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P661 Early histological improvement demonstrated with oral ozanimod in patients with moderately to severely active Crohn’s disease in the STEPSTONE trial

B. G. Feagan*1, G. D'Haens2, K. Usiskin3, J. Liu3, D. Paul3, R. K. Pai4

1Robarts Clinical Trials, Western University, London, Canada, 2Academic Medical Center, Amsterdam, The Netherlands, 3Celgene Corporation, Summit, USA, 4Mayo Clinic, Scottsdale, USA

Background

Ozanimod, an oral immunomodulator that selectively targets S1P1 and S1P5, has demonstrated efficacy and safety in ulcerative colitis (UC) (Sandborn NEJM 2016) and is being evaluated in active Crohn’s disease (CD).1 The aim of the STEPSTONE study was to examine histological, endoscopic, and clinical outcomes, and safety of ozanimod in adults with CD.

Methods

STEPSTONE was an open-label uncontrolled phase 2 multi-centre trial of ozanimod for 12 weeks, followed by an extension period. Patients with active CD (Crohn’s disease Activity Index [CDAI] score 220–450, total simple endoscopic score for CD [SES-CD] ≥6 (or in isolated ileum disease SES-CD ≥4) received ozanimod 1 mg daily. Ileo-colonic endoscopic biopsies (perpendicular to the mucosal surface at the edge of the largest ulcer or in the most severely affected area in segments without ulcers) were obtained from the terminal ileum and 4 colonic segments at baseline and Weeks 12 and 52 for assessment of histological change. A post hoc analysis of histology data through Week 12 are reported here, based on an 02-October-2017 interim data cut. The Robarts Histopathology Index (RHI) is a validated, reproducible, and responsive index that incorporates four histological descriptors (severity of chronic inflammatory infiltrate, the number of lamina propria neutrophils, the number of neutrophils in the epithelium, and the severity of erosions or ulceration), each of which is objectively graded from 0 to 3 (Mosli Gut 2015).2

Results

Sixty-nine patients were enrolled. At baseline, mean age was 38 years, mean SES-CD was 13, mean CDAI score was 321, and mean RHI was 16.3. Mean CD duration was 10 years, with 54% of patients having had prior exposure to biologic therapy (ie, anti-TNF-α, vedolizumab). Table 1 presents the mean change in RHI for paired segments from baseline to Week 12 in the overall study population and in subgroups of patients with or without prior exposure to biologic therapy and by segment.

Change from baseline in robarts histopathology index (RHI) score at Week 12 – observed cases, intent-to-treat population

Through 12 weeks, most non-serious and serious adverse events appeared to be related to underlying moderate to severe CD. No new safety signals were identified.

Conclusion

Results of the STEPSTONE trial demonstrated early histological improvements among patients with moderately to severely active CD who were treated for 12 weeks with ozanimod. These improvements were seen in the patients with and without prior biologic exposure and across all segments.

References

1. Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med 2016;374:1754–62

2. Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. Gut. 2017;66:50–58.