Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT

Arthritis Res Ther. 2010;12(1):R5. doi: 10.1186/ar2904. Epub 2010 Jan 8.

Abstract

Introduction: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / adverse effects*
  • Case-Control Studies
  • Female
  • Germany
  • Humans
  • Incidence
  • Interleukin 1 Receptor Antagonist Protein / adverse effects*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / chemically induced
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology*
  • Registries
  • Risk Factors

Substances

  • Antirheumatic Agents
  • Biological Products
  • Interleukin 1 Receptor Antagonist Protein