Abstract: Safety of Concurrent Administration of Ozanimod and Serotonergic Antidepressants in Patients with Relapsing Multiple Sclerosis (2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

DMT57
Safety of Concurrent Administration of Ozanimod and Serotonergic Antidepressants in Patients with Relapsing Multiple Sclerosis

Tuesday, October 26, 2021

Exhibit Hall (Rosen Shingle Creek)

Robert T. Naismith, MD , Washington University School of Medicine, St. Louis, MO

Jeffrey A Cohen, MD , Cleveland Clinic Mellen Center, Cleveland, OH

Amit Bar-Or, MD , Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy

Krzysztof Selmaj, MD , Center for Neurology, Lodz, Poland

Hans-Peter Hartung, M.D. , Department of Neurology, UKD, Center of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Dusseldorf, Germany

James K. Sheffield, MD, MBA, MS , Bristol Myers Squibb, Princeton, NJ

Neil Minton, MD FFPM , Bristol Myers Squibb, Princeton, NJ

Marc Gleichmann, MD , Bristol Myers Squibb, Princeton, NJ

Hongjuan Liu, MD , Bristol Myers Squibb, Princeton, NJ

Jon V Riolo, PhD , Bristol Myers Squibb, Princeton, NJ

Diego Silva, MD , Bristol Myers Squibb, Princeton, NJ

Bruce A.C. Cree, MD, PhD, MAS , UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA

Background:

Ozanimod is approved in the US for the treatment of adults with relapsing multiple sclerosis (RMS) and in the EU and Canada for the treatment of adults with relapsing-remitting MS. Ozanimod’s major active metabolites are inhibitors of monoamine oxidase (MAO) B in vitro (but not MAO A); the clinical relevance is unknown. MAO inhibitors block oxidative deamination of monoamine transmitters, including serotonin. Therefore, there is concern that coadministration of ozanimod with drugs that can increase serotonin (eg, selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs]) could potentially lead to serotonin syndrome.

Objectives:

To evaluate the incidence of serotonin syndrome and potentially related adverse events (AEs), and hypertension during concomitant SSRI/SNRI use in an ongoing open-label extension study of ozanimod (DAYBREAK; NCT02576717).

Methods:

Participants with RMS who entered DAYBREAK received oral ozanimod 0.92 mg/d. SSRI/SNRI use was allowed during DAYBREAK. A narrow MedDRA search of the AE terms serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant, supplemented with a broader MedDRA search of AE terms potentially associated with serotonin syndrome and hypertension was conducted. The percentage of participants with AEs matching terms in the narrow and broad MedDRA searches was determined. Participants were analyzed by concurrent SSRI/SNRI use when AEs occurred. This analysis (data cutoff December 20, 2019) was limited to participants who entered DAYBREAK from two phase 3 trials.

Results:

Of 2256 participants who entered DAYBREAK and received ≥1 ozanimod dose, 223 (9.9%) used an SSRI/SNRI during DAYBREAK. Mean age was 37.3 years and mean time since MS symptom onset was 6.8 years at DAYBREAK entry; the majority were female (66.5%) and white (99.4%). At data cutoff, mean ozanimod exposure was 34.9 months. No participant had AEs matching the narrow search terms. Participants with at least 1 AE matching the broad search criteria were balanced in those on (12.1%) and not on (12.4%) SSRIs/SNRIs. Serotonin syndrome–related AEs (eg, tachycardia, nausea) were seen in ≤1% of participants in both groups. The incidence of hypertension during ozanimod and SSRI/SNRI use (4.5%) was comparable to those not using an SSRI/SNRI (6.0%).

Conclusions:

A broad MedDRA search did not identify an increase in serotonin syndrome–related AEs or hypertension in ozanimod-treated participants with vs without concomitant SSRI/SNRI use.

DMT57 Safety of Concurrent Administration of Ozanimod and Serotonergic Antidepressants in Patients with Relapsing Multiple Sclerosis

DMT57
Safety of Concurrent Administration of Ozanimod and Serotonergic Antidepressants in Patients with Relapsing Multiple Sclerosis