Third Dose of mRNA COVID-19 Vaccine in Patients With RA With an Inadequate Response to Previous Doses

vaccine hesitancy in minorities
TAMPA, FL – FEBRUARY 13: Bible-Based Fellowship Church partnered with the Pasco County Health Department, and Army National Guard to assist residents who are 65 and older to administer the Moderna Covid-19 vaccine on February 13, 2021 in Tampa, Florida. Pastor Anthony White of Bible-Based Fellowship Church encourages more people from the African American community to receive the vaccine.(Photo by Octavio Jones/Getty Images)
Authors of a report published in Lancet Rheumatology reported on the safety and tolerability of a third mRNA COVID-19 vaccine dose in patients with rheumatoid arthritis with an inadequate serologic response to the previous doses.

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.

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