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Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient?
  1. A Strangfeld1,
  2. M Eveslage1,
  3. M Schneider2,
  4. H J Bergerhausen3,
  5. T Klopsch4,
  6. A Zink1,5,
  7. J Listing1
  1. 1Programmbereich Epidemiologie, Deutsches Rheuma-Forschungszentrum Berlin, ein Leibniz Institut, Berlin, Germany
  2. 2Klinik fuer Endokrinologie, Diabetologie und Rheumatologie, Heinrich-Heine-Universitaet Duesseldorf, Duesseldorf, Germany
  3. 3Klinik fuer Rheumatologie, Wedau Kliniken, Klinikum Duisburg, Duisburg, Germany
  4. 4Rheumatologist in private practice, Neubrandenburg, Germany
  5. 5Klinik fuer Rheumatologie und Klinische Immunologie, Charité Universitaetsmedizin Berlin, Berlin, Germany
  1. Correspondence to Dr A Strangfeld, Programmbereich Epidemiologie, Deutsches Rheuma-Forschungszentrum Berlin, ein Leibniz Institut, Charitéplatz 1, 10117 Berlin, Germany; strangfeld{at}


Objective To examine the risk of serious infection conveyed by tumour necrosis factor α (TNFα) inhibitors in the treatment of rheumatoid arthritis (RA).

Methods Data from patients with RA enrolled in the German biologics register RABBIT were used for analysis. Baseline patient characteristics, time-varying risk factors (treatment changes, functional capacity) and selection processes caused by dropout, death or switching to non-anti-TNF treatment were taken into account to estimate the adjusted incidence rate ratios (IRRadj) of serious infection during treatment with TNF inhibitors compared with non-biological disease-modifying antirheumatic drug treatment.

Results Data were available on 5044 patients, in whom 392 serious infections occurred. The crude rates of serious infections in patients treated with TNF inhibitors declined over the first 3 years of observation (from 4.8 to 2.2/100 patient-years). This decline was driven by (1) treatment termination or loss to follow-up in patients at increased risk and (2) a risk reduction through decreasing glucocorticoid doses and improvement in function. Adjusted for selection processes and time-varying risk factors, the following parameters assessed at baseline (age, chronic diseases) or at follow-up prior to the infection were significantly associated with an increased risk: age >60 years, chronic lung or renal disease, low functional capacity, history of serious infections, treatment with glucocorticoids (7.5–14 mg/day, IRRadj 2.1 (95% CI 1.4 to 3.2); ≥15 mg/day, IRRadj 4.7 (95% CI 2.4 to 9.4)) and treatment with TNFα inhibitors (IRRadj 1.8 (95% CI 1.2 to 2.7)).

Conclusion Reasons for the decline in infection rates observed at the group level were identified. The results enable expected infection rates to be calculated in individual patients based on their risk profiles.

This paper is freely available online under the BMJ Journals unlocked scheme, see

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  • Funding RABBIT has been supported by an unconditional joint grant from Essex Pharma/MSD (since 2001), Wyeth Pharma/Pfizer (since 2001), Amgen (2003–8), Swedish Orphan Biovitrum (since 2009) and Abbott (since 9/2003). Since 2007 it has also been supported by Bristol-Myers Squibb and Roche. Since 2009 it has received support from UCB. The principal investigators and their team have full academic freedom in study design and conduct, data analysis and publication of results. These stipulations are delineated in their contract with the sponsors. However, for the purposes of information, all seven funding companies receive every manuscript 30 days prior to submission. The data interpretation, drafting, critical revision and approval of the final manuscript were performed solely by the authors.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was approved in 2001 by the ethics committee of the Charité University Medicine, Berlin.

  • Provenance and peer review Not commissioned; externally peer reviewed.