Detection and evaluation of a drug safety signal concerning pancreatic cancer: lessons from a joint approach of three European biologics registers

Rheumatology (Oxford). 2011 Jan;50(1):146-51. doi: 10.1093/rheumatology/keq301. Epub 2010 Sep 22.

Abstract

Objectives: A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the national biologics registers in the UK and Sweden was performed.

Methods: Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers.

Results: Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden.

Conclusion: The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / adverse effects*
  • Biomarkers
  • Cohort Studies
  • Female
  • Germany
  • Humans
  • Isoxazoles / adverse effects*
  • Leflunomide
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / chemically induced*
  • Registries / standards*
  • Risk Factors
  • Sweden
  • United Kingdom
  • White People

Substances

  • Antirheumatic Agents
  • Biological Products
  • Biomarkers
  • Isoxazoles
  • Leflunomide