Statistical imbalance of the baseline characteristics across the treatment groups presented by either Kruskal-Wallis or 2. immediately before, on day 28 after the first BNT162b2 vaccination and on day 14 after the second dose (administered according to an extended interval regimen). Here, we report immune responses following the second dose. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as titres of total spike-specific IgG and of neutralising antibody to wild-type, alpha (B.1.1.7), and delta (B.1.617.2) SARS-CoV-2 variants, Piboserod and cellular immunity defined as spike-specific T-cell responses (including numbers Piboserod of cells producing interferon-, IL-2, IL-21). Findings Between Jan 14 and April 4, 2021, 121 individuals were recruited, and data were available for 82 participants after the second vaccination. The study population included patients with psoriasis receiving methotrexate (n=14), TNF inhibitors (n=19), IL-17 inhibitors (n=14), IL-23 inhibitors (n=20), Piboserod and 15 healthy controls, who had received both vaccine doses. The median age of the study population was 44 years (IQR 33C52), with 43 (52%) males and 71 (87%) participants of White ethnicity. All participants had detectable spike-specific antibodies following the second dose, and all groups (methotrexate, targeted biologics, and healthy controls) demonstrated comparable neutralising antibody titres against wild-type, alpha, and delta variants. By contrast, a lower proportion of participants on methotrexate (eight [62%] of 13, 95% CI 32C86) and targeted biologics (37 [74%] of 50, 60C85; p=038) had detectable T-cell responses following the second vaccine dose, compared with controls (14 [100%] of 14, 77C100; p=0022). There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 106 cells 160 [IQR 10C625]), targeted biologics (169 [25C503], p=056), and controls (185 [133C328], p=041). Interpretation Functional humoral immunity (ie, neutralising antibody responses) at 14 days following a second dose of BNT162b2 was not impaired by methotrexate or targeted biologics. A proportion of patients on immunosuppression did not have detectable T-cell responses following the second dose. The longevity of vaccine-elicited antibody responses is unknown in this population. Funding NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London; The Psoriasis Association. Introduction Individuals with immune-mediated inflammatory diseases were shown to be at increased risk of COVID-19-related death compared with the general population.1 Based on previous research in other infections and registry data collected during the COVI-19 pandemic,2, 3, 4 there has been concern over the detrimental effect of systemic immunosuppressants (the mainstay of treatment of moderate to severe immune-mediated inflammatory diseases) on Piboserod COVID-19 outcomes. Vaccination is usually therefore a vital risk mitigating strategy in this population. General population-based studies indicate that two doses of a COVID-19 vaccine provides protection against SARS-CoV-2 infections and related adverse outcomes.5, 6 However, immunogenicity and clinical effectiveness in patients with immune-mediated inflammatory diseases who are receiving immunosuppressants remains uncertain. These patients were excluded from COVID-19 vaccine trials and most previous studies have focused on seroconversion alone,7, 8, 9, 10 which might not Rabbit Polyclonal to POLE1 adequately reflect vaccine immunogenicity or correlate with effectiveness. Research in context Evidence before this study Two COVID-19 vaccine doses, administered according to an extended interval regimen, are highly efficacious at protecting against SARS-CoV-2 infections and adverse COVID-19 outcomes in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remain scarce. Understanding vaccine immunogenicity in this vulnerable population is usually of major importance to public and individual health. The interim analysis of our cohort study at day 28 (after one dose) showed that methotrexate but not targeted biologics impaired functional humoral immunity (ie, neutralising antibody responses) to the first dose of the COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas T-cell responses were comparable. Piboserod The OCTAVE study, involving a heterogeneous cohort of patients with immune-mediated inflammatory diseases, indicated lower serological and comparable T-cell responses to.