Safety of the Concurrent Administration of Serotonergic Antidepressants and Ozanimod in Patients With Relapsing Multiple Sclerosis
Robert T. Naismith1, Jeffrey A. Cohen2, Amit Bar-Or3, Giancarlo Comi4, Krzysztof W. Selmaj5, Hans-Peter Hartung6, James K. Sheffield7, Anthony Krakovich7, Chun-Yen Cheng7, Jennifer Reardon7, Jon V. Riolo7, Diego Silva7, Bruce A. C. Cree8
1Washington University School of MedicineWashington University School of Medicine, St Louis, Missouri, 2Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, 3Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of PennsylvaniaCenter for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 4Vita-Salute San Raffaele University and Casa di Cura del Policlinico, Milan, Italy, 5Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland, 6Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf Germany; Brain and Mind Centre, University of Sydney, Australia; Department of Neurology, Medical University of Vienna, Austria; and Palacký University Olomouc, Olomouc, Czech Republic, 7Bristol Myers Squibb, Princeton, New Jersey, 8Weill Institute for Neurosciences, Department of Neurology, University of California San FranciscoWeill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California
Objective:
To evaluate the incidence of serotonin syndrome (SS) and potentially related adverse events (AEs) and hypertension during and within 6 weeks of stopping concomitant selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) use in an ongoing open-label ozanimod 0.92 mg extension trial (DAYBREAK; NCT02576717).
Background:
There is concern that coadministration of ozanimod with SSRIs or SNRIs could cause SS, as the major active metabolites of ozanimod inhibit monoamine oxidase (MAO) B, which may in turn block oxidative deamination of monoamine transmitters (eg, serotonin).
Design/Methods:
Narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (AE terms potentially associated with SS and hypertension) MedDRA v24.0 searches were performed using data from patients with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). The percentage of patients who had AEs matching the terms from each MedDRA search was determined and stratified by SSRI/SNRI use.
Results:
Of 2256 patients entering DAYBREAK and receiving ≥1 ozanimod dose, 274 (12.1%) used an SSRI/SNRI during DAYBREAK. At data cutoff, mean ozanimod exposure was 56.1 months. No patients had AEs matching the narrow search terms. The percentage of patients with ≥1 AE matching the broad search criteria was lower for those on vs off SSRIs/SNRIs (on: 13.9%, n=274; off: 17.7%, n=2032), a trend that remained similar when the 6 weeks after the end date of concomitant SSRIs/SNRI use were included in the on-SSRIs/SNRI analysis period (on: 15.7%, n=274; off: 17.6%, n=2030). The incidence of hypertension was lower for those on vs off SSRIs/SNRIs (on: 4.7%, n=274; off: 9.2%, n=2032), which remained consistent with the extended analysis period (on: 5.5%, n=274; off: 9.1%, n=2030).
Conclusions:
A broad MedDRA search did not identify an increase in SS-related AEs or hypertension with vs without concomitant SSRI/SNRI use in ozanimod-treated patients in DAYBREAK.