Systematic review of risk of SARS-CoV-2 infection and severity of COVID-19 with therapies approved to treat multiple sclerosis

Abstract

There is growing concern that multiple sclerosis (MS) patients on certain therapies may be at higher risk for severe coronavirus disease 2019 (COVID-19). We conducted a systematic literature review to examine the available data on U.S. therapies approved to treat MS and the risk of SARS-CoV-2 infection or severe COVID-19 outcomes. We conducted searches in PubMed, Embase, and the WHO COVID-19 database through May 2, 2021, and retrieved articles describing clinical data on therapies approved to treat MS and the risk of infection with SARS-CoV-2 or the effects of such therapies on clinical outcomes of COVID-19. The literature search identified a total of 411 articles: 97 in PubMed, 227 in Embase, and 87 in the WHO database. After excluding duplicates and screening, we identified 15 articles of interest. We identified an additional article through a broader secondary weekly search in PubMed. Thus, ultimately, we reviewed 16 observational studies. Available data, which suggest that MS patients treated with anti-CD20 monoclonal antibodies may be at increased risk for severe COVID-19, are subject to relevant limitations. Generally, studies did not identify increased risk for COVID-19 worsening with other therapies approved to treat MS. Based on observational data, biological plausibility, novelty of the drug-event association, and public health implications in a subpopulation with potential impaired response to the COVID-19 vaccines, this safety signal merits further monitoring. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05846-3.

T cell responses to SARS-CoV-2 vaccination in people with multiple sclerosis differ between disease-modifying therapies

“…However, SARS-CoV-2 variants continue to circulate, and vulnerable groups may still be at risk of severe disease. These data show that pwMS treated with alemtuzumab, cladribine, and natalizumab have robust humoral and CD4 and CD8 T cell responses after two vaccine doses, in agreement with other studies (3, 14, 20, 22, 25). However, individuals treated with fingolimod and rituximab have strongly reduced antibody responses compared with both healthy controls and pwMS taking other DMTs.…”

“…However, some disease-modifying therapies (DMTs) can also impede an effective response to infectious diseases and vaccination (reviewed in (2)). It is unclear whether people with MS (pwMS) are more susceptible to severe COVID-19 disease in the absence of vaccination (3)(4)(5)(6); current evidence suggests that this varies depending on DMT usage, where treatment with anti-CD20 drugs presents an increased risk factor (7,8), as well as neurological disability, comorbidities, and age (6,8). It is therefore important to establish vaccine effectiveness in pwMS and whether vaccination protects against COVID-19 disease to the same extent as in the general population.…”

Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study

“…A recent analysis (May 2021) using the ocrelizumab post-marketing safety database and clinical trial data show that COVID-19 infections in patients treated with ocrelizumab were mostly mild to moderate, and risk factors known to be associated with severe disease course in the general population were associated with severity in ocrelizumab-treated ( 20 ). However, a number of real-world studies ( 21 – 24 ) suggest an increased risk of severe COVID-19 in patients with MS treated with anti-CD20 treatments although subject to potential limitations, including biases, confounding, sample size and data completeness ( 25 ). Further analyses are required to understand the risk and severity of COVID-19 in ocrelizumab treated patients.…”

SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19

“…Due to the potentially reduced risk of developing COVID-19 in pwMS treated with IFN-β or glatiramer acetate [ 43 ], the probability of death using either of these therapies is very low. This is confirmed in the systematic reviews by Sharifian-Dorche et al, 2021 and Zrzavy et al 2021, in which they show that no patient treated with IFN-β and confirmed COVID-19, died [ 44 , 45 ].…”