PD-010 Histological Remission Induced by Ozanimod is Associated with Clinical Remission and Endoscopic Mucosal Healing: Results from the TOUCHSTONE Study. (February 2017)

• Record Type: Journal Article
• Authors: William, Sandborn; Brian, Feagan; Geert, D. 'Haens; Barrett, Levesque; Rish, Pai; Stephen, Hanauer; Douglas, Wolf; Severine, Vermeire; Subrata, Ghosh; Huiling, Li; Darryl, Penenberg; Paul, Frohna; Richard, Aranda; Allan, Olson
• Is Part Of: Inflammatory bowel diseases. Volume 23(2017)Supplement 1
• Publication Date: 2017-02
• Subjects: Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/01.MIB.0000512534.24114.89
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: TOUCHSTONE was a randomized, double-blind, placebo-controlled phase 2 trial designed to assess the efficacy and safety of ozanimod 0.5 and 1.0 mg versus placebo in patients with moderate to severe ulcerative colitis (UC). Results demonstrated that a significantly greater proportion of patients achieved clinical remission, response, and endoscopic mucosal healing based on the Mayo score at weeks 8 and 32 with ozanimod 1.0 mg. We also assessed whether ozanimod leads to histologic improvement and healing. Methods: A total of 197 patients were randomized (1:1:1) to treatment with ozanimod 1.0 mg (n = 67), ozanimod 0.5 mg (n = 65), or placebo (n = 65). Of 197 patients in the Induction Period (IP), 103 (52.3%) entered the Maintenance Period (MP) to continue at their assigned dose. Out of 103 patients that entered MP, 91 (88.3%) patients completed. The Baseline, Week 8, and Week 32 biopsies were scored by a central pathologist blinded to treatment and visit. Histologic improvement was determined by assessing the change from baseline in Geboes score (range 0–22). Histologic remission was defined as a Geboes grade <2. Results: Baseline Geboes mean score was similar in the 1.0 mg, 0.5 mg, and placebo groups (12.92, 14.36, and 13.94, respectively). Histologic improvement was greater in 1.0 mg than placebo at both Week 8 (Geboes [−4.37 versus −2.20, P = 0.0345]) and Week 32 (Geboes [−5.50 versus −2.24, P = 0.0033]). The 0.5 mg group showed a numerically greater improvement than placebo but the difference did not reach significance at either Week 8 (Geboes [−3.31 versus −2.20, P = 0.5885]) or Week 32 (Geboes [−4.31 versus −2.24, P = 0.2448]). Histologic remission (Geboes <2) at Week 8 occurred in 15/67 (22.4%) for 1.0 mg ( P = 0.0705 compared to placebo), 9/65 (13.8%) for 0.5 mg ( P = 0.6294, compared to placebo) and 7/65 (10.8%) for placebo, and for Week 32 in 21/67 (31.3%) for 1 mg ( P = 0.0006, compared to placebo), 15/65 (23.1%) for 0.5 mg ( P = 0.0164 compared to placebo), and 5/65 (7.7%) for placebo. Both endoscopic remission (scores ⩽1) and clinical remission (score ⩽2, with no subscore >1) were highly concordant with histologic remission at Week 32 in patients treated with ozanimod (87.1% and 82.6%, respectively). Concordance between endoscopic remission and histologic remission at Week 32 was high in both the 1.0 mg and 0.5 mg groups (83.6% and 90.8%, respectively). Of the patients in histologic remission treated with ozanimod, the majority were in endoscopic remission (31/36 [86.1%]). Of the patients treated with ozanimod in endoscopic remission, 31/43 (72.1%) were in histologic remission. Across the ozanimod dose groups, concordance between histologic remission and normalized Patient Global Assessment (PGA = 0) was 75.8%, absence of diarrhea (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. Clinical Trials.gov: NCT01647516.