Holding Methotrexate After Second COVID-19 Vaccine Dose May Be Best in Psoriatic, Rheumatoid Arthritis

In patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA), withholding methotrexate for 2 weeks after vaccination with ChAdOx1 nCov-19 (AstraZeneca) for COVID-19 led to a higher antibody response compared with the continuation of methotrexate, although this was accompanied by an increased risk of disease flare. This is according to research published in The Lancet Rheumatology,¹ which found withholding methotrexate only after the second vaccine dose may carry a lower risk for disease flare, with no considerable difference in the antibody response.

“This finding remained despite the wide gap between the 2 doses of the ChAdOX1 n COV-19 vaccine (12–16 weeks) and could be translated into practice by withholding methotrexate only during the second dose of vaccine to achieve an optimal trade-off between immunogenicity and risk of flare,” Padmanabha Shenoy, DM, of the Centre for Arthritis and Rheumatism in Cochin, India, and colleagues, noted.

An optimal COVID-19 vaccination strategy is essential for vulnerable population groups, including people with autoimmune inflammatory arthritis on immunosuppressants such as methotrexate, which inhibit vaccine-induced immunity against SARS-CoV-2. However, the evidence supporting methotrexate withdrawal at the time of COVID-19 vaccination is scarce, especially for the ChAdOx1 nCoV-19 vaccine.

Between July 6 and December 15, 2021, participants were recruited to 2 parallel, randomized trials, dubbed MIVAC I and MIVAC II. Researchers assessed the post-vaccination antibody titers and disease flare rates that resulted from withholding methotrexate for 2 weeks after each dose of the ChAdOx1 nCov-19 vaccine (MIVAC I) or only after the second dose of vaccine (MIVAC II) compared with continuation of methotrexate. The trials, which were undertaken at a single center in India, included people with either PsA or RA with stable disease activity, who had been on a fixed dose of methotrexate for the preceding 6 weeks. People with previous COVID-19 or who were positive for anti-SARS-CoV-2 nucleocapsid antibodies were excluded, as were those on high-dose corticosteroids and rituximab. The primary outcome for both trials was the titer of anti-receptor binding domain (RBD) antibody measured 4 weeks after the second vaccine dose.

In MIVAC I, a total of 158 participants (94% women) completed the study. The median post-vaccination antibody titers in the methotrexate hold group (n=80, 14% PsA) were significantly higher compared with the control group (n=78, 8% PsA) (2484.0 IU/mL, IQR 1050.0–4388.8 vs 1147.5 IU/mL, 433.5–2360.3; p=0.0014). Meanwhile, 25% of the methotrexate hold group and 8% of the methotrexate continuation group had a disease flare after the first vaccine dose (p=0.0050). After the second vaccine dose, the respective rates were 24% and 13% (p=0.10).

In MIVAC II, a total of 157 participants (86% women) completed the study. The methotrexate hold group (n=76, 8% PsA) had higher post-vaccination antibody titers compared with the control group (n=81, 1% PsA) (2553.5 IU/ml, IQR 1792.5–4823.8 vs 990.5, 356.1–2252.5; p<0.0001). However, no significant difference was found in the proportion of participants with a disease flare between the groups (12% of the methotrexate hold group vs 5% of the methotrexate continuation group; p=0.15).

No serious adverse events were reported during the trial period.

“Interruption of methotrexate during the second dose of ChAdOx1 nCov-19 vaccine appears to be a safe and effective strategy to improve the antibody response in patients with rheumatoid or psoriatic arthritis,” investigators concluded.

Reference:

Skaria TG, Sreeprakash 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 two, parallel, assessor-masked, randomised controlled trials. Lancet Rheumatol. 2022;4(11):e755-e764. doi:10.1016/S2665-9913(22)00228-4