IL-23 is a cytokine that has been implicated in mucosal inflammation in UC. Previous research has shown that absence of intra-epithelial neutrophils is recommended as a minimum requirement for defining histological remission1. Prof. Fernando Magro (CHU de São João, Portugal) and his team investigated whether mirikizumab, an IgG4 antibody binding to the p19 subunit of IL-23, can resolve active histologic inflammation in patients with moderately-to-severely active UC through week 522.
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. Patients who demonstrated a clinical response to mirikizumab in this trial at week 12 (n=544) were randomized 2:1 into a double-blind, maintenance period, the LUCENT 2 trial (NCT03524092). In this trial, participants received 200 mg mirikizumab (n=365) or placebo (n=179) every 4 weeks up to week 40.
Both at week 12 and 40, 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 higher proportion of patients treated with the IL-23 inhibitor achieved resolution of active histologic inflammation with absence of neutrophils in mucosa.
The authors conclude that incorporation of histology and histologic-endoscopic outcomes as a potential treatment target could enhance the current treatment strategies in UC.