title: Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis.
abstract: OBJECTIVE
  This project was undertaken to assess the risk of malignancy in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors (TNFi) in clinical practice, as recorded in prospective, observational studies.
  
  
  METHODS
  The authors undertook comprehensive searches of MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and American College of Rheumatology, European League against Rheumatism and British Society for Rheumatology conference abstracts according to a prespecified protocol.
  
  
  RESULTS
  The searches identified 2039 full-text papers and 1979 conference abstracts, of which 21 full texts and eight abstracts met the inclusion criteria. The pooled estimate for the risk of all-site malignancy from seven studies was 0.95 (95% CI 0.85 to 1.05). Two studies reported there was no evidence that longer exposure to TNFi agents increased the risk of malignancy. In patients with previous malignancies there was a higher risk of a new/recurring malignancy. This risk was not increased further by exposure to TNFi, although CI were wide. Results from four studies showed that patients treated with TNFi have a significantly increased risk of developing a non-melanoma skin cancer (1.45, 95% CI 1.15 to 1.76). In addition, patients are at an increased risk of developing melanoma, as the pooled estimate from two studies was 1.79 (95% CI 0.92 to 2.67). The pooled estimate for the risk of lymphoma was 1.11 (95% CI 0.70 to 1.51).
  
  
  CONCLUSIONS
  This systematic review and meta-analysis shows that TNFi treatments do not increase the risk of malignancy, particularly lymphoma. However, they do appear to increase the risk of skin cancer, including melanoma.
authors: Hôpital Bicêtre, Institut Pour la Santé et Recherche Médicale (INSERM) U 1012, Université Paris-Sud 11, Le Kremlin Bicêtre, France. xavier.mariette@bct.aphp.fr
authors: Xavier
authors: X
authors: Mariette
authors: Marco
authors: M
authors: Matucci-Cerinic
authors: Karel
authors: K
authors: Pavelka
authors: Peter
authors: P
authors: Taylor
authors: Ronald
authors: R
authors: van Vollenhoven
authors: Rebecca
authors: R
authors: Heatley
authors: Claire
authors: C
authors: Walsh
authors: Richard
authors: R
authors: Lawson
authors: Alan
authors: A
authors: Reynolds
authors: Paul
authors: P
authors: Emery
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects*; D001168:Arthritis / Q000188:drug therapy* / Q000453:epidemiology; D004812:Epidemiologic Methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008223:Lymphoma / Q000139:chemically induced; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D012042:Registries; D012878:Skin Neoplasms / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha