Switching to Siponimod Safe and Tolerable

In interim analysis of the EXCHANGE study (NCT03623243), switching from another disease-modifying treatment (DMT) without washout to siponimod (Mayzent; Novartis, East Hanover, NJ) had an acceptable safety and tolerability profile. No unexpected findings occurred after switching DMTs and there was no evidence of meaningful reduction in heart rate when treated with siponimod in the overall group or subgroups in the study.

There were 113 participants total, both male and female persons age 18 to 65, and 23 participants discontinued siponimod because of adverse events (n=5), physician decision (n=1), progression of disease (n=1), and participants' choice (n=16). Of the participants, 74.1% had relapsing-remitting multiple sclerosis (MS) and 21.4% had secondary progressive multiple sclerosis (SPMS). Previous DMTs were fingolimod, glatiramer acetate, dimethyl fumarate, teriflunomide, and any interferon. In the 12 months before screening, 42% of participants had 1 or fewer relapses. The Expanded Disability Status Scale (EDSS) score at the screening for participants were ≥2 to 6.5.

The study was a 6-month prospective multicenter open-label, single arm trial. Most of the participants switched to siponimod within 24 hours of the last dose of previous DMT. Of the participants, 100 were enrolled in remote patient cohort, in which assessment and recruitment were conducted through telehealth. The target dose of the study was 2 mg siponimod and during the first 5 days of the study the dose titration started at .25 mg and increased by .25 mg on the 3rd day to the 6th day. 

The adverse events leading to participants discontinuing from the study were abnormal behavior, cognitive disorder, edema peripheral, fatigue, insomnia, nausea, pain in extremity, tremor, and vomiting. Serious adverse events reported were asthenia, MS relapse, noncardiac chest pain, pneumonia aspiration, seizure, and tubulointerstitial nephritis.