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

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


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:,, Identifier: NCT01947465.

Keywords: diphtheria vaccination; immunogenicity; immunosuppression; rheumatic disease; safety; tetanus vaccination.

Publication types

  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial / biosynthesis*
  • Clostridium tetani / immunology
  • Corynebacterium diphtheriae / immunology
  • Diphtheria / prevention & control
  • Diphtheria-Tetanus Vaccine / adverse effects*
  • Diphtheria-Tetanus Vaccine / immunology
  • Female
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine / drug effects*
  • Immunogenicity, Vaccine / immunology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Prospective Studies
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / immunology*
  • Tetanus / prevention & control
  • Vaccination
  • Young Adult


  • Antibodies, Bacterial
  • Diphtheria-Tetanus Vaccine
  • Immunosuppressive Agents

Associated data