P544 Histological remission following ozanimod treatment is associated with concurrent clinical remission and endoscopic mucosal healing: Results from the TOUCHSTONE study. (16th January 2018)

• Record Type: Journal Article
• Authors: Feagan, B G; Sandborn, W J; D'Haens, G; Pai, R K; Hanauer, S B; Wolf, D C; Vermeire, S; Ghosh, S; Levesque, B G; Shan, K; Aranda, R; Liu, W J; Olson, A
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 1(2018:Jan.)Supplement 1
• Page Start: S381
• Page End: S381
• Publication Date: 2018-01-16
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjx180.671
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: TOUCHSTONE was a randomised, double-blind, placebo-controlled phase 2 trial of ozanimod 1 and 0.5 mg vs. placebo in patients with moderate-to-severe ulcerative colitis (UC). In this trial, a significantly greater proportion of patients on ozanimod 1 mg vs. placebo achieved clinical remission, response, and endoscopic mucosal healing based on Mayo score at Weeks 8 and 32. We also assessed whether ozanimod leads to histologic improvement and healing. Methods: 197 patients were randomised (1: 1: 1) to ozanimod 1 mg ( n = 67), 0.5 mg ( n = 65), or placebo ( n = 65), with 103 (52.3%) entering a maintenance period and 91 (88.3%) completing. Baseline, Weeks 8 and 32 biopsies were scored by a central pathologist blinded to treatment and visit. Histologic improvement was based on the change from baseline in Geboes score (range 0–22). Histologic remission was defined as Geboes <2. Endoscopic remission was defined as endoscopic score ≤1. Clinical remission was defined as total Mayo score ≤2, with no subscore >1. Results: Baseline mean Geboes score was similar in the 1 mg, 0.5 mg, and placebo groups (12.92, 14.36, and 13.94, respectively). Histologic improvement as measured by mean change in Geboes score was greater in the 1 mg group than placebo at both Week 8 (−4.37 vs. −2.20, p = 0.0345) and Week 32 (−5.50 vs. 2.24, p = 0.0033). The 0.5 mg group showed the same trend but the difference vs. placebo was not significant at Week 8 (−3.31 vs. −2.20, p = 0.5885) or Week 32 (−4.31 vs. −2.24, p = 0.2448). Histologic remission (Geboes <2) at Week 8 occurred in 15 of 67 (22.4%) for 1 mg ( p = 0.0705 vs. placebo), 9 of 65 (13.8%) for 0.5 mg ( p = 0.6294, vs. placebo) and 7 of 65 (10.8%) for placebo, and for Week 32 in 21 of 67 (31.3%) for 1 mg ( p = 0.0006, vs. placebo), 15 of 65 (23.1%) for 0.5 mg ( p = 0.0164 vs. placebo), and 5 of 65 (7.7%) for placebo. In patients treated with ozanimod, endoscopic remission and clinical remission were highly concordant with histologic remission (87.1% and 82.6%, respectively) at Week 32. Concordance between endoscopic remission and histologic remission at Week 32 was high in both the 1 and 0.5 mg groups (83.6% and 90.8%, respectively). Across ozanimod patients, concordance between histologic remission and normalised Physician Global Assessment (PGA = 0) was 75.8%, the absence of diarrhoea (SFS = 0) was 73.5%, and rectal bleeding (RBS = 0) was 65.2%. Conclusions: Ozanimod was effective in the induction of clinical, endoscopic, and histologic remission at Week 32 in patients with moderate-to-severe UC. Histologic remission at Week 32 following treatment with ozanimod is highly concordant with endoscopic and clinical remission.