Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare

Arthritis Rheumatol. 2016 Jan;68(1):56-66. doi: 10.1002/art.39399.

Abstract

Objective: The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA.

Methods: In a retrospective cohort study using Medicare data from 2006-2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of >30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders.

Results: Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person-years (abatacept) to 18.7 per 100 person-years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07-1.45), infliximab (HR 1.39, 95% CI 1.21-1.60), and rituximab (HR 1.36, 95% CI 1.21-1.53) had significantly higher HRs for hospitalized infection compared with abatacept.

Conclusion: In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1-year risk of hospitalized infection compared with the risk associated with exposure to abatacept.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept / therapeutic use
  • Adalimumab / therapeutic use
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Biological Products / therapeutic use*
  • Certolizumab Pegol / therapeutic use
  • Cohort Studies
  • Etanercept / therapeutic use
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Infections / epidemiology
  • Infliximab / therapeutic use
  • Length of Stay / statistics & numerical data
  • Male
  • Medicare
  • Middle Aged
  • Pneumonia / epidemiology*
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Rituximab / therapeutic use
  • Sepsis / epidemiology*
  • Soft Tissue Infections / epidemiology*
  • United States / epidemiology
  • Urinary Tract Infections / epidemiology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biological Products
  • Rituximab
  • Abatacept
  • golimumab
  • Infliximab
  • Adalimumab
  • tocilizumab
  • Etanercept
  • Certolizumab Pegol