Two Doses of mRNA COVID-19 Vaccine Required to Induce Robust Immune Response in Patients With Inflammatory Joint Diseases

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Researchers assessed the immune response of patients with rheumatoid arthritis and seronegative spondyloarthritis to mRNA COVID-19 vaccination after the first and second dose.

Patients with inflammatory diseases, including rheumatoid arthritis (RA) and spondyloarthritis (SpA), receiving treatment with immunomodulatory medications resulted in an impaired immune response against COVID-19 after the first dose of the mRNA vaccine but a robust response after the second dose of the vaccine, according to study results published in Annals of the Rheumatic Diseases.

The authors of the current study sought to investigate the kinetics of humoral response after the first and second dose of COVID-19 mRNA vaccines in patients with inflammatory joint diseases receiving disease-modifying antirheumatic drug (DMARD) monotherapy.

Patients with an established diagnosis of RA and seronegative SpA were included in the study and those receiving B-cell depleting therapies were excluded. Researchers analyzed the characteristics of the humoral response and effect of therapies on vaccine efficacy in patients with inflammatory joint diseases compared with healthy individuals.

A total of 99 patients (RA, 53; SpA, 46) and 169 control participants were included in the study.

Results of the study showed that seroconversion rates, which determine vaccine efficacy, were significantly lower in the patient cohort (52.5% and 54.8% in patients with RA and SpA, respectively) after the first dose of mRNA vaccine, whereas the healthy control cohort had an efficacy of 98%. After the second dose of mRNA vaccine, the efficacy was 100% in both the patient and healthy control cohorts.

The median titer levels of antibodies against the spike protein of SARS-CoV-2 were significantly lower after the first dose in patients with RA (median, 0.61 BAU/mL) and SpA (median, 1.65 BAU/mL) compared with healthy individuals (median, 43.3 BAU/mL). However, no differences in median titer levels were observed between the patient and healthy control group after the second dose.

Overall, DMARDs were not found to affect antibody levels. However, antibody titers were reduced even after the second dose in patients receiving a combination of conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic DMARD (b/tsDMARDs) compared with patients receiving only csDMARDs and those who were healthy. The efficacy rates were similar between patients receiving csDMARDs and healthy individuals after the second dose.

The researchers concluded, “The current study suggests that most patients with inflammatory joint diseases need both vaccinations to develop a substantial antibody response. It is therefore important for the management of patients with inflammatory joint diseases that non pharmaceutical protective measures are mandatory until completion of the full vaccination schedule.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Simader E, Tobudic S, Mandl P, et al. Importance of the second SARS-CoV-2 vaccination dose for achieving serological response in patients with rheumatoid arthritis and seronegative spondyloarthritis. Ann Rheum Dis. Published online November 29, 2021.  doi:10.1136/annrheumdis-2021-221347