Certain DMARDs Reduce Vaccine Efficacy in Patients With RA


“These data suggest that vaccine responses are reduced but can be improved by sufficient vaccine/virus exposure,” investigators stated.

Patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs) appeared to have a reduced response rates to the SARS-CoV-2 vaccination, according to a study published in RMD Open.1 While responses improved with second and third doses, approximately 10% of patients remained seronegative.

“These data suggest that vaccine responses are reduced but can be improved by sufficient vaccine/virus exposure,” investigators stated. “The data support the use of a third dose of the vaccination with cessation of specific drugs to optimize response.”

A total of 107 patients with RA on various DMARDs, along with 9 healthy controls, were assessed for antibody and T cell analysis both pre-vaccination and 4 weeks post-vaccination. A positive antibody response was defined as sera IgG binding to ≥1 antigen. Those who continued to be seronegative after the first dose of the vaccine were tested 4 weeks after the second dose. If they remained seronegative, they were retested after a third dose. T cell response was determined by a T-Spot-Covid ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens.

Roughly half (45%) of patients (n = 37/83) had a vaccine-specific antibody response after the first dose of the vaccine, 53% (n = 44/83) had vaccine specific T cell responses, and 77% (n = 64/83) had either antibody or T cell responses.

Patients receiving abatacept (0%; n = 0/11), rituximab (RTX) (35%; n = 10/29), and concomitant methotrexate (MTX) (p=0.01, OR: 8, 95% CI: 1.63 to 37.98) were more likely to experience reduced seroconversion when compared with controls.

Those receiving anti-tumor necrosis factor (TNF) drugs had better seroconversion when compared with those receiving RTX (p=0.012, OR: 12, 95% CI: 1.71 to 85.24). Seroconversion was seen in 65% (n = 17/26) of patients taking anti-TNF, 56% (n =5/9) taking Janus Kinase inhibitors (JAKi), and 63% (n = 5/8) of those taking anti-interleukin 6 (IL-6). However, antibody responses were found in 100% of the health controls.

Patients who were exposed to COVID-19 prior to their vaccination were 17 times more likely to develop seroconversion (≥3 antibodies) (p<0.001).

For those in the non-seroconverters group, a second dose of the vaccine produced seroconversion in 54% (n = 19/35) and a third dose produced it in 20% of the 10 remaining patients.

An age of ≤50 years (p=0.012, OR: 18, 95% CI: 1.87 to 179.09) was also associated with seroconversion after the first vaccine dose.

The requirement for baseline samples limited the study as investigators were only able to recruit a small number of patients, particularly in the control group. However, the 100% seroconversion rate validates the analysis.

“These data confirm reduced immune responses to SARS-CoV-2 vaccine in patients with RA particularly on certain DMARDs,” investigators concluded. “The impact of a booster dose in patients with absent antibody responses to a 3 dose vaccination schedule will need to be determined.”


Saleem B, Ross RL, Bissell LA, et al. Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses. RMD Open. 2022;8(1):e002050. doi:10.1136/rmdopen-2021-002050

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