Post-Approval Safety of Subcutaneous Interferon β-1a in the Treatment of Multiple Sclerosis, with Particular Reference to Respiratory Viral Infections

Background: Subcutaneous interferon β-1a (sc IFN β-1a) is a well-established disease-modifying therapy for relapsing multiple sclerosis (RMS), with an estimated cumulative exposure of 1,809,458 patient-years (to 8 Jan 2021).

Objectives: To report on the post-approval safety profile of sc IFN β-1a in patients with RMS, including COVID-19 and other respiratory viral infections.

Methods: Serious and non-serious adverse events (AEs) from post-approval spontaneous individual case safety reports are presented from February 1998 to May 2020. AE rates are shown as total number of patients. Current COVID-19 findings are summarized.

Results: A total of 525,268 AEs have been reported; 6.6% of events were serious. No new safety concern has been identified. Analysis of the most common respiratory viral infection AEs reported spontaneously (influenza [2369 cases, constituting 0.45% of all AEs], viral infection [319], H1N1 influenza [15], viral bronchitis [6], and viral upper respiratory tract infection [5]) did not reveal any abnormal trend outside the known safety profile of sc IFN β-1a; cases were typically non-serious. There was no suggestion of an increased risk of more severe respiratory viral infection or other adverse drug reactions in patients with RMS and experiencing a respiratory viral infection while being treated with sc IFN β-1a. As of 19 January 2021, the Merck KGaA safety database included 399 confirmed cases of COVID-19 in sc IFN β-1a treated RMS patients. Of these, 43 patients were hospitalized with 4 requiring mechanical ventilation. There were 9 fatalities (5 fatal COVID-19 events [COVID-19 infection as the cause of death in 3 cases; COVID-19 pneumonia as the cause of death in 1 case; and COVID-19, sepsis and bilateral pneumonia as the causes of death in 1 case] and 4 other fatalities unconfirmed for COVID-19 involvement).

Conclusions: Cumulative to 19 January 2021, there was no increased risk of COVID-19 in sc IFN β-1a treated RMS patients and the majority of cases were relatively mild, consistent with previously reported registries.