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13-07-2021 | COVID-19 | News

Methotrexate dulls humoral but not cellular response to COVID-19 vaccine

Author: Laura Cowen


medwireNews: UK research suggests there is a disparity between humoral and cellular immune responses to the first dose of the Pfizer–BioNTech (BNT162b2) COVID-19 vaccine in people on methotrexate monotherapy for psoriasis.

Catherine Smith (King’s College London) and colleagues found that functional humoral immunity to the vaccine “is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved.”

They therefore say: “When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population.”

The researchers report in The Lancet Rheumatology that, overall, people receiving immunosuppressants had a lower rate of seroconversion (78% of 77) at 28 days after their first vaccine dose than did healthy controls (100% of 17).

This difference was mainly driven by a seroconversion rate of just 47% among the 15 patients receiving methotrexate monotherapy and was higher in those receiving tumor necrosis factor (TNF) inhibitors (79% of 24), interleukin (IL)-23 inhibitors (83% of 23) and IL-17 inhibitors (100% of 15).

In addition, patients receiving methotrexate had significantly lower neutralizing activity against wild-type SARS-CoV-2 than controls (median 50% inhibitory dilution [ID50] 129 vs 317 units), whereas those receiving targeted biologics did not (269 units).

Conversely, Smith et al note that there was no difference between patients receiving immunosuppressants and controls in neutralizing titers against the B.1.1.7 (alpha) SARS-CoV-2 variant, which were low in both groups (median ID50 54 vs 61 units).

The investigators also looked at spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21 production) and found that response rates were similar across the groups, at 93%, 79%, 78%, 93%, and 69% for the methotrexate, TNF-inhibitor, IL-23 inhibitor, IL-17 inhibitor, and healthy control groups, respectively.

The authors comment: “While global mass COVID-19 vaccination programmes are underway, there remains concern over vaccine efficacy in immunosuppressed patients, including against novel SARS-CoV-2 variants that threaten immune escape.”

And they conclude: “Although our data indicating preserved cellular immunogenicity across biological classes and methotrexate, independent of neutralising activity, are reassuring, ongoing pharmacovigilance studies will determine whether this finding translates into clinical effectiveness of vaccines.”

They also note that the data on immune responses after the second vaccine dose will be reported at a later date.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

13 July 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00212-5