T-cell responses to BNT162b2 vaccine not weakened by methotrexate

Patients with psoriasis taking the immunosuppressant methotrexate had low antibody responses to SARS-CoV-2 after receiving the first dose of Pfizer-BioNTech’s BNT162b2 vaccine but had shown T-cell responses, according to a study that was the first to look at T-cell responses in patients taking methotrexate.

In those taking targeted biologics, both antibody and T-cell responses were preserved.

“These results suggest that seroconversion alone might not adequately reflect vaccine immunogenicity in those with immune-mediated inflammatory diseases receiving therapeutic immunosuppression,” said lead author Dr Satveer Mahil, a consultant dermatologist at the St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust in London, UK. “Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness.”

Mahil said patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. Hence, data on how well the vaccines work in this population, including in patients with psoriasis, have been limited.

This prompted his group to evaluate the immune responses to the BNT162b2 vaccine of patients with psoriasis taking methotrexate and commonly used biologics vs 17 healthy controls without psoriasis. [ECCMID 2021, abstract 2782-2; Lancet Rheumatol 2021;doi: 10.1016/S2665-9913(21)00217-5] 

Patients (median age 43 years, 55 percent male, 84 percent White) were enrolled from January to April 2021. None of them had a COVID-19 infection. Of 84 patients with psoriasis, 17  were on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors.

Immune response was measured prior to receiving the first dose of the vaccine and 28 days later. The primary outcomes were humoral immunity (neutralising antibody response) to the SARS-CoV-2 virus and T-cell responses 28 days post-vaccination.

Seroconversion rates         

Four weeks after receiving the vaccine, rates of seroconversion (development of antibodies vs the virus) were lower in patients receiving immunosuppressants vs the controls (78 percent vs 100 percent). Patients taking methotrexate had the lowest seroconversion rate (47 percent), which correlated with lower levels of neutralising antibodies (that which stop the entry of virus to the cells) in the methotrexate group (median 50 percent inhibitory dilution 129, interquartile range [IQR] 40–236) vs the controls (317, IQR 213–487;p=0.0032), but were preserved in patients taking the biologics (269).

T-cell responses were detected in all groups at comparable rates and levels, even in those without evidence of seroconversion. Neutralising titres against the Alpha (B117) variant were similarly low in all groups.

Findings after the second dose are eagerly awaited.

Data reassuring

Despite the massive roll-out of COVID-19 vaccines globally, concerns over vaccine efficacy in immunocompromised patients remain.

“That the T-cell responses were not affected after the first dose of BNT162b2 vaccine in those taking methotrexate or a biologic therapy – including in some of those who didn’t seroconvert – is reassuring,” said co-investigator Professor Catherine Smith, St John’s Institute of Dermatology, Kings College London and Guys and St Thomas’ Hospital, London, UK. “Still, continuous monitoring of these patients is needed to determine what this means for the clinical effectiveness of the vaccines.”

Findings not consistent

Drs Caoilfhionn  Connolly and Julie Paik from the Johns Hopkins University School of Medicine, Baltimore, Maryland, US, meanwhile, commented:  “Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups. During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.” [Lancet Rheumatol 2021;doi:10.1016/S2665-9913(21)00217-4]

Additionally, the findings highlight the importance of administering both doses of the BNT162b2 vaccine within the approved schedule to reduce the burden of COVID-19 in this vulnerable population, added the experts.