Abstract
Objectives EXCHANGE is a 6-month, open-label, single-arm trial of conversion to siponimod in patients with MS. Here we report interim analyses evaluating safety and tolerability of converting to siponimod from other disease-modifying therapies (DMTs).
Methods Analysis included patients aged 18–65 years with advancing forms of RMS and on continuous oral/injectable DMTs for ≥3 months at time of consent. Patients previously on teriflunomide required 11–14 days accelerated washout. Those converting from fingolimod immediately switched to siponimod 2mg, with no dose-titration. All other patients were titrated from 0.25 to 2mg over 6 days. Primary endpoint was incidence of adverse events (AEs) possibly related to siponimod treatment.
Results 163 patients (74.2% female; mean age 46.6 years; mean baseline EDSS score 3.9) were eligible for safety analysis. Most common prior DMTs were oral and injection therapies: 30.7% fingolimod, 27.6% glatiramer acetate/IFNβ, 20.9% dimethyl fumarate, and 17.2% teriflunomide. In safety analysis, 31.3% of patients reported ≥1 AE possibly related to siponimod treatment. Most common AEs by preferred term were headache(8.0%), dizziness(4.3%), nausea(3.7%), bradycardia(3.1%), and fatigue(3.1%). There was no decrease in heart rate at 6 hours post 1st dose from baseline in the overall or any of the prior DMT groups. In the subgroup of fingolimod patients (n=7) who were switched to siponimod without dose titration, mean heart rate (SD) was 73.1 bpm (18.1) at 6 hours post 1st dose vs 68.4 bpm (10.8) at baseline.
Conclusions Immediate conversion from other DMTs to siponimod had an acceptable safety and tolerability profile, with no unexpected findings.
