Multiple Sclerosis, Disease-Modifying Therapies and COVID-19: A Systematic Review on Immune Response and Vaccination Recommendations

Abstract

Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations. Data from 4417 patients suggest that MS per se do not portend a higher risk of severe COVID-19. As for the general population, advanced age, comorbidities, and higher disability significantly impact COVID-19 outcomes. Most DMTs have a negligible influence on COVID-19 incidence and outcome, while for those causing severe lymphopenia and hypogammaglobulinemia, such as anti-CD20 therapies, there might be a tendency of increased hospitalization, worse outcomes and a higher risk of re-infection. Blunted immune responses have been reported for many DMTs, with vaccination implications. Clinical evidence does not support an increased risk of MS relapse or vaccination failure, but vaccination timing needs to be individually tailored. For cladribine and alemtuzumab, it is recommended to wait 3–6 months after the last cycle until vaccination. For the general anti-CD20 therapies, vaccination must be deferred toward the end of the cycle and the next dose administered at least 4–6 weeks after completing vaccination. Serological status after vaccination is highly encouraged. Growing clinical evidence and continuous surveillance are extremely important to continue guiding future treatment strategies and vaccination protocols.

Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England

“…Fingolimod also seems to prevent the production of antibodies in response to SARS-CoV-2 vaccination ( Achiron et al, 2021 ; Sormani et al, 2021 ). So far, assumptions about the impact of MS DMTs on the effectiveness of SARS-CoV-2 vaccines are based on experiences with previous vaccinations and these immunological studies rather than population-based studies ( Achiron et al, 2021 ; Apostolidis et al, 2021 ; Brill et al, 2021 ; Cabreira et al, 2021 ; Sormani et al, 2021 ). Cohort studies to assess the effectiveness of SARS-CoV-2 vaccines in patients taking MS DMTs have been set up, but it will be a while before they are concluded ( Sormani et al, 2021 ).…”

Symptoms after COVID-19 Infection in Individuals with Multiple Sclerosis in Poland

“…However, being under anti-CD20 therapies was shown to be a risk factor for hospitalization, with higher mortality in some studies; this was contradicted in others [7,21,22]. Lower humoral response after COVID-19 was observed for people treated with anti-CD20 agents and fingolimod in the work of Bigaut et al [23].We know that vaccination has to be tailored to different DMTs [24].…”

Drug Interactions for Patients with Respiratory Diseases Receiving COVID-19 Emerged Treatments

“…Fingolimod is an immunology modulator indicated as monotherapy for the treatment of patients with relapsing-remitting forms of multiple sclerosis (MS). Fingolimod has been tested for COVID-19 based on case reports regarding mild COVID-19 that mentioned continuation of the immunosuppressive drug with a full recovery without any complications, suggesting the need for further investigation regarding potential benefits from immunomodulation from fingolimod in COVID-19 patients [ 80 ]. Co-administration of fingolimod with anti-neoplastic or other immunosuppressive or immunomodulating agents should be avoided due to the enhanced risk for ADRs in immune system from PD-DDI synergisms.…”