Holding Methotrexate in RA/PsA After Second Dose of COVID-19 Vaccine Improves Antibody Response

Holding vs continuing MTX after the second dose of the COVID-19 vaccine resulted in higher anti-RBD antibody titers.

In patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA), holding vs continuing methotrexate (MTX) after the second dose of the ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine results in a higher antibody response, according to the results of a study published in The Lancet Rheumatology.

Researchers sought to evaluate the impact of holding MTX for 2 weeks after each dose of the COVID-19 vaccine (MIVAC I) or only after the second dose of the vaccine (MIVAC II), compared with the continuation of MTX, on postvaccination antibody titers and rate of disease flares.

Two parallel, independent, assessor-masked, randomized trials were conducted at a single center in Kochi, India (Dr Shenoy’s Centre for Arthritis and Rheumatism Excellence) among patients with RA and PsA with stable disease activity who had been receiving a fixed dose of MTX for 6 weeks prior.

In MIVAC I, participants were randomly assigned 1:1 to halt MTX treatment for 2 weeks following each of the 2 vaccine doses or to continue MTX therapy. In MIVAC II, participants in whom MTX was continued during the first vaccine dose were randomly assigned in 1:1 to hold MTX for 2 weeks following the second vaccine dose or to continue the treatment.

Future studies should measure how this change in practice affects the risk of breakthrough infections during booster doses in a real-life scenario.

For both MIVAC I and MIVAC II, the primary study outcome was the titer (absolute value) of antireceptor binding domain (RBD) antibody, which was measured 4 weeks after the second dose of the COVID-19 vaccine. Participants were enrolled into both the trials between July and December 2021.

In MIVAC I, a total of 250 participants were enrolled, with 158 individuals completing the study (80 in the MTX-hold group and 78 in the control group; 148 women). In the MTX-hold group, the median postvaccination antibody titers were significantly higher than in the control group (2484.0 IU/mL [IQR, 1050.0-4388.8 IU/mL] vs 1147.5 IU/mL [IQR, 433.5-2360.3 IU/mL], respectively; P =.0014).

In MIVAC II, a total of 178 participants were enrolled, with 157 individuals completing the study (76 in the MTX-hold group and 81 in the control group; 135 women). In the MTX-hold group, the median postvaccination antibody titers were significantly higher than in the control group (2553.5 IU/mL [IQR, 1792.5-4823.8 IU/mL] vs 990.5 IU/mL [IQR, 356.1-2252.5 IU/mL], respectively; P <.0001).

Although holding MTX following both vaccine doses as well as after only the second dose was associated with higher anti-RBD antibody titers compared with the continuation of MTX, holding MTX after the second vaccine dose only was linked to a similar humoral response to holding MTX following both vaccine doses, with no increased risk for arthritis flares.

Because India was in its second and third waves of COVID-19 during the trial period, potential participants were excluded from the study due to SARS-CoV-2 infection. Further, the study populations might not be representative of all patients with immune-mediated inflammatory diseases who were receiving MTX as some of them were receiving corticosteroid doses of less than 5 mg and rituximab and were, hence, excluded from the study.

Because holding MTX after the second vaccine dose only was associated with similar immunogenicity and a lower risk for disease flares compared with holding MTX after both vaccines doses, the study authors concluded that, “Future studies should measure how this change in practice affects the risk of breakthrough infections during booster doses in a real-life scenario.”

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

This article originally appeared on Rheumatology Advisor

References:

Skaria TG, Sreepakasah A, Umesh R, et al. Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of 2, parallel, assessor-masked, randomised controlled trials. Lancet Rheumatol. Published online September 12, 2022. doi:10.1016/S2665-9913(22)00228-4