Risk of Subsequent Infection Among Patients Receiving Tumor Necrosis Factor Inhibitors and Other Disease-Modifying Antirheumatic Drugs

Arthritis Rheumatol. 2016 Jan;68(1):67-76. doi: 10.1002/art.39416.

Abstract

Objective: To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection.

Methods: Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup.

Results: Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient-years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone.

Conclusion: We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor treatment following a serious infection. The risk of a subsequent serious infection was lower in patients treated with both a TNF inhibitor and a nonbiologic DMARD compared with that in patients treated with a nonbiologic DMARD alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy
  • Arthritis, Psoriatic / epidemiology
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / epidemiology
  • Biological Products / therapeutic use*
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • Infections / epidemiology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / epidemiology
  • Risk
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / epidemiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Adrenal Cortex Hormones
  • Antirheumatic Agents
  • Biological Products
  • Tumor Necrosis Factor-alpha