Malignancies and anti-TNF therapy in rheumatoid arthritis: a single-center observational cohort study

Clin Rheumatol. 2015 Oct;34(10):1687-95. doi: 10.1007/s10067-015-3026-7. Epub 2015 Jul 30.

Abstract

Inhibitors of tumor necrosing factor alpha (TNF-a) have proven to be highly effective in the treatment of rheumatoid arthritis (RA). Concerns, however, are raised about the possible association between these treatments and an increased development of malignancies. The objective of this paper was to compare the risk of hematologic and solid malignancies in patients treated for RA with anti-TNF therapy, with the risk in the general population. From January 2000 until January 2012, all RA patients that started treatment with anti-TNF agents were included in this single-center cohort study. The primary outcome of this study was the incidence of malignancy after starting anti-TNF treatment. In our cohort of 365 patients, 34 malignancies were discovered in 30 patients after the start of anti-TNF treatment; 20 patients developed a solid malignancy, 6 a hematologic, 2 a solid and a hematologic malignancy, and 2 patients developed 2 solid malignancies. The overall incidence rate (IR) of malignancy was 1379.1 per 100.000 patient years. The risk or standardized incidence ratio (SIR) of solid malignancy, calculated by comparison with the age-adjusted population in Flanders, was 120.1 in female and 136.7 in male patients. The calculated SIR of hematologic malignancy was 450.8 for women and 473.9 for men. Some immune modulation-related lymphoproliferative disorders regressed spontaneously when stopping TNF blockers. Overall, the malignancy risk in our rheumatoid arthritis patients treated with anti-TNF therapy was slightly higher than in the normal population; the risk of hematologic malignancies was more important.

Keywords: Cyclic citrullinated peptide; Malignancies; Rheumatoid arthritis; TNF-a.

Publication types

  • Observational Study

MeSH terms

  • Adalimumab / adverse effects
  • Adalimumab / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / drug therapy*
  • Comorbidity
  • Etanercept / adverse effects
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Incidence
  • Infliximab / adverse effects
  • Infliximab / therapeutic use
  • Lymphoproliferative Disorders
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / drug therapy*
  • Prospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept