Methotrexate Treatment may jeopardize immune responses of COVID-19 vaccination in Rheumatoid Arthritis Patients: Study

MTX is widely accepted as the "gold standard" treatment for RA and commonly used to treat other IMIDs, including psoriatic arthritis (PsA) and spondyloarthritis (SpA). MTX inhibits purine and pyrimidine synthesis, which is required for cell division and, therefore, represents one of the most important anticancer drugs. Its anti-inflammatory effect in the treatment of IMID is poorly understood but may include blockade of NF-κB signaling, increased adenosine release, and T cell apoptosis.

Led by Laura YL Kummer, the study included 59 participants: 18 RA patients and 2 PsA patients receiving MTX monotherapy; 10 RA patients without immunosuppressive therapy; and 29 healthy controls. The researchers analyzed CD4 T cell and B cell responses 7 days and 3–6 months after two doses of the SARS-CoV-2 messenger RNA vaccines. To this end, they studied whole blood samples, antigen-specific CD4 T cells, and B cell activity through high-dimensional flow cytometry.

• 7 days after vaccination with two injections of the SARS-CoV-2 vaccines, MTX-treated patients had equivalent overall B and T cells count compared to controls.

• The frequencies of spike-specific B cells were unchanged by MTX treatment. More remarkably, MTX treatment reduced antigen-specific CD4 T cells to a very minimal level, which was well correlated with the levels of anti-RBD IgG antibodies.

• Patients in the MTX-treated group had inductions that were significantly lower than those of patients not treated with MTX, with a median of 0.17 (95% CI, 0.12 to 0.21) in comparison to 0.29 (95% CI, 0.18 to 0.39) for those not on MTX (P = 0.017).

• Antibody response was associated with very low antibody responses, as the level of induction of CD4 T cells could be inversely correlated with antibody responses, indicating that perhaps the treatment with MTX may delay the vaccination-induced immune response in RA patients.

• While the CD4 T cell activity was lower in the patients treated with MTX, the frequencies of spike-specific B cells were similar between these patients and controls.

The study concludes that MTX decreases specific CD4 T cell responses in patients with RA, an effect seemingly leading to kinetics of antibodies significantly decelerated. The clinical relevance of it all, as a whole, has yet to be shown however, the immune responses in such patients on MTX therapy would be vital toward being monitored as vaccination efforts proceed.

Reference:

Kummer LYL, Fernández Blanco L, Kreher C On behalf of the T2B! Immunity Against SARS-CoV-2 Study Group, et al. Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID. RMD Open 2024;10:e004664. doi: 10.1136/rmdopen-2024-004664