This is a summary, written by members of the CITF Secretariat, of:

Benoit JM, Breznik JA, Ang JC, Bhakta H, Huynh A, Cowbrough B, Baker B, Heessels L, Lodhi S, Yan E, Ewusie J, Nazy I, Bramson J, Miller MS, Bernatsky S, Larché MJ, Bowdish DME; SUCCEED Investigator Group. Immunomodulatory drugs have divergent effects on humoral and cellular immune responses to SARS-CoV-2 vaccination in people living with rheumatoid arthritis. Sci Rep. 2023 Dec 21;13(1):22846. doi: 10.1038/s41598-023-50263-5.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

A CITF-supported study, published in Scientific Reports, found that participants with rheumatoid arthritis (RA) on immunomodulatory drugs mounted diminished immune responses to SARS-CoV-2 vaccination. Different drug classes had impacts on the cellular and humoral compartments. The study looked at key elements of COVID-19 vaccine-induced protection — antibodies, CD4+ T cells, and CD8+ T cells – to determine if these are affected equally or in different ways by immunomodulatory drugs. The study was led by Dr. Dawn Bowdish (McMaster University) in collaboration with Dr. Sasha Bernatsky (McGill University) on behalf of the SUCCEED (Safety immUnogenicity of COVID-19 vacCines in systEmic immunE mediated inflammatory Diseases) Investigator Group.

This study determined how humoral and cellular SARS-CoV-2 vaccination responses differed between people with RA and controls. It also looked at which of the following drug classes had an impact on these responses: steroids, disease-modifying anti-rheumatic drugs (DMARDs), TNF and TNF receptor inhibitors, JAK inhibitors, and co-stimulation inhibitors (Abatacept).

From May 2021 to February 2023, blood was collected from adult participants (18+ years in age) with RA who were on immunomodulatory drugs (n=62, median age 63 years and 84% female), as well as from controls (n=35, median age 64 years and 66% female), after their second, third, and fourth SARS-CoV-2 vaccinations. Most participants with RA were on DMARDs (79%), 40% were on TNF inhibitors, 17% were on JAK inhibitors, 19% were on co-stimulation inhibitors, and 19% were on oral steroids. Receptor binding domain (RBD)-specific antibodies were quantified by ELISA. Spike-specific memory T cells were quantitated using flow cytometry. The impact of age, sex, and immunomodulatory drug classes on SARS-CoV-2 vaccination responses was assessed by statistical models.

Key findings:

  • Following SARS-CoV-2 vaccination, participants with RA on immunomodulatory drugs (n = 62) had lower anti-RBD IgG and spike-specific CD4+ T cell levels, compared to non-RA controls (n=35). No drug class was associated with deficits in spike-specific CD8+ T cells.
  • Additional vaccine doses and previous SARS-CoV-2 infection boosted the antibody levels in RA participants.
  • Individuals with RA on co-stimulation inhibitors had lower anti-RBD IgG responses to vaccination than those taking other classes of drugs.
  • JAK inhibitors were associated with lower spike-specific CD4+ T cells.

Overall, the study determined that participants with RA on immunomodulatory drugs generally mount weaker humoral and CD4+ T cell responses to SARS-CoV-2 vaccination than controls. However, the drug classes that affect these arms of immunity differ. Co-stimulation inhibitors were associated with weaker humoral responses, while JAK inhibitors were associated with lower levels of spike-specific CD4+ T cells. When evaluating a person’s risk of COVID-19, it will be critical to consider which drug classes patients are taking, as the drugs could differentially affect infection risk and long-term cross-variant protection.