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  • Review Article
  • Published:

Effect of DMARDs on the immunogenicity of vaccines

Nature Reviews Rheumatology volume 19, pages 560–575 (2023)Cite this article

Subjects

Abstract

Vaccines are important for protecting individuals at increased risk of severe infections, including patients undergoing DMARD therapy. However, DMARD therapy can also compromise the immune system, leading to impaired responses to vaccination. This Review focuses on the impact of DMARDs on influenza and SARS-CoV-2 vaccinations, as such vaccines have been investigated most thoroughly. Various data suggest that B cell depletion therapy, mycophenolate mofetil, cyclophosphamide, azathioprine and abatacept substantially reduce the immunogenicity of these vaccines. However, the effects of glucocorticoids, methotrexate, TNF inhibitors and JAK inhibitors on vaccine responses remain unclear and could depend on the dosage and type of vaccination. Vaccination is aimed at initiating robust humoral and cellular vaccine responses, which requires efficient interactions between antigen-presenting cells, T cells and B cells. DMARDs impair these cells in different ways and to different degrees, such as the prevention of antigen-presenting cell maturation, alteration of T cell differentiation and selective inhibition of B cell subsets, thus inhibiting processes that are necessary for an effective vaccine response. Innovative modified vaccination strategies are needed to improve vaccination responses in patients undergoing DMARD therapy and to protect these patients from the severe outcomes of infectious diseases.

Key points

  • Vaccines should ideally evoke efficient interactions between antigen-presenting cells and T cells and B cells; certain DMARDs disturb these interactions, leading to reduced vaccine responses and protection from infection.

  • The immunogenicity of influenza and SARS-CoV-2 vaccines is often reduced in patients with rheumatic diseases, depending on the type of DMARD used during vaccination.

  • A few DMARDs substantially inhibit responses to both vaccines (such as B cell depletion therapy or mycophenolate mofetil), whereas other DMARDs likely have no effect (including IL-6 inhibitors and hydroxychloroquine).

  • The effect of some DMARDs (including TNF inhibitors, methotrexate and glucocorticoids) on vaccine responses could depend on the type of vaccine or DMARD dose used.

  • The differential effects of DMARDs on vaccine responses are likely explained by the varying ways in which these drugs target disease and the functioning of antigen-presenting cells, T cells and B cells.

  • Specific vaccine strategies, such as a drug holiday, should be considered for patients on each type of DMARD, depending on their effects on vaccine effectiveness and on controlling disease activity.

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Fig. 1: Immune responses after vaccination.
Fig. 2: The effect of DMARDs on immunological processes important for vaccine responses.

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, the Netherlands

    Yannick van Sleen, Kornelis S. M. van der Geest & Elisabeth Brouwer

  2. Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, Groningen, the Netherlands

    Anke L. W. Huckriede & Debbie van Baarle

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  1. Yannick van Sleen
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  2. Kornelis S. M. van der Geest
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  3. Anke L. W. Huckriede
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  5. Elisabeth Brouwer
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Y.v.S. researched data for the article and wrote the article. All authors contributed substantially to discussions of content and reviewed and/or edited the manuscript before submission.

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Correspondence to Yannick van Sleen or Elisabeth Brouwer.

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Nature Reviews Rheumatology thanks M. Kapetanovic, A. Medeiros-Ribeiro and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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van Sleen, Y., van der Geest, K.S.M., Huckriede, A.L.W. et al. Effect of DMARDs on the immunogenicity of vaccines. Nat Rev Rheumatol 19, 560–575 (2023). https://doi.org/10.1038/s41584-023-00992-8

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