The impact of methotrexate and targeted immunosuppression on cellular and humoral immune responses to COVID-19 vaccine BNT162b2: a cohort study

ABSTRACT

Individuals on immunosuppression were excluded from COVID-19 vaccine trials. We evaluated immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in people taking methotrexate and biologics. Given the roll out of extended interval vaccination programmes to maximise population coverage, we present findings following the first dose. We recruited individuals with psoriasis (n=84) established on methotrexate or biologic monotherapy (TNF, IL-17 or IL-23 inhibitors) and healthy controls (n=17). Immunogenicity was evaluated pre and post (day 28) vaccine. Seroconversion rates were lower in patients taking immunosuppression (78%, 95%CI 67-87%) compared to controls (100%, 95%CI 79-100%), with the lowest rate in those on methotrexate (50%, 95%CI 26-74%). Neutralising activity to wild-type SARS-CoV-2 was lower in patients receiving methotrexate (median ID50 152, IQR 47-257) compared to controls (median ID50 316, IQR 212-481, p<0.01), but preserved in those receiving biologics (median ID50 280, IQR 137-428). Neutralising titres against B.1.1.7 were comparably low in all participants. Spike-specific T cell responses (including IFNγ, IL-2, IL-21) were induced in all groups, and were equivalent among individuals receiving methotrexate, biologics and controls. Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by biologics, while cellular responses are unaffected. Seroconversion alone may not adequately reflect vaccine immunogenicity in individuals with immune-mediated disease receiving immunosuppression. Real-world pharmacovigilance studies will determine whether these findings translate to clinical effectiveness.