Abstract
SummaryBackgroundCOVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. Here, we aimed to assess immune responses following the second dose.MethodsIn this longitudinal cohort study, we recruited individuals with psoriasis who were receiving methotrexate or targeted biological monotherapy (ie, tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South-East England. The healthy control cohort were volunteers without psoriasis, not receiving immunosuppression. Immunogenicity was evaluated 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, and cellular immunity defined as spike-specific T-cell responses (including numbers of cells producing interferon-γ, IL-2, IL-21).FindingsBetween 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), and 15 healthy controls, who had received both vaccine doses. The median age of the study population was 44 years (IQR 33–52), 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 similar 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 32–86) and targeted biologics (37 [74%] of 50, 60–85; p=0·38) had detectable T-cell responses following the second vaccine dose, compared with controls (14 [100%] of 14, 77–100; p=0·022). There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 106 cells 160 [IQR 10–625]), targeted biologics (169 [25–503], p=0·56), and controls (185 [133–328], p=0·41).InterpretationFunctional 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.FundingNIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London; The Psoriasis Association.
Highlights
Individuals with immune-mediated inflammatory dis eases were shown to be at increased risk of COVID-19related 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
Added value of the study We evaluated the effect of methotrexate and biologics targeting tumour necrosis factor, interleukin (IL)-17, and IL-23 on humoral and cellular immune responses to the second dose of the COVID-19 vaccine BNT162b2 in individuals with psoriasis
Implications of all the available evidence These findings indicate that functional humoral immunity at 14 days after a second dose of the BNT162b2 COVID-19 vaccine was not impaired by methotrexate or targeted biologics
Summary
Individuals with immune-mediated inflammatory dis eases were shown to be at increased risk of COVID-19related 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 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 similar. The OCTAVE study, involving a heterogeneous cohort of patients with immunemediated inflammatory diseases, indicated lower serological and similar T-cell responses to two vaccine doses, compared with healthy controls. No studies have concurrently assessed immunosuppressantspecific effects on serological, neutralising antibody (including against the delta variant) and cellular responses to a second vaccine dose, administered at an extended interval, in patients with immune-mediated inflammatory diseases. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. We aimed to assess immune responses following the second dose
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