Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases-a prospective multi-centre cohort study

TY - JOUR

T1 - Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases-a prospective multi-centre cohort study

AU - Bühler, Silja

AU - Jaeger, Veronika Katharina

AU - Adler, Sabine

AU - Bannert, Bettina

AU - Brümmerhoff, Carolin

AU - Ciurea, Adrian

AU - Distler, Oliver

AU - Franz, Juliane

AU - Gabay, Cem

AU - Hagenbuch, Niels

AU - Herzog, Christian

AU - Hasler, Paul

AU - Kling, Kerstin

AU - Kyburz, Diego

AU - Müller, Rüdiger

AU - Nissen, Michael John

AU - Siegrist, Claire-Anne

AU - Villiger, Peter Matthias

AU - Walker, Ulrich A

AU - Hatz, Christoph

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - OBJECTIVES: We aimed to assess the safety and immunogenicity of a diphtheria/tetanus vaccine booster dose in three different patient groups with rheumatic diseases on a variety of immunosuppressive/immunomodulatory medications compared with healthy controls (HCs).METHODS: We conducted a multi-centre prospective cohort study in Switzerland. We enrolled patients with RA, axial SpA/PsA, vasculitis (Behçet's disease, ANCA-associated vasculitis) and HCs. Diphtheria/tetanus vaccination was administered according to the Swiss vaccination recommendations. Blood samples were drawn before vaccination, and 1 month and 3 months afterwards. Antibody concentrations against vaccine antigens were measured by ELISA. Immunogenicity was compared between patient and medication groups. A mixed model was applied for multivariate analysis. Missing data were dealt with using multiple imputation.RESULTS: Between January 2014 and December 2015, we enrolled 284 patients with rheumatic diseases (131 RA, 114 SpA/PsA, 39 vasculitis) and 253 HCs. Of the patients, 89% were on immunosuppressive/immunomodulatory medication. Three months post-vaccination 100% of HCs vs 98% of patients were protected against tetanus and 84% vs 73% against diphtheria. HCs and SpA/PsA patients had significantly higher responses than RA and vasculitis patients. Assessing underlying diseases and medications in a multivariate model, rituximab was the only factor negatively influencing tetanus immunogenicity, whereas only MTX treatment had a negative influence on diphtheria antibody responses. No vaccine-related serious adverse events were recorded.CONCLUSION: Diphtheria/tetanus booster vaccination was safe. Tetanus vaccination was immunogenic; the diphtheria component was less immunogenic. Vaccine responses were blunted by rituximab and MTX.TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, Identifier: NCT01947465.

AB - OBJECTIVES: We aimed to assess the safety and immunogenicity of a diphtheria/tetanus vaccine booster dose in three different patient groups with rheumatic diseases on a variety of immunosuppressive/immunomodulatory medications compared with healthy controls (HCs).METHODS: We conducted a multi-centre prospective cohort study in Switzerland. We enrolled patients with RA, axial SpA/PsA, vasculitis (Behçet's disease, ANCA-associated vasculitis) and HCs. Diphtheria/tetanus vaccination was administered according to the Swiss vaccination recommendations. Blood samples were drawn before vaccination, and 1 month and 3 months afterwards. Antibody concentrations against vaccine antigens were measured by ELISA. Immunogenicity was compared between patient and medication groups. A mixed model was applied for multivariate analysis. Missing data were dealt with using multiple imputation.RESULTS: Between January 2014 and December 2015, we enrolled 284 patients with rheumatic diseases (131 RA, 114 SpA/PsA, 39 vasculitis) and 253 HCs. Of the patients, 89% were on immunosuppressive/immunomodulatory medication. Three months post-vaccination 100% of HCs vs 98% of patients were protected against tetanus and 84% vs 73% against diphtheria. HCs and SpA/PsA patients had significantly higher responses than RA and vasculitis patients. Assessing underlying diseases and medications in a multivariate model, rituximab was the only factor negatively influencing tetanus immunogenicity, whereas only MTX treatment had a negative influence on diphtheria antibody responses. No vaccine-related serious adverse events were recorded.CONCLUSION: Diphtheria/tetanus booster vaccination was safe. Tetanus vaccination was immunogenic; the diphtheria component was less immunogenic. Vaccine responses were blunted by rituximab and MTX.TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, Identifier: NCT01947465.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Bacterial/biosynthesis

KW - Clostridium tetani/immunology

KW - Corynebacterium diphtheriae/immunology

KW - Diphtheria/prevention & control

KW - Diphtheria-Tetanus Vaccine/adverse effects

KW - Female

KW - Humans

KW - Immunization, Secondary

KW - Immunogenicity, Vaccine/drug effects

KW - Immunosuppressive Agents/pharmacology

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Rheumatic Diseases/drug therapy

KW - Tetanus/prevention & control

KW - Vaccination

KW - Young Adult

U2 - 10.1093/rheumatology/kez045

DO - 10.1093/rheumatology/kez045

M3 - SCORING: Journal article

C2 - 30877773

VL - 58

SP - 1585

EP - 1596

JO - RHEUMATOLOGY

JF - RHEUMATOLOGY

SN - 1462-0324

IS - 9

ER -