Evaluate siponimod first-dose effects with concomitant SSRI use in EXPAND trial.

SSRIs, citalopram and escitalopram, are associated with prolonged QTc and torsades de pointes; transient heart rate decrease at initiation is a known effect of sphingosine 1-phosphate (S1P) receptor modulators. Siponimod, a S1P receptor modulator, is approved in the USA for RMS. First-dose observation with siponimod is only required in certain cardiac conditions but it is important to understand the cardiac effects in patients receiving concomitant SSRIs.

Analyses included data for the overall siponimod group (with or without SSRI), and subgroups of concomitant siponimod and any SSRI at first dose (Day 1), and concomitant siponimod and citalopram/escitalopram on Day 1.

In all, 1105 patients were randomized to siponimod, 167 received any SSRI on Day 1, and 85 received citalopram/escitalopram; for those with extended monitoring, most were discharged at 6 hours post-first dose (91.1%, 91.4%, and 89.6%, respectively). Day 1 after first dose, 4 patients (0.4%) in the overall siponimod group had serious AEs (SAEs), 2 (0.2%) had bradycardia, and 1 (0.1%) had second-degree atrioventricular block; no SAEs occurred in the other two subgroups. Few patients in the overall siponimod group had cardiac AEs on Day 1: 29 patients (2.6%) had bradycardia, 4 (0.4%) and 3 (0.3%) had first- and second-degree atrioventricular block, respectively, and 3 (0.3%) had prolonged QT interval. Cardiac AE incidence was low in the any SSRI subgroup: 3 patients (1.8%) had bradycardia and 3 (1.8%) had prolonged QT interval; corresponding numbers in the citalopram/escitalopram subgroup were 2 (2.4%) and 1 (1.2%). In the overall siponimod group, 3 patients (0.3%) discontinued drug due to first/second-degree atrioventricular block, or bradycardia. No patient receiving SSRIs had cardiac AE causing treatment discontinuation.

Concomitant SSRI use did not appear to affect cardiac outcomes or heart rate changes associated with siponimod treatment initiation.