Studies show people taking rheumatoid arthritis drugs have a weaker response to the SARS-CoV-2 vaccine

In a recent study posted on medrex sib* Preprint Server. Researchers conducted a comparative study among cohorts of individuals on rheumatoid arthritis (RA) treatment. vis à vis Healthy controls to assess response to coronavirus disease 2019 (COVID-19) vaccine.

Background

RA is an autoimmune disease that causes joint swelling, pain and weakness. Drugs used to treat RA actively suppress people’s immune systems, altering their response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. In preliminary clinical trials, BNT162b2 and messenger ribonucleic acid (mRNA)-1273 vaccines are ~95% Effectiveness Against COVID-19. However, these trials excluded immunocompromised patients, such as those receiving RA therapy.

With the emergence of SARS-CoV-2 variants that evade antibody-mediated protective immunity (such as Omicron), it is important to understand the response to COVID-19 vaccination in this high-risk population. The American College of Rheumatology acknowledges that disease-modifying anti-rheumatic drugs (DMARDs) impair effective COVID-19 vaccine-induced responses.

Methotrexate (MTX), the first-line treatment for RA, is an immunosuppressive drug believed to inhibit folic acid metabolism in lymphocytes that cause RA. Abatacept binds to antigen-presenting cells and blocks costimulation to pathogenic autoreactive T cells that cause RA. It may also inhibit neutralizing antibody responses induced by mRNA vaccines in RA patients. Similarly, the RA drug rituximab is thought to deplete her B cells, resulting in a severely impaired immune response to her mRNA-based COVID-19 vaccine.

About research

In the current multicenter study, researchers collected blood samples from RA subjects who received the first vaccination series of BNT162b2 or mRNA-1273 vaccines. The study cohort consisted of her 40 subjects, 27 of whom were RA and 13 of whom were age- and sex-matched healthy controls. Of her 27 RA subjects, 11 received her MTX and her other 11 received abatacept treatment. The remaining five of her received rituximab therapy.

The team collected donor blood samples within 1-3 weeks and in some cases within 3 months after vaccination for serum and PBMC isolation and humoral and cellular analyses. First, we measured antibody responses to her SARS-CoV-2 spike(S) in the patient’s serum. In addition, they examined the abundance, phenotype, and functionality of SARS-CoV-2-specific T and B cells.

In addition, researchers pseudovirus Neutralization (pVNT) assay. This will help assess whether sera from SARS-CoV-2 naïve and unvaccinated individuals undergoing RA therapy effectively block angiotensin-converting enzyme 2 (ACE-2) infection. I was.

Investigation result

Both Abatacept and MTX reduce antibody production in response to SARS-CoV-2 mRNA vaccines. MTX-treated RA subjects had significantly greater magnitude of SARS-CoV-2 S-specific differentiation cluster (CD4) + T cell responses to COVID-19 mRNA vaccine by T-cell activator-inducible marker (AIM) assay confirmed to be low. However, the numbers of phenotypically and functionally specific CD4+ T cells and RBD-specific B cells were comparable to healthy subjects. Conversely, most RA subjects who received the B-cell depleting antibody rituximab had no detectable her S-specific antibody response in serum.

Similarly, in RA subjects treated with abatacept, CD4+ memory T cells, IgG+ memory B cells, and Neutralizing antibody COVID-19 vaccination compromised. Additionally, the researchers noted a significant reduction in the magnitude of cytokines such as interleukin (IL) 2 & 21 and interferon-gamma (IFNγ). Furthermore, they found that abatacept treatment decreased her T follicular helper (Tfh) cell numbers, Tfh cell-associated IL-12 levels, and impaired transcription of T cell proliferation. Strikingly, withdrawal of drug treatment almost instantaneously reversed the effects of abatacept on Tfh cell size and transcriptional profile.

Another important observation was decreased serum neutralizing activity in RA patients receiving abatacept therapy. Although quantitatively impaired, the quality of antibodies produced in subjects treated with MTX and abatacept was normal.

Conclusion

Neutralizing antibody titers induced by vaccination are well-established correlates of protection against viral pathogens, including SARS-CoV-2. Therefore, the significant reduction in anti-SARS-CoV-2 S antibodies observed in the abatacept cohort was clinically relevant. The authors suggested that abatacept treatment in patients with RA is beneficial and should be discontinued during the vaccination period. It may significantly improve responses to SARS-CoV-2 vaccines and protect immunocompromised populations from future SARS-CoV-2 variants.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .