From Wiley via Jisc Publications RouterHistory: received 2021-04-13, rev-recd 2021-05-06, accepted 2021-05-08, pub-electronic 2021-06-04Article version: VoRPublication status: PublishedFunder: Psoriasis Association; Id: http://dx.doi.org/10.13039/10001312

Al‐Janabi, A.

Chinoy, H.

Griffiths, C.E.M.

Hunter, H.J.A.

Littlewood, Z.

Moriarty, C.

Warren, R.B.

Yiu, Z.Z.N.

ChesterRep

Research letterAntibody responses to single-dose SARS-CoV-2vaccination in patients receivingimmunomodulators for immune-mediatedinflammatory diseaseDOI: 10.1111/bjd.20479DEAR EDITOR, There are few data on whether immunomodula-tory therapy attenuates humoral response to vaccines for sev-ere acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Some vaccines require two doses for maximum protection,with international variation in dosing schedules. A 3-monthinterval between doses is being used in the UK. We evaluatedantibody titres to SARS-CoV-2 following initial-doseBNT162b2 (Pfizer/BioNTech) or AZD1222 (AstraZeneca) vac-cines in adults with psoriasis and other immune-mediatedinflammatory diseases (IMIDs) receiving biologic and/or oralnonbiologic immunomodulators.Participants were recruited from Salford Royal NHS Foun-dation Trust. Blood samples were collected 2–12 weeks afterthe first vaccine dose. Total antibodies against SARS-CoV-2spike protein S1 receptor-binding domain were quantifiedusing the Roche Elecsys Anti-SARS-CoV-2 S immunoassay(Roche Diagnostics Limited, Burgess Hill, UK) and anti-S1IgG was measured using the Siemens SARS-CoV-2 IgGimmunoassay (sCOVG) (Siemens, Munich, Germany). TheElecsys Anti-SARS-CoV-2 immunoassay, which detects anti-bodies against the nucleocapsid antigen absent from vaccines,identified those with prior infection. Two multivariable logis-tic regression models, excluding patients with prior SARS-CoV-2 infection (n = 22), were created with positive or neg-ative Elecsys anti-S1 and sCOVG assays as outcome variables,medication category as the exposure and a priori confounders(Table 1). The study was approved by the London-SurreyBorders Research Ethics Committee and Health ResearchAuthority.In total 120 participants with IMIDs were recruited, includ-ing psoriasis (n = 107), psoriatic arthritis (n = 25), rheuma-toid arthritis (n = 10), systemic lupus erythematosus (n = 1)and Crohn disease (n = 3); some patients had more than onecondition. The median age was 53 years (interquartile range33–73) and the ethnicities of the recruited participantsincluded white (n = 111) and Asian (n = 9). The median timefrom vaccination to venepuncture was 34 days (interquartilerange 23–46). Our data show that 15% of patients with IMIDsreceiving immunomodulators failed to mount a detectableantibody response to the single-dose BNT162b2 or AZD1222vaccines; 41% had no detectable anti-S1 IgG. Anti-SARS-CoV-2S appears more sensitive than the sCOVG assay. Nonbiologicimmunomodulators, for example methotrexate, reduced theodds of a detectable antibody response compared with biolog-ics: adjusted odds ratio (OR) 031 [95% confidence interval(CI) 008–117] and OR 018 (95% CI 006–059) for theElecsys 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 afterthe first vaccine dose, as measured by Roche Elecsys Anti-SARS-CoV-2 S or other spike-antigen-specific assays detectingIgG and total immunoglobulin.1–5 No similar data for thesCOVG assay are available.All of our participants with prior COVID-19 had antibod-ies detected by both assays after a single vaccination, in linewith previous observations.1,2 Increasing age was also associ-ated nonlinearly with reduced odds of a positive antibodyresponse: OR 012 (95% CI 003–046) and OR 012 (95%CI 004–039) for the Elecsys Anti-SARS-CoV-2 S andsCOVG assays, respectively, in those aged 60 years and overcompared with those aged below 60 years, in a separatepost hoc analysis. This is consistent with phase I trial datafor the BNT162b2 vaccine,4 and may be due to immunose-nescence.There have been few other studies examining the humoralresponse to SARS-CoV-2 vaccines in patients receivingimmunomodulators. In 436 immunosuppressed solid organtransplant recipients, 17% developed anti-S1 antibodies by14–21 days following a single dose of mRNA vaccine,although there was no control group.6 Geisen et al. evaluatedantibody responses following the second dose of mRNA vac-cines in 42 controls and 26 patients with IMIDs, includingpsoriasis (n = 4), psoriatic arthritis (n = 2) and rheumatoidarthritis (n = 8), and others receiving biologics, conventionaldisease-modifying agents and/or prednisolone. They showedreduced anti-S IgG titres and SARS-CoV-2 neutralization inpatients receiving immunomodulators, but no differencebetween those receiving tumour necrosis factor inhibitorsand nonbiologic immunomodulators. However, all 26 partici-pants receiving immunomodulators had IgG antibodies abovethe assay cutoff.7Our data show that not all patients on immunomodulatorsmount a detectable humoral response after a single dose ofthe BNT162b2 or AZD1222 vaccines and might thereforeremain susceptible to COVID-19. Strengths of our study arethe utilization of two assays and controlling for a range of© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021) 1This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use,distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.confounders. Limitations include the lack of a control IMIDgroup not receiving an immunomodulator, and the modestsample size, resulting in wide CIs for some ORs and prevent-ing subgroup analysis of drug types. Further controlled studiesexamining antibody titres following dosing of both vaccinesare required, along with studies to define titres that corre-spond with protection.Acknowledgments: We would like to thank the DISCOVERGroup for their contribution to the study design, includingProfessor John McLaughlin, Professor Ian Bruce, Professor AnneBarton, Professor Jimmy Limdi and Professor Kimme Hyrich.A.A. is a Medical Research Council Clinical Research Fellow.C.E.M.G. is a National Institute for Health Research (NIHR)Emeritus Senior Investigator. H.C. and R.B.W. are supported bythe NIHR Manchester Biomedical Research Centre FundingScheme. Z.Z.N.Y. is an NIHR-funded clinical lecturer.A. Al-Janabi iD ,1 Z. Littlewood,1 C.E.M. Griffiths iD ,1 H.J.A.Hunter,1 H. Chinoy iD ,2,3,4 C. Moriarty,5 Z.Z.N. Yiu iD 1 andR.B. Warren iD 11Dermatology Centre, Salford Royal NHS Foundation Trust, ManchesterNIHR Biomedical Research Centre, The University of Manchester,Manchester, M6 8HD, UK; 2National Institute for Health Research,Manchester Biomedical Research Centre, Manchester University NHSFoundation Trust, The University of Manchester, Manchester, UK;3Department of Rheumatology, Salford Royal NHS Foundation Trust,Manchester Academic Health Science Centre, Salford, UK; 4Centre forMusculoskeletal Research, Faculty of Biology, Medicine and Health, TheTable 1 Multivariable logistic regression and characteristics of 120 recruited participants by humoral response to SARS-CoV-2 vaccinationElecsys SARS-CoV-2 S (Roche) sCOVG (Siemens) IgGPos. (≥ 08 U mL1) Neg. (< 08 U mL1) Pos. (≥ 1 U mL1) Neg. (< 1 U mL1)Total 102 (85) 18 (15) 71 (59) 49 (41)Drug classaBiologic 73 (90) 8 (10) 55 (68) 26 (32)Oral immunomodulator 23 (74) 8 (26) 10 (32) 21 (68)Biologic and oral immunomodulator 6 (75) 2 (25) 6 (75) 2 (25)SexMale 60 (85) 11 (15) 44 (62) 27 (38)Female 42 (86) 7 (14) 27 (55) 22 (45)Age (years)18–39 21 (100) 0 (0) 17 (81) 4 (19)40–59 56 (89) 7 (11) 42 (67) 21 (33)≥ 60 25 (69) 11 (31) 12 (33) 24 (67)VaccineBNT162b2 55 (92) 5 (8) 39 (65) 21 (35)AZD1222 47 (78) 13 (21) 32 (53) 28 (47)Time from vaccine (days)0–28 37 (74) 13 (26) 29 (58) 21 (42)≥ 29 65 (93) 5 (7) 42 (60) 28 (40)Prior SARS-CoV-2b 22 (100) 0 (0) 22 (100) 0 (0)No prior SARS-CoV-2 80 (82) 18 (18) 49 (50) 49 (50)Logistic regression models (n = 98),c odds ratio (95% confidence interval)Drug classa Elecsys SARS-CoV-2 S assay sCOVG IgG assayBiologic Reference ReferenceOral immunomodulator Not adjusted 030 (010–091) 015 (005–044)Adjusted 031 (008–117) 018 (006–059)Biologic and oral immunomodulator Not adjusted 013 (002–108) 062 (008–467)Adjusted 006 (001–080) 061 (007–532)The data are presented as the number (%) of patients testing positive or negative, unless stated otherwise. aBiologics 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). bPrior infection as diagnosed by Elec-sys nucleocapsid assay. cThe 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).© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021)2 Research letterUniversity of Manchester, Manchester, UK; and 5Affinity Biomarker Labs,Translation & Innovation Hub Building, Imperial College London White CityCampus, London, W12 0BZ, UKCorrespondence: Richard B. Warren.Email: richard.warren@manchester.ac.ukReferences1 Manisty C, Otter AD, Treibel TA et al. Antibody response to firstBNT162b2 dose in previously SARS-CoV-2-infected individuals. Lan-cet 2021; 397:1057–8.2 Angyal A, Longet S, Moore S et al. T-cell and antibody responses tofirst BNT162b2 vaccine dose in previously SARS-CoV-2-infectedand infection-naive UK healthcare workers: a multicentre, prospec-tive, observational cohort study. Available at: https://doi.org/10.2139/ssrn.3812375 (preprint).3 Ewer KJ, Barrett JR, Belij-Rammerstorfer S et al. T cell and antibodyresponses induced by a single dose of ChAdOx1 nCoV-19(AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med 2020;27:270–8.4 Walsh EE, Frenck RW, Falsey AR et al. Safety and immunogenicityof two RNA-based Covid-19 vaccine candidates. N Engl J Med 2020;383:2439–50.5 Bradley T, Grundberg E, Selvarangan R et al. Antibody responsesafter a single dose of SARS-CoV-2 mRNA vaccine. N Engl J Med2021; 384:1959–61. https://doi.org/10.1056/NEJMc21020516 Boyarsky BJ, Werbel WA, Avery RK et al. Immunogenicity of a sin-gle dose of SARS-CoV-2 messenger RNA vaccine in solid organtransplant recipients. JAMA 2021; 325:1784–6.7 Geisen UM, Berner DK, Tran F et al. Immunogenicity and safety ofanti-SARS-CoV-2 mRNA vaccines in patients with chronic inflam-matory conditions and immunosuppressive therapy in a monocen-tric cohort. Ann Rheum Dis 2021; in press; https://doi.org/10.1136/annrheumdis-2021-220272Funding sources: This study was funded by a grant from the PsoriasisAssociation.Conflicts of interest: C.E.M.G. has acted as a consultant and/or speakerfor AbbVie, Almirall, Amgen, BMS, Boehringer, Celgene, Eli Lilly,Janssen, LEO Pharma, Pfizer, Novartis, Sun Pharma and UCB. H.J.A.H.has acted as a consultant and/or speaker for Janssen, AbbVie, Pfizer,UCB, Sanofi Genzyme, Novartis, Almirall, Eli Lilly and LEO Pharma.H.C. has acted as a consultant and/or speaker for AbbVie, Novartis,UCB, Lilly, Biogen and Orphazyme. C.M. is an employee of AffinityBiomarker Labs. R.B.W. has acted as a consultant and/or speaker forAbbVie, Almirall, Amgen, Boehringer, Celgene, Eli Lilly, Janssen, LEOPharma, Medac, Novartis, Pfizer, Sun Pharma, Valeant, Schering-Plough (now MSD) and UCB. The other authors declare they have noconflicts of interest.© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021)Research letter 3

Antibody responses to single‐dose SARS‐CoV‐2 vaccination in patients receiving immunomodulators for immune‐mediated inflammatory disease

https://chesterrep.openrepository.com/bitstream/handle/10034/624838/bjd.20479.pdf?sequence=3&isAllowed=y

Antibody responses to single‐dose SARS‐CoV‐2 vaccination in patients receiving immunomodulators for immune‐mediated inflammatory disease

Abstract

Similar works

Full text

Available Versions

ChesterRep