Third dose of mRNA COVID-19 vaccine in patients with RA with an inadequate response to previous doses – Community News

Third dose of mRNA COVID-19 vaccine in patients with RA with an inadequate response to previous doses

In the majority of rheumatoid arthritis (RA) patients who had an inadequate response to antispike protein 1 (S1) with the previous 2 doses of the COVID-19 vaccine, a homologous third vaccine dose, and temporary discontinuation of the 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 in patients with RA who had an inadequate serological response to the 2 previous doses of the vaccine.

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

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A total of 17 patients with RA were eligible for 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 was further treated with leflunomide and a tumor necrosis factor (TNF) inhibitor because of a previous recurrence of comorbid Crohn’s 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 participants exhibited maximal anti-S1 titres (test ceiling 2500 U/ml); 3 patients had moderate anti-S1 titres.

In addition, 2 participants who continued to receive prednisone 5 mg per day had no titers above the 133 U/ml threshold after receiving the third vaccine dose, despite a pause in their DMARD medication. Overall, 35% (n=6/19) of patients were on concomitant prednisone at a median daily dose of 5 mg. Anti-S1 titres were significantly higher in participants receiving or not receiving prednisone (median, 2500 U/L vs 515 U/ml, respectively; p =.001).

After receiving the third vaccine dose, local pain was reported in 35% (n=6/17) of participants and systemic vaccine-related adverse events were reported in 53% (n=9/17) of patients.

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

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

Disclosure: Some authors have stated affiliations with biotech, pharmaceutical, and/or device companies. 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 anti-SARS-CoV-2 mRNA vaccine in rheumatoid arthritis patients with absent or minimal serological response to two prior doses. lancet rheumatoid. Published online October 26, 2021. doi:10.1016/S2665-9913(21)00328-3

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