Dig Dis Sci. 2024 Apr 3. doi: 10.1007/s10620-024-08391-z. Online ahead of print.

Sarah Harris ^1 2, Brian G Feagan ³, Stephen Hanauer ⁴, Severine Vermeire ⁵, Subrata Ghosh ⁶, Jim Yan ⁷, Chun Wu ⁸, Yanhua Hu ⁸, Rachel Maddux ⁸, Douglas C Wolf ⁹, Geert D'Haens ¹⁰

Author information

¹Bristol Myers Squibb, Princeton, NJ, USA. sarah.harris@bms.com.

²Bristol Myers Squibb, 3033 Science Park Rd, San Diego, CA, 92121, USA. sarah.harris@bms.com.

³Robarts Clinical Trials, Robarts Research Institute, Western University, London, ON, Canada.

⁴Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

⁵University Hospitals Leuven, Leuven, Belgium.

⁶College of Medicine and Health, APC Microbiome Ireland, University College Cork, Cork, Ireland.

⁷Laboratory Corporation of America, Durham, NC, USA.

⁸Bristol Myers Squibb, Princeton, NJ, USA.

⁹Center for Crohn's Disease & Ulcerative Colitis, Atlanta Gastroenterology Associates, Atlanta, GA, USA.

¹⁰Inflammatory Bowel Disease Center, Amsterdam University Medical Center, Amsterdam, Netherlands.

Abstract

Background: Ozanimod showed efficacy and safety in the phase 2 STEPSTONE study conducted in patients with moderately to severely active Crohn's disease.

Aims: This analysis assessed the effects of ozanimod on circulating lymphocytes in Crohn's disease.

Methods: Patients received ozanimod 0.92 mg for 12 weeks. Lymphocyte subtypes were evaluated using multicolor flow analysis on blood samples collected before treatment and on Week 12. Absolute lymphocyte count changes were analyzed by Wilcoxon signed rank tests. Disease activity changes and efficacy outcomes were evaluated at Week 12, and associations with lymphocyte subtype levels were assessed using Spearman's correlation and logistic regression.

Results: Reductions in median total T, Th, and cytotoxic T cells occurred at Week 12 (45.4%-76.8%), with reductions in most subtypes of 47.5% to 91.3% (P < 0.001). CD8⁺ terminally differentiated effector memory cells were largely unaffected (median change, - 19%; P = 0.44). Reductions in median total B cells occurred at Week 12 (76.7%), with reductions in subtypes of 71.4% to 81.7% (P < 0.001). Natural killer and monocyte cell counts were unchanged. Greater baseline levels and changes in nonswitched memory B cells were significantly associated with clinical, endoscopic, and histologic efficacy (P < 0.05, all comparisons).

Conclusions: Ozanimod reduced circulating levels of all B-cell and most T-cell subsets but not monocytes or natural killer cells. Key subsets relevant to immune surveillance were not reduced, supporting the low risk of infection and malignancy with ozanimod in chronic inflammatory diseases. Levels of nonswitched memory B cells were associated with efficacy, providing a potential marker for ozanimod response.

Trial registration: ClinicalTrials.gov: NCT02531113, EudraCT: 2015-002025-19.