Safety of the Concurrent Administration of Serotonergic Antidepressants and Ozanimod in Patients With Relapsing Multiple Sclerosis (P7-3.013) (2023)

<h3>Objective:</h3> 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). <h3>Background:</h3> 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). <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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). <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squib. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NervGen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abata Therapeutics. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celltrion. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Journal Watch. Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen/Actelion. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech. The institution of Dr. Bar-Or has received research support from Merck/EMD Serono. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Rewind. Krzysztof Selmaj has nothing to disclose. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology. Dr. Sheffield has received personal compensation for serving as an employee of BMS. Dr. Krakovich has received personal compensation for serving as an employee of BMS. Mr. Cheng has received personal compensation for serving as an employee of Bristol Myers Squibb. Jennifer L. Reardon has received personal compensation for serving as an employee of Bristol Myers Squibb. Dr. Riolo has received personal compensation for serving as an employee of Bristol Myers Squib. Diego Silva has received personal compensation for serving as an employee of BMS. Diego Silva has received stock or an ownership interest from BMS. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Therini. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. Dr. Cree has received publishing royalties from a publication relating to health care.