In the majority of patients with rheumatoid arthritis (RA) who had an inadequate response to the antispike protein 1 (S1) with the previous 2 doses of the COVID-19 vaccine, a homologous third vaccine dose and temporary discontinuation of disease-modifying antirheumatic drug (DMARD) therapy are associated with a significant anti-S1 response, according to a comment published in the Lancet Rheumatology.

Authors of the report evaluated the efficacy and safety of a third dose of an mRNA-based anti-SARS-CoV-2 vaccine among patients with RA with an inadequate serologic response to the 2 previous doses of the vaccine.

In the current analysis, a third vaccination was offered to all patients with RA who had had participated in the RECOVER trial and not mounted an anti-S1 response within 12 weeks following the standard immunization schedule.

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A total of 17 patients with RA were eligible to receive a third dose of an mRNA COVID-19 vaccine between July 14 and August 25, 2021. Of these participants, 16 agreed to temporarily discontinue DMARD therapy. Only 1 patient continued to be treated with leflunomide and a tumor necrosis factor (TNF) inhibitor because of a prior relapse of comorbid Crohn disease.

Low or absent anti-S1 antibodies were confirmed prior to administration of the third vaccine dose (median, 19.5 U/mL; range, 0.45-48 U/mL). Two weeks after participants received their third vaccine dose, a significant increase in anti-S1 antibodies was reported (median, 2500 U/mL; range, 798-2500 U/mL; P <.0001). Overall, 71% (n=12/17) of the participants exhibited maximal anti-S1 titers (assay ceiling, 2500 U/mL); 3 patients had moderate anti-S1 titers.

In addition, 2 participants who continued receiving treatment with prednisone 5 mg per day did not have titers above the threshold of 133 U/mL after receiving the third vaccine dose, despite a pause in their DMARD medication. Overall, 35% (n=6/19) of the patients used concomitant prednisone at a median daily dose of 5 mg. Anti-S1 titers were significantly higher in participants receiving vs not receiving prednisone (median, 2500 U/L vs 515 U/mL, respectively; P =.001).

Following receipt of the third vaccine dose, local pain was reported in 35% (n=6/17) of the participants and systemic vaccine-associated side effects were reported in 53% (n=9/17) of the patients.

Limitations of this report were the small cohort size, short follow-up period, and the use of numerical anti-S1 response cutoffs.

Authors concluded, Studies with larger patient cohorts will allow analysis of the effect of different DMARD regimens on the kinetics of anti-S1 [titers] and whether and how long treatment discontinuation is necessary to optimize vaccine-induced anti-S1 responses.”

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


Schmiedeberg K, Vuilleumier N, Pagano S, et al. Efficacy and tolerability of a third dose of an mRNA anti-SARS-CoV-2 vaccine in patients with rheumatoid arthritis with absent or minimal serological response to two previous doses. Lancet Rheumatol. Published online October 26, 2021. doi:10.1016/S2665-9913(21)00328-3