Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients

Rheumatology (Oxford). 2007 Feb;46(2):327-34. doi: 10.1093/rheumatology/kel236. Epub 2006 Jul 31.

Abstract

Objective: To evaluate the rate of infections in rheumatic patients treated with tumour necrosis factor (TNF)-alpha blockers in daily practice and to determine potential risk factors of infections.

Methods: Systematic retrospective study was conducted in a tertiary-referral centre of all patients receiving at least one TNF-alpha blocker, between 1997 and December 2004. Serious infections were defined as life-threatening, requiring hospitalization or sequelae. The incidence of infections during the first TNF-alpha blocker course was compared with the incidence during the period just before such therapy, in the same patients and a number needed to harm was calculated. Univariate and multivariate analysis between patients who suffered from at least one infection during treatment or not, was conducted in order to determine potential associated risk factors.

Results: Among the 709 patients treated with at least one TNF-alpha blocker, 57.7% had rheumatoid arthritis; a total of 275 infectious events in 245 patients (34.5%) were reported during all treatment courses. Among these infections, 47 infections in 44 patients (6.2%) fulfilled the definition of serious infections. The incidence rate of serious infections was 3.4 +/- 38.7 per 100 patient-yrs before TNF-alpha blocker therapy vs 10.5 +/- 86.9 during the first TNF-alpha blocker course (P = 0.03, number needed to harm = 14). The single risk factor picked up by multivariate analysis to explain infections was previous joint surgery [odds ratio (OR) = 2.07, 95% confidence interval (CI) = (1.43-2.98), P < 0.0001] and, if surgery was taken out of the model, the cumulative dose of steroids [OR = 1.28 (1.04-1.59), P = 0.02].

Conclusion: The rate of serious infections during TNF-alpha blocker treatment observed in daily practice conditions was much higher than in phase III trials evaluating TNF-alpha blockers. Serious infections are frequent in daily practice and close monitoring is required.

MeSH terms

  • Adalimumab
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects*
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects
  • Immunologic Factors / adverse effects*
  • Infliximab
  • Male
  • Middle Aged
  • Opportunistic Infections / chemically induced*
  • Receptors, Tumor Necrosis Factor
  • Respiratory Tract Infections / chemically induced
  • Retrospective Studies
  • Rheumatic Diseases / drug therapy*
  • Risk Factors
  • Skin Diseases, Infectious / chemically induced
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Immunologic Factors
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept