Effects of Ustekinumab on Histologic Disease Activity in Patients with Crohn’s Disease

Abstract Background & Aims Although ustekinumab is an effective therapy for moderate to severe Crohn’s disease (CD), its effects on the microscopic manifestations of CD are unknown. Methods We evaluated the effects of ustekinumab on histologic CD activity in an analysis of data from 251 participants in phase 3 induction and maintenance studies. Two endoscopic biopsies were collected at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum (18 biopsies from each patient). Histologic activity was assessed based on global histology activity scores (GHASs). Results At week 8, the mean GHAS was significantly reduced following ustekinumab induction treatment (from 10.4±7.0 to 7.1±5.9; P P P =.0137 for every 8 weeks vs placebo and P =.3529 for every 12 weeks vs placebo in the randomized population; P =.0168 for every 8 weeks vs placebo and P =.3069 for every 12 weeks vs placebo in the pooled population). Regional and overall mean GHASs correlated with the simple endoscopic score for CD (r=0.6255, P Conclusions In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo. The largest improvements occurred in patients who received ustekinumab maintenance therapy every 8 weeks. ClinicalTrials.gov no: NCT 01369329; NCT 01369342; and NCT 01369355.