Early histologic, endoscopic, and histoendoscopic response at the end of induction therapy with mirikizumab is associated with corticosteroid-free remission (CSFR) and clinical remission (CR) in ulcerative colitis (UC) at 52 weeks, according to study results presented at Digestive Disease Week (DDW), held from May 6 to 9, 2023 in Chicago, Illinois, and virtually.
For the current study, researchers analyzed clinical outcomes from 2 phase 3 trials (LUCENT-1 and LUCENT-2; ClinicalTrials.gov Identifier: NCT03518086, NCT03524092, respectively). Researchers documented histoendoscopic responses at baseline, week 12 (induction), and week 52 (conclusion).
The study used univariable and multivariable logistic regression to identify baseline demographic and disease characteristics predictive of achieving week 12 histoendoscopic mucosal improvement (HEMI) and week 52 histoendoscopic mucosal remission (HEMR) in patients receiving treatment with mirikizumab.
HEMI and HEMR documentation involved, using endoscopic subscores (ES) = 0 or 1 for both outcomes. Researchers also set Geboes scores for HEMI and HEMR at less than or equal to 3.1 and less than or equal to 2B.0, respectively.
Researchers examined associations of histologic, endoscopic, and histoendoscopic mucosal endpoints at week 12 in the LUCENT-1 trial with clinical outcomes at week 40 in LUCENT-2. Odds ratios (ORs) were measured using data from patients (N=365) who achieved a clinical response with mirikizumab at week 12 in LUCENT-1 and were rerandomized to mirikizumab. For all outcomes, the researchers used nonresponder imputation for missing data.
Based on multivariable analyses, lower clinical baseline disease activity, no baseline immunomodulator use, no prior biologic/tofacitinib failure, and sex (female) were predictors of achieving HEMI at week 12 (P <.05). Baseline absence of corticosteroids predicted HEMR at week 52 (P <.05). Also, disease duration of 7 or more years was negatively associated with HEMR (P <.05).
Endoscopic remission at week 12 was associated with CR and CSFR at week 40 (both P <.05). Histological remission, HEMI, and HEMR at week 12 were associated with CSFR, CR, and symptomatic remission at week 40 (all P <.05).
“Early histologic, endoscopic and histoendoscopic response at the end of induction was associated with CSFR and CR at W52 [week 52],” the study authors wrote. “This is the first study with an p19–targeted anti–interleukin-23 monoclonal antibody in UC to identify baseline predictors of histoendoscopic treatment outcomes and early histoendoscopic predictors of meaningful longer-term UC outcomes.”
Magro F, Pai R, Kobayashi T, et al. Early histoendoscopic response at week 12 predicts clinical outcomes at week 52 with mirikizumab in ulcerative colitis LUCENT trials. Abstract presented at: DDW 2023; May 6 to 9, 2023; Chicago, IL. Abstract Mo1735.