Risk of mortality, fatal infection, and fatal malignancy related to use of anti-tumor necrosis factor-α biologics by rheumatoid arthritis patients

Semin Arthritis Rheum. 2012 Dec;42(3):223-33. doi: 10.1016/j.semarthrit.2012.05.004. Epub 2012 Jun 28.

Abstract

Objective: To estimate rates of all-cause mortality, fatal infection, and fatal malignancy in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor-α (anti-TNF) biologics.

Methods: A retrospective cohort study of RA patients initiating therapy with adalimumab, etanercept, or infliximab from January 2000 to December 2008 was conducted using an administrative database of a large health care insurer. Patients were followed for the occurrence of fatal events, which were identified using the National Death Index database. Overall and anti-TNF biologic-stratified incidence rates per 1000 person-years were calculated. Primary analyses were time-on-drug based on current anti-TNF biologic exposure on the outcome date for fatal infection and intent-to-treat based on the anti-TNF biologic initiated at cohort entry for fatal malignancy.

Results: Seven thousand seven hundred thirty-four patients initiated an anti-TNF biologic with 13,296 person-years of observation. Seventy-one deaths were identified, including 12 fatal infections and 21 fatal malignancies. The all-cause mortality rate was 5.34 per 1000 person-years. Incidence rates for fatal infection were similar among anti-TNF biologic current exposure groups (0.78 to 0.88 per 1000 person-years). Incidence rates for fatal malignancy were similar among anti-TNF biologic initiator groups (1.24 to 1.84 per 1000 person-years).

Conclusions: The all-cause mortality rate in RA patients treated with anti-TNF biologics was lower than in previous studies in similar non-US populations, but comparable to mortality rates in the US general population. Fatal infection and fatal malignancy rates were similar across anti-TNF biologic groups. Further studies, designed to detect risk differences associated with anti-TNF biologic use and baseline risk factors, would provide additional information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / mortality*
  • Bacterial Infections / etiology
  • Bacterial Infections / mortality*
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects
  • Infliximab
  • Male
  • Middle Aged
  • Neoplasms / etiology
  • Neoplasms / mortality*
  • Receptors, Tumor Necrosis Factor
  • Retrospective Studies
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • United States / epidemiology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept