Infections in patients treated with tumor necrosis factor antagonists: incidence, etiology and mortality in the BIOBADASER registry

Med Clin (Barc). 2011 Nov 12;137(12):533-40. doi: 10.1016/j.medcli.2010.11.032. Epub 2011 Apr 22.


Background and objectives: Whether the use of tumor necrosis factor antagonists increases the risk of infection remains a subject of open debate. Developing effective strategies of prevention and empirical treatment entails carefully establishing the etiology and prognosis of the infections.

Patients and methods: Analysis of the Spanish registry BIOBADASER (Feb-2000 to Jan-2006), a national drug safety registry of patients with rheumatic diseases.

Results: 907 episodes of infection occurring in 6,969 patients were analyzed. The infection incidence observed was 53.09 cases/1,000 patients-years (CI 95% 49.69-56.66). The most frequent infections were skin infection (12.18 cases/1,000 patients-yrs), pneumonia (5.97 cases/1,000 patients-yrs), cystitis (3.92 cases/1,000 patients-yrs), tuberculosis (3.51 cases/1,000 patients-yrs) and arthritis (3.76 cases/1,000 patients-yrs). Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa and Salmonella spp. emerged as important pathogens. Varicella zoster virus and Herpes simplex virus caused most cases of viral infections. Mucocutaneous candidiasis accounted for most fungal infections. Mortality was increased in infected patients (log-rank test p<0.0001). Pneumonia, sepsis, tuberculosis, abdominal infection and endocarditis were associated with significant attributable mortality.

Conclusions: A significant number of bacterial, viral and fungal infections occurred in patients with rheumatic diseases treated with TNF antagonists. The information of this study can illuminate clinicians globally on how to address infection in this vulnerable group of patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Infectious / epidemiology
  • Arthritis, Infectious / etiology
  • Bacterial Infections / epidemiology
  • Bacterial Infections / etiology*
  • Cohort Studies
  • Disease Susceptibility
  • Follow-Up Studies
  • Humans
  • Immunocompromised Host
  • Incidence
  • Kaplan-Meier Estimate
  • Leishmaniasis / epidemiology
  • Leishmaniasis / etiology
  • Mycoses / epidemiology
  • Mycoses / etiology*
  • Registries
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / etiology
  • Rheumatic Diseases / drug therapy
  • Sepsis / epidemiology
  • Sepsis / etiology
  • Skin Diseases, Infectious / epidemiology
  • Skin Diseases, Infectious / etiology
  • Spain / epidemiology
  • Tuberculosis / epidemiology
  • Tuberculosis / etiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Urinary Tract Infections / epidemiology
  • Urinary Tract Infections / etiology
  • Virus Diseases / epidemiology
  • Virus Diseases / etiology*


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha