Differences in annual medication costs and rates of dosage increase between tumor necrosis factor-antagonist therapies for rheumatoid arthritis in a managed care population

Clin Ther. 2009 Apr;31(4):825-35. doi: 10.1016/j.clinthera.2009.04.002.


Background: Tumor necrosis factor (TNF) antagonists are commonly used to treat rheumatoid arthritis (RA). Differences in the dosage and mode of administration of these agents may result in differential rates of dosage adjustment and costs of care.

Objective: This study compared dosing patterns and annual costs associated with the use of the subcutaneous TNF antagonists adalimumab and etanercept, and the intravenous TNF antagonist infliximab.

Methods: A large managed care database (PharMetrics) was used to identify patients with RA who newly initiated TNF-antagonist therapy with adalimumab, etanercept, or infliximab on or after January 1, 2003, and had at least 6 months of continuous health plan enrollment before initiation of therapy and 12 months of continuous enrollment after initiation. The patients were followed over 12 months of enrollment. Annual pharmacy, inpatient, and outpatient costs were estimated based on plan reimbursements and were compared between cohorts. The average daily dosage (ADD) between prescription refills was used to compare the percentages of patients with greater-than-expected dosing (GTED), defined as 2 consecutive increases in ADD relative to the patient's established maintenance dosage.

Results: A total of 2382 patients (568 adalimumab, 1181 etanercept, 633 infliximab) were included in the analysis. Significantly more patients had GTED with infliximab compared with adalimumab and etanercept (32.1%, 8.5%, and 4.7%, respectively; both comparisons, P < 0.05). For patients with a dosage increase, the mean time to the first GTED was significantly shorter for infliximab compared with adalimu-mab and etanercept (154.5, 173.3, and 167.9 days; both, P < 0.05). The mean annual costs of anti-TNF therapy, adjusted for baseline differences, were significantly greater for infliximab compared with adalimumab and etanercept ($15,617, $12,200, and $12,146; both, P < 0.05). There were also significant differences between infliximab relative to adalimumab and etanercept in total RA-related medication costs ($16,280, $12,989, and $12,794; P < 0.05) and total pharmacy costs ($17,854, $14,805, and $14,398; P < 0.05).

Conclusion: Patients initiating TNF-antagonist treatment for RA with infliximab incurred annual medication costs that were nearly 30% greater than costs in those initiating therapy with adalimumab or etanercept, in part because of the significantly greater rate of GTED in infliximab recipients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / economics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / economics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / economics
  • Cohort Studies
  • Databases, Factual
  • Dose-Response Relationship, Drug
  • Drug Costs
  • Etanercept
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / economics
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Longitudinal Studies
  • Male
  • Managed Care Programs / economics
  • Middle Aged
  • Pharmaceutical Services / economics
  • Receptors, Tumor Necrosis Factor / administration & dosage
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


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