key: cord-0711797-ilmoi9yl
authors: Al‐Janabi, A.; Littlewood, Z.; Griffiths, C.E.M.; Hunter, H.J.A.; Chinoy, H.; Moriarty, C.; Yiu, Z.Z.N.; Warren, R.B.
title: Antibody responses to single‐dose SARS‐CoV‐2 vaccination in patients receiving immunomodulators for immune‐mediated inflammatory disease
date: 2021-06-04
journal: Br J Dermatol
DOI: 10.1111/bjd.20479
sha: 850bfaa0dfda1b343eee93f8b075e5721402a0ee
doc_id: 711797
cord_uid: ilmoi9yl

There are few data on whether immunomodulator therapy attenuates humoral response to vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some vaccines require two doses for maximum protection, with international variation in dosing schedules. A 3 month interval between doses is being used in the U.K. We evaluated antibody titres to SARS-CoV-2 following initial-dose BNT162b2 (Pfizer/BioNTech) or AZD1222 (AstraZeneca) vaccines in adults with psoriasis and other immune-mediated inflammatory diseases (IMIDs) receiving biologic and/or oral non-biologic immunomodulators.

antibody response to the single-dose BNT162b2 or AZD1222 vaccines; 41% had no detectable anti-S1 IgG. Anti-SARS-CoV-2 S appears more sensitive than the sCOVG assay. Nonbiologic immunomodulators, for example methotrexate, reduced the odds of a detectable antibody response compared with biologics: adjusted odds ratio (OR) 0Á31 [95% confidence interval (CI) 0Á08-1Á17] and OR 0Á18 (95% CI 0Á06-0Á59) for the Elecsys Anti-SARS-CoV-2 S and sCOVG assays, respectively ( Table 1 ). This contrasts with data from healthy populations, which show close to 100% seroconversion 14-35 days after the first vaccine dose, as measured by Roche Elecsys Anti-SARS-CoV-2 S or other spike-antigen-specific assays detecting IgG and total immunoglobulin. [1] [2] [3] [4] [5] No similar data for the sCOVG assay are available.

All of our participants with prior COVID-19 had antibodies detected by both assays after a single vaccination, in line with previous observations. 1,2 Increasing age was also associated nonlinearly with reduced odds of a positive antibody response: OR 0Á12 (95% CI 0Á03-0Á46) and OR 0Á12 (95% CI 0Á04-0Á39) for the Elecsys Anti-SARS-CoV-2 S and sCOVG assays, respectively, in those aged 60 years and over compared with those aged below 60 years, in a separate post hoc analysis. This is consistent with phase I trial data for the BNT162b2 vaccine, 4 and may be due to immunosenescence.

There have been few other studies examining the humoral response to SARS-CoV-2 vaccines in patients receiving immunomodulators. In 436 immunosuppressed solid organ transplant recipients, 17% developed anti-S1 antibodies by 14-21 days following a single dose of mRNA vaccine, although there was no control group. 6 Geisen et al. evaluated antibody responses following the second dose of mRNA vaccines in 42 controls and 26 patients with IMIDs, including psoriasis (n = 4), psoriatic arthritis (n = 2) and rheumatoid arthritis (n = 8), and others receiving biologics, conventional disease-modifying agents and/or prednisolone. They showed reduced anti-S IgG titres and SARS-CoV-2 neutralization in patients receiving immunomodulators, but no difference between those receiving tumour necrosis factor inhibitors and nonbiologic immunomodulators. However, all 26 participants receiving immunomodulators had IgG antibodies above the assay cutoff. 7 Our data show that not all patients on immunomodulators mount a detectable humoral response after a single dose of the BNT162b2 or AZD1222 vaccines and might therefore remain susceptible to COVID-19. Strengths of our study are the utilization of two assays and controlling for a range of confounders. Limitations include the lack of a control IMID group not receiving an immunomodulator, and the modest sample size, resulting in wide CIs for some ORs and preventing subgroup analysis of drug types. Further controlled studies examining antibody titres following dosing of both vaccines are required, along with studies to define titres that correspond with protection. The data are presented as the number (%) of patients testing positive or negative, unless stated otherwise. a Biologics included abatacept (1), adalimumab (29), brodalumab (3), certolizumab (2), etanercept (2), guselkumab (6), ixekizumab (7), risankizumab (4), secukinumab (6), tildrakizumab (1) and ustekinumab (20). Oral immunomodulators included apremilast (2), ciclosporin (2), dimethyl fumarate (7), methotrexate (16), methotrexate and tofacitinib combined (1) and prednisolone (3) . Combinations of treatment included the following: apremilast and guselkumab (1), azathioprine and infliximab (1), dimethyl fumarate and guselkumab (1), methotrexate and adalimumab (1), methotrexate and etanercept (1), methotrexate and rituximab (1), methotrexate and ustekinumab (2) . b Prior infection as diagnosed by Elecsys nucleocapsid assay. c The models excluded those with prior infection (n = 22). Confounders or covariates included age (continuous), sex, vaccine type and number days from vaccine dose to antibody test (continuous).

Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals

T-cell and antibody responses to first BNT162b2 vaccine dose in previously SARS-CoV-2-infected and infection-naive UK healthcare workers: a multicentre, prospective, observational cohort study

T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates

Antibody responses after a single dose of SARS-CoV-2 mRNA vaccine

Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients

Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort

Funding sources: This study was

Valeant, Schering-Plough (now MSD) and UCB