Coronavirus Disease 2019

Update on Coronavirus Disease 2019 Outcomes and Vaccine Efficacy in Patients With Immune-Mediated Inflammatory Disease

Jeffrey A. Sparks; Zachary S. Wallace; Philip C. Robinson

Disclosures

Curr Opin Rheumatol. 2021;33(5):412-418. 

In This Article

Vaccine Efficacy

The quick development of well tolerated and effective COVID-19 vaccines has not only been a tremendous scientific advance during the pandemic but also raises important questions about the efficacy of vaccination in patients with immune-mediated diseases, especially those on immunomodulation. Previous studies have established that several DMARD classes may be associated with a less robust immune response to vaccines for influenza, pneumococcus and other infections.[52] Unfortunately, patients with immune-mediated inflammatory conditions and those on immunomodulation were generally excluded from the initial COVID-19 vaccination trials leaving providers and patients with little guidance on how or when to vaccinate patients on DMARDs. Several reports have not only described a potentially dampened antibody response to SARS-CoV-2 mRNA vaccines among DMARD users but also highlight that the response likely varies across DMARD classes.[53–55]

In the largest study to date, 133 adults with autoimmune diseases, including IBD (31.6%), RA (28.6%), spondyloarthritis (15%) and lupus (11%) were included.[54] Though the antibody response to two doses of SARS-CoV-2 mRNA vaccines was robust among many with autoimmune diseases, it was three-fold lower than the response observed in healthy controls. Similar reductions were observed in the neutralization activity of SARS-CoV-2 antibodies. In particular, glucocorticoid users, Janus Kinase inhibitor users, antimetabolite users and especially those with recent B-cell-depleting therapy exposure had significant reductions in antibody responses. Reductions in the antibody response among patients using TNF inhibitors were more modest.

Similar observations were made in a study of 123 patients with rheumatic diseases, including inflammatory arthritis (28%), lupus (20%) and Sjogren's syndrome (13%).[53] Though 74% of patients had a detectable antibody response, a median of 22 days after the first dose of an mRNA vaccine, antibody responses were variable across DMARD classes. For instance, while nearly all TNFi users (n = 16 of 17) and methotrexate users (n = 10 of 13) had an antibody response, rituximab (n = 2 of 6) and mycophenolate mofetil (n = 3 of 11) users less often had an antibody response. The sample size of this study was small, limiting conclusions that can be drawn, especially as the response was assessed only after the first dose.

A report from a cohort of patients with a history of solid organ transplantation on medications commonly used (e.g. glucocorticoids, azathioprine, mycophenolate) described poor vaccine efficacy after the first dose of an mRNA vaccine.[55] Notably, those on mycophenolate mofetil, mycophenolic acid or azathioprine had a particularly poor response to the vaccine with only 9% mounting an antibody response following the first dose. Caution is needed whenever interpreting these data; however, as the generalizability of these findings to those with immune-mediated conditions is unclear and the immune response was only assessed following the first dose of the mRNA vaccine series, which typically includes two doses.

Additional studies are urgently needed to better define the efficacy of mRNA and other vaccines in each DMARD class, across different vaccine classes, the durability of the antibody response, the T-cell response to vaccination in this population, and the appropriate timing of vaccination in relation to DMARD use.

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