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. Ozanimods 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.
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).
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.
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 syndromerelated 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%).
A broad MedDRA search did not identify an increase in serotonin syndromerelated AEs or hypertension in ozanimod-treated participants with vs without concomitant SSRI/SNRI use.