A Systematic Review of Vaccinations in Methotrexate Users

Author(s): Sheryl Mascarenhas

With several COVID-19 vaccines now available, many questions regarding immunization within patients on immune modifying agents have been surfacing. One critical question is what effect methotrexate (MTX), a known inhibitor of antibody formation, may have on vaccine response during the pandemic. In particular, does holding methotrexate during the vaccination period have improved outcomes on vaccine response?

A systematic review was conducted of previous randomized controlled trials and clinical trials of vaccine studies for methotrexate use. Studies were limited to the adult population and to those with autoimmune rheumatic conditions. 29 studies were included for review. There was heterogeneity in vaccinations used including pneumococcal, influenza (H1N1, H3N2, and various B strains), tetanus toxoid, hepatitis A, and varicella zoster. Measurement of vaccine response was non-uniform among the studies. Methotrexate dosing in some studies was not reported, and in many studies was variable. 82.8% of the studies demonstrated methotrexate users were able to meet the study defined vaccine response in the majority of methotrexate users in at least 1 endpoint. Two studies examined vaccine disruption for influenza vaccines and demonstrated improved vaccine response to methotrexate users who discontinued therapy. Dosing of methotrexate was identified in 3 studies as having an impact on vaccine response.

Based off review of previous vaccine literature, a temporary hold of methotrexate in the post vaccination period may be a reasonable option to try boost the immune response to a novel vaccine.