Humoral Responses Following SARSCoV- 2 Vaccination in Patients with Commonly Used Immunosuppressants in Neuromuscular Disorders

ABSTRACT

Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders (IMIDs) treated with specific immunosuppressants and immunomodulating agents. The objective of this study is to investigate the humoral immune response after SARS-CoV-2 vaccination in patients using immunosuppressive and immunomodulating mono- and combination therapies, focussing on frequently prescribed therapies for inflammatory neuromuscular diseases. Methods: National prospective observational cohort study in selected patients with prevalent IMIDs including neuromuscular disease, and immunosuppressive or immunomodulating monotherapy (n=1273), combination therapies (n=419), patients without immunosuppressants (n=473), and healthy controls (n=174). Anti-RBD IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses, i.e. vaccination after previous SARS-CoV-2 infection, were studied as a proxy for recall responses. Findings: Sera from 1869 participants without and 470 participants with previous SARS-CoV-2 infection were analysed. We included 168 (7 2%) patients with inflammatory neuropathies and myopathies, and 127 (5 4%) patients with myasthenia gravis. Humoral responses did not differ between disorders. Anti-CD20 therapy and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks (RR) for reaching seroconversion following standard vaccination (RR 0 32 and 0 61 respectively). The monotherapies corticosteroids, purine antagonists, methotrexate, mycophenolate mofetil and IVIg were not associated with a lower RR for reaching seroconversion (RR 0 97, 0 98, 1 01, 0 86, and 0 99, respectively). Similarly, corticosteroids combined with either methotrexate or purine antagonists was not associated with a lower RR for reaching seroconversion (RR 0 89). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments but not for anti-CD20 therapies. Most immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that, in subgroups, did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment. Interpretation: Humoral responses following vaccination are impaired by specific immunosuppressants, most relevant for neuromuscular diseases being anti-CD20 and mycophenolate mofetil combination treatments. After standard vaccination regimens most immunosuppressants show equal seroconversion to controls although antibody titres may be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate in loss of (short term) protection. Alternatively, in immunosuppressants showing poor humoral responses after standard vaccination regimens such as, a third vaccination resulted in additional seroconversion in mycophenolate mofetil combination treatments whereas the effect for anti-CD20 therapy was limited.