1), and histologic-endoscopic mucosal remission (ES=0/1 excluding friability + Geboes ≤2B.0) compared with placebo (P<0.001 for each comparison). At week 40, a significantly greater proportion of participants treated with the IL-23 inhibitor achieved resolution of active histologic inflammation with absence of neutrophils in mucosa (as assessed by a histologic remission treatment difference of 22.5% with P<0.001 and a histologic-endoscopic mucosal remission treatment difference of 19.9% with a P<0.001).

The authors concluded that incorporation of histology and histologic-endoscopic outcomes as a potential treatment target could enhance the current treatment strategies in UC.

  1. Magro F, et al. Efficacy of mirikizumab in resolving active histologic inflammation in ulcerative colitis in LUCENT-1 induction and LUCENT-2 maintenance trials. MP245, UEG Week 2022, 8–11 October, Vienna, Austria.

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