Interferon beta-1a biosimilar(Biocad Medical, Inc.)

Disease-modifying therapy (DMT) has led to added challenges in the management of people with multiple sclerosis (pwMS) during the COVID-19 era. It can reduce relapse in MS or slow down disease progression, but some DMTs can increased risk of infection. The aim of study was to evaluate risk and severity of COVID-19 in pwMS.

The examined group of pwMS were divided in group treated with IFN-β1a, group treated with ocrelizumab and untreated group. The examination included impact of age, gender, duration of MS, type of MS, vaccination status and Expanded Disability Status Scale (EDSS) on the risk and severity of COVID-19 infection. A diagnosis of COVID-19 in pwMS was confirmed by positive polymerase-chain-reaction (PCR) or antigen test.

Out of 207 pwMS, 82 patients were treated with ocrelizumab, 63 with IFN-β1a, while 62 patients were untreated pwMS. The average duration of the MS was longer in the group of patients treated with ocrelizumab than in the group treated with IFN-β1a (p < 0.05). EDSS was higher in the ocrelizumab group compared to the other two groups (p < 0.001). Untreated (more often unvaccinated) had the same COVID frequency as ocrelizumab-treated (more vaccinated, but higher EDSS). The multivariate logistic regression model indicated that administration of IFN-β1a reduces the risk of COVID-19 infection (p = 0.001, OR = 0.381, 95% CI 0.602-0.160). The use of both DMTs, driven mainly by the IFN-β1a effect, reduces the risk of moderate and severe COVID-19 (p < 0.05, OR = 0.105, 95% CI 0.011-0.968).

This study provides evidence that IFN-β1a can reduce the frequency of COVID-19 infection and that two DMTs, driven mainly by the IFN-β1a effect, do not increase the risk of moderate/severe COVID-19.

The current COVID-19 pandemic was an exceptional health situation, including for drug use. As there was no known effective drug for COVID-19 at the beginning of the pandemic, different drug candidates were proposed. In this article, we present the challenges for an academic Safety Department to manage the global safety of a European trial during the pandemic. The National Institute for Health and Medical Research (Inserm) conducted a European multicenter, open-label, randomized, controlled trial involving three repurposed and one-in development drugs (lopinavir/ritonavir, IFN-β1a, hydroxychloroquine, and remdesivir) in adults hospitalized with COVID-19. From 25 March 2020 to 29 May 2020, the Inserm Safety Department had to manage 585 Serious Adverse Events (SAEs) initial notification and 396 follow-up reports. The Inserm Safety Department's staff was mobilized to manage these SAEs and to report Expedited safety reports to the competent authorities within the legal timeframes. More than 500 queries were sent to the investigators due to a lack of or incoherent information on SAE forms. At the same time, the investigators were overwhelmed by the management of patients suffering from COVID-19 infection. These particular conditions of missing data and lack of accurate description of adverse events made evaluation of the SAEs very difficult, particularly the assessment of the causal role of each investigational medicinal product. In parallel, working difficulties were accentuated by the national lockdown, frequent IT tool dysfunctions, delayed implementation of monitoring and the absence of automatic alerts for SAE form modification. Although COVID-19 is a confounding factor per se, the delay in and quality of SAE form completion and the real-time medical analysis by the Inserm Safety Department were major issues in the quick identification of potential safety signals. To conduct a high-quality clinical trial and ensure patient safety, all stakeholders must take their roles and responsibilities.