title: Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT.
abstract: BACKGROUND
  We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs).
  
  
  METHODS
  The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis).
  
  
  RESULTS
  A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFalpha agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFalpha: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFalpha agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFalpha vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFalpha agents (P = 1.0).
  
  
  CONCLUSIONS
  No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.
authors.affiliation: German Rheumatism Research Centre Berlin, a Leibniz institute, Charitéplatz 1, 10117 Berlin, Germany. Strangfeld@drfz.de
authors.forename: Anja
authors.initials: A
authors.lastname: Strangfeld
authors.forename: Franka
authors.initials: F
authors.lastname: Hierse
authors.forename: Rolf
authors.initials: R
authors.lastname: Rau
authors.forename: Gerd-Ruediger
authors.initials: GR
authors.lastname: Burmester
authors.forename: Brigitte
authors.initials: B
authors.lastname: Krummel-Lorenz
authors.forename: Winfried
authors.initials: W
authors.lastname: Demary
authors.forename: Joachim
authors.initials: J
authors.lastname: Listing
authors.forename: Angela
authors.initials: A
authors.lastname: Zink
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D005858:Germany; D006801:Humans; D015994:Incidence; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced / Q000453:epidemiology*; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D012042:Registries; D012307:Risk Factors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D053590:Interleukin 1 Receptor Antagonist Protein