Commentary: Humoral and cellular immunogenicity to a second dose of COVID-19 vaccine BNT162b2 in people receiving methotrexate or targeted immunosuppression: a longitudinal cohort study

In a study published in The Lancet Rheumatology, a research group led by Catherine Smith from St John’s Institute of Dermatology described humoral and cellular immunity against SARS-CoV-2 spike glycoprotein in sixty-seven patients with psoriasis as compared to fifteen healthy controls after the second dose of the COVID-19 vaccine BNT162b2 (Pfizer-BioNTech). Patients included in the study received methotrexate (n=14), TNF inhibitors (n=19), IL-17 inhibitors (n=14), or IL-23 inhibitors (n=20). The median age was 44 years, with 52% males and 87% of White ethnicity. The study demonstrated that functional humoral immunity was not impaired by methotrexate or biologics, as observed that after the second dose of vaccine, as both patients and controls had neutralizing antibodies against wild-type SARS-CoV-2 and two variants. However, 38% of 13 participants on methotrexate and 26% of 50 participants on targeted biologics did not have detectable T-cell responses following the second dose of vaccine. There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 10⁶ cells 160, targeted biologics (169), and controls (185).

The observations on antibody development after COVID-19 vaccination in patients treated with methotrexate or targeted immunosuppressive agents are reassuring. However, the observation of absence of boosting of T-cell responses might indicate that durable cellular and humoral immunity may be impaired in some of the patients receiving these drugs.

Implications

• Pending further investigations, the study by Mahil et al supports the prioritization of a further vaccine dose in patients with psoriasis receiving therapeutic immunosuppression, since 18 (29%) of their immunosuppressed cohort (63 patients) had undetectable cellular responses following a second dose.

• It is essential to conduct studies with clinical outcomes in patients receiving immune-suppressive medications to assist clinical decision making about short-term treatment discontinuation at the time of vaccination or the need of additional booster vaccinations in these patients.

• As the durability of antibody responses in the context of undetectable cellular responses is unknown, it is important that future research will focus on this aspect.

Limitations

Limitations of the study are that patients with psoriasis not receiving immunosuppressants were not included, and that most participants were of White ethnicity. As the number of patients included and study and the duration of follow-up are limited, it is possible that differences may become statistically significant with a larger sample size or with longer follow-up.