To report interim results of EXCHANGE (NCT03623243), a 6-month, open-label, single-arm study evaluating safety/tolerability of converting to siponimod from other disease-modifying treatments (DMTs).

In the USA, siponimod is approved in adults for treatment of RMS, including active SPMS. Understanding washout requirements when converting from other DMTs to siponimod is important in clinical practice and should be assessed prospectively.

Analysis included patients aged 18-65 years with advancing RMS, EDSS 2.0–6.5, and on continuous oral/injectable DMTs for ≥3 months at time of consent. Patients were immediately converted to siponimod, except those previously on teriflunomide who required 11-14 days’ washout (with cholestyramine or activated charcoal). During days 1-6, siponimod was titrated from 0.25 to 2mg. Primary endpoint was drug-related adverse event (AE) incidence. About 100 patients are being enrolled in a parallel, novel virtual cohort, with telemedicine tools.

112 patients (1 in virtual arm; 70.5% female) from 42 US centers were eligible for safety analysis (33.9% ongoing; 20.5% discontinued; 45.5% completed). At screening, 74.1% (n=83) had RRMS, 21.4% (n=24) had SPMS, 3.6% (n=4) had PPMS and 0.9% (n=1) had a single demyelinating event; 42.0% (n=47) had ≥1 relapse in prior 12 months. At baseline, median age was 45.5 years, median time since MS diagnosis was 11.2 years and median EDSS score was 3.5. In the safety analysis, ≥1 drug-related AE was reported in 34.8% of patients (n=39) (95% CI: 26.2-44.5); 4.5% (n=5) had ≥1 serious AE and 5.4% (n=6) had ≥1 AE leading to drug discontinuation. In patients who had completed/discontinued the study (n=74), 40.5% (n=30) (95% CI: 29.5-52.6) had ≥1 drug-related AE. Change from baseline in heart rate to 6 hours post-first dose and AEs by prior DMT will be presented.

Conversion from oral/injectable DMTs to siponimod without washout had a good safety and tolerability profile with no unexpected findings.