Background & aims: We evaluated the ability of ustekinumab, a monoclonal antibody against the p40 subunit of interleukins 12 and 23, to induce endoscopic healing in patients with moderate to severe Crohn's disease (CD).
Methods: We performed an endoscopy substudy of 334 patients with moderate to severe CD participating in 3 randomized controlled phase 3 studies to determine the safety and efficacy of ustekinumab induction and maintenance therapy. All patients underwent colonoscopy at baseline and week 8 of the induction studies and at week 44 of the maintenance study; all colonoscopies were assessed by a blinded central reader. During the induction studies, patients were randomly assigned to groups given intravenous ustekinumab (130 mg or 6 mg/kg) or placebo. At the baseline time point of the maintenance study (week 8 of the induction studies), patients with a clinical response to ustekinumab were randomly assigned to groups given subcutaneous ustekinumab (90 mg every 12 weeks or 8 weeks) or placebo. Additional maintenance analysis populations were patients who did not respond to ustekinumab or placebo during the induction studies, and patients who responded to placebo during the induction studies; we performed a post-hoc pooled analysis of randomly assigned and non-randomly assigned patients of the maintenance study. We analyzed data from patients with an ulcer in at least 1 segment at baseline of the induction studies. The primary end point was change in the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD), from baseline, at week 8. We also assessed the efficacy of maintenance therapy.
Results: Patients given ustekinumab had a greater reduction in SES-CD from the induction baseline time point until week 8 than placebo (reduction of 2.8 in patients given ustekinumab vs a reduction of 0.7 points in patients given placebo; P = .012). Results were similar among patients in different induction studies and patients given different doses of ustekinumab. At week 44, reductions in the SES-CD from the induction baseline were greater in patients given ustekinumab (for combined groups, a reduction of 2.5; P = .176 and for every 8 weeks, a reduction of 3.1; P = .107) than patients given placebo (reduction of 1.9 points). Maintenance results were similar for the larger pooled post-hoc analysis.
Conclusions: In an analysis of data from 3 trials of patients with moderate to severe CD, ustekinumab (intravenous induction and subcutaneous maintenance) reduces SES-CD compared with placebo. We observed significant reductions in endoscopic disease activity at week 8 of induction therapy with ustekinumab. (ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355).
Keywords: Clinically Important Improvement; IM-UNITI; Mucosal Ulcers; UNITI.
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