COVID-19 outcomes in fingolimod- or siponimod - treated patients: clinical trial and post marketing cases

ABSTRACT

Introduction: Understanding how immunomodulatory therapies influence COVID-19 outcomes in people living with multiple sclerosis (PlwMS) is vital to patients and physicians alike. Aims and Objective: Evaluate COVID-19 outcomes in PlwMS receiving either fingolimod or siponimod. Method(s) The Novartis clinical trial (CT) and safety databases were reviewed to identify confirmed (CT confirmed if patient is SARS COV-2 positive;post-marketing [PM] considered as reported) or suspected cases of COVID-19 in PlwMS receiving either fingolimod or siponimod (CT cut-off fingolimod 04-Aug- 2021, siponimod 29-Oct-2021;PM cut-off fingolimod 28-Feb- 2022, siponimod 25-Mar-2022). Result(s) For fingolimod, there were 1054 cases comprising of 45 suspected (PM=45) and 1009 confirmed cases (CT=9;PM=1,000) of COVID-19 (mean age in years 17 [CT], 43 [PM];female 71% [715/1009;CT=4, PM=711];male 25% [254/1009;CT=5, PM=249] and not reported 4% [40/1009;PM=40]). Of these, 35% (358/1009;CT=8, PM=349) were from Europe, 30% (305/1009;PM=305) from the US and 34% (347/1009;CT=1, PM=346) from the rest of the world (ROW). Hospitalisation was required for 13% of patients (130/1009;PM=130);1% (13/1009;PM=13) had a fatal outcome;and 43% (437/1009;CT=9, PM=428) recovered or were recovering at the most recent follow-up. For siponimod there were 321 cases comprising of 6 suspected (CT=1;PM=5) and 315 confirmed cases (CT=53;PM=262) of COVID-19 (mean age in years 49 [CT], 53 [PM];female 68% [214/315;CT=34, PM=180];male 28% [88/315;CT=19, PM=69] and not reported 4% [13/315;PM=13]). Of these, 53% (168/315;CT=6, PM=162) were from the US;30% (96/315;CT=46, PM=50) from Europe;and 16% (51/315;CT=1, PM=50) from the ROW. Hospitalisation was required for 19% of patients (60/315;CT=15, PM=45);2% (7/315;CT=3, PM=4) had a fatal outcome;and where information was provided 42% (131/315 CT=50, PM=81) recovered or were recovering at the most recent follow-up. Conclusion(s) Available data indicates that most COVID-19 cases among PlwMS treated with fingolimod or siponimod were nonserious. Among PlwMS exposed to disease-modifying therapies (DMTs), the reported hospitalisation and mortality rates are 12.8%-21.5% and 1.62%-3.5%, respectively (Reder et al 2021;Sormani et al 2022). Thus, hospitalisation and fatality rates with siponimod and fingolimod in these series of Novartis reported cases were similar to those observed in PlwMS on other DMTs.