Methotrexate significantly reduces the humoral vaccination response against SARS-CoV-2 in older but not younger patients with rheumatoid arthritis

Rheumatol Int. 2022 Jun;42(6):959-966. doi: 10.1007/s00296-022-05123-2. Epub 2022 Apr 16.

Abstract

To assess the humoral response to vaccination against SARS-CoV-2 in patients with rheumatoid arthritis treated with methotrexate (MTX). In total, 142 fully vaccinated individuals were included at 6 ± 1 weeks after their second vaccination [BioNTech/Pfizer (70.4%), AstraZeneca (20.4%), and Moderna (9.2%)]. The primary goal was to assess the humoral immune response as measured by titres of neutralising antibodies against the S1 antigen of SARS-CoV-2. In a cross-sectional, single-centre study, titres were compared between patient subgroups with (n = 80) and without (n = 62) methotrexate exposure. MTX patients showed a significantly reduced humoral response to vaccination in the oldest patient subgroup (> 70 years: P = 0.038), whereas titres of neutralising antibodies were not significantly different between MTX and non-MTX patients in patients less than 70 years of age (< 56 years: P = 0.234; 56-70 years: P = 0.446). In patients > 70 years, non-MTX patients showed a maximum immune response in 76.5% of cases, whereas this percentage was reduced to 53.7% in study participants on MTX medication (effect size d = 0.21). Older age in patients with rheumatoid arthritis in combination with methotrexate results in a significantly reduced humoral response after vaccination against SARS-CoV-2. Our data underline the importance of age regarding the humoral response and may support the temporary cessation of methotrexate, particularly in elderly patients in the context of vaccination against SARS-CoV-2.

Keywords: Arthritis; COVID-19; Immune response; Methotrexate; Rheumatoid; SARS-CoV-2; Vaccination.

MeSH terms

  • Aged
  • Antibodies, Neutralizing / therapeutic use
  • Antibodies, Viral
  • Arthritis, Rheumatoid* / drug therapy
  • COVID-19* / prevention & control
  • Cross-Sectional Studies
  • Humans
  • Methotrexate / therapeutic use
  • Middle Aged
  • SARS-CoV-2
  • Vaccination

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Methotrexate