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Rheumatology (Oxford). 2019 Sep 1;58(9):1585-1596. doi: 10.1093/rheumatology/kez045.

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

Author information

Department of Public Health/Division of Infectious Diseases, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Rheumatology, University Hospital Basel, Basel.
Department of Rheumatology, Immunology and Allergology, University Hospital of Bern, Bern.
Division of Rheumatology, Department of Internal Medicine, Cantonal Hospital St Gallen, St Gallen.
Department of Rheumatology, University Hospital of Zurich, Zurich.
Division of Rheumatology, University Medical Department, Cantonal Hospital Aarau, Aarau.
Department of Medicine, Division of Rheumatology, University Hospitals of Geneva, Geneva.
Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich.
Department of Medicine and Diagnostics, Swiss Tropical and Public Health Institute.
University of Basel, Basel, Switzerland.
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
Center for Vaccinology, University Hospital and Faculty of Medicine, Geneva, Switzerland.



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).


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.


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.


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:,, Identifier: NCT01947465.


diphtheria vaccination; immunogenicity; immunosuppression; rheumatic disease; safety; tetanus vaccination

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