Concomitant Administration of Ozanimod and Serotonergic Antidepressants in Patients With Ulcerative Colitis or Relapsing Multiple Sclerosis

Miguel Regueiro; Britta Siegmund; Sara Horst; Ryan Moslin; Lorna Charles; AnnKatrin Petersen; Daniel Tatosian; Hsiuanlin Wu; Garrett Lawlor; Monika Fischer; Geert D'Haens; Jean-Frederic Colombel

doi:10.1093/ibd/izae136

Concomitant Administration of Ozanimod and Serotonergic Antidepressants in Patients With Ulcerative Colitis or Relapsing Multiple Sclerosis

Inflamm Bowel Dis. 2024 Jul 17:izae136. doi: 10.1093/ibd/izae136. Online ahead of print.

Authors

Affiliations

¹ Cleveland Clinic, Cleveland, OH, USA.
² Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Bristol Myers Squibb, Princeton, NJ, USA.
⁵ Indiana University School of Medicine, Indianapolis, IN, USA.
⁶ Academic Medical Center Amsterdam, Amsterdam, Netherlands.
⁷ Icahn School of Medicine at Mount Sinai, New York, NY, USA.

PMID: 39018016
DOI: 10.1093/ibd/izae136

Abstract

Background: Ozanimod, approved for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS), is a weak in vitro monoamine oxidase B (MAO-B) inhibitor. MAO-B inhibitors can cause serotonin accumulation with concomitant use of selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs). We evaluated the incidence of treatment-emergent adverse events (TEAEs) potentially associated with serotonin accumulation during ozanimod and concomitant SSRI/SNRI use in this post hoc analysis of pooled UC studies and the open-label extension RMS DAYBREAK.

Methods: Data for ozanimod 0.92 mg from pooled UC studies (n = 1158; cutoff: January 10, 2022) and RMS DAYBREAK (n = 2257; cutoff: February 1, 2022) were analyzed. Concomitant SSRI/SNRI use was allowed in the UC (n = 67) and RMS (n = 274) studies. A narrow Medical Dictionary for Regulatory Activities search ("serotonin syndrome," "neuroleptic malignant syndrome," and "malignant hyperthermia") and a broad search including terms potentially associated with serotonin accumulation were conducted. The percentages of patients with TEAEs in both searches were analyzed by concomitant SSRI/SNRI use when the TEAE occurred.

Results: No patients had TEAEs matching the narrow search criteria. No differences were observed in the percentages of patients with ≥1 TEAE matching the broad search regardless of SSRI/SNRI use in UC (with: 25.4% [n = 17 of 67]; without: 15.0% [n = 164 of 1091]) and RMS (with: 12.4% [n = 34 of 274]; without: 15.6% [n = 310 of 1982]) studies.

Conclusions: No evidence of increased TEAEs potentially associated with serotonin accumulation was observed with concurrent use of ozanimod and SSRIs/SNRIs.

Clinical trial registration: NCT01647516, NCT02531126, NCT02435992, NCT02576717.

Keywords: ozanimod; safety; serotonergic antidepressants; serotonin accumulation; ulcerative colitis.

Plain language summary

No evidence of increased treatment-emergent adverse effects potentially associated with serotonin accumulation was observed with concurrent use of ozanimod and serotonergic antidepressants. Our findings support the absence of clinically meaningful ozanimod monoamine oxidase B inhibition in vivo.

Associated data

ClinicalTrials.gov/NCT01647516
ClinicalTrials.gov/NCT02531126
ClinicalTrials.gov/NCT02435992
ClinicalTrials.gov/NCT02576717

Grants and funding

Bristol Myers Squibb