Comparison of methods for measuring dose escalation of the subcutaneous TNF antagonists for rheumatoid arthritis patients treated in routine clinical practice

Curr Med Res Opin. 2010 Jul;26(7):1637-45. doi: 10.1185/03007995.2010.483127.


Objectives: Tumor necrosis factor (TNF) antagonists, most frequently prescribed biologics for moderate to severe rheumatoid arthritis (RA), are subject to dose escalation. Even though different methods have been employed to estimate the timing and magnitude of dose escalation, there is no consensus on which method is optimal. The purpose was to evaluate different methods for assessing dose escalation patterns for the subcutaneously delivered TNF antagonists, etanercept and adalimumab.

Methods: Five different methods to describe dose escalation patterns were compared using a large administrative claims database from US health plans. RA patients age 18 and above with >or=2 claims for etanercept or adalimumab were included. These methods included last dose versus index dose (the dose of a patient's first biologic prescription [adalimumab or etanercept]), average dose versus recommended dose, multiple (>or=2) instances of subsequent doses exceeding the index dose, subsequent doses exceeding a predetermined threshold above the index dose, and the time-trend method, comparing each subsequent dose throughout the course of therapy to the index dose.

Results: A total of 1369 etanercept and 461 adalimumab RA patients were evaluated for dose escalation. Estimates of dose escalation were highest for both drugs based on the average dose method (10.3% for etanercept, 33.6% for adalimumab). The time-trend method demonstrated the temporal trends in the percent of patients with dose escalation. Adalimumab patients had a higher rate of dose escalation than etanercept patients, regardless of method. The study is limited in that it could not assess the reason for or clinical outcomes associated with dose escalation.

Conclusions: Different methods for evaluating dose escalation yield different numerical estimates but consistently give the same overall comparative result. The choice of method should depend on the specific research question. The average dose method may be the most useful for cost impact studies, whereas the time-trend method provides the most comprehensive information on dose patterns.

Publication types

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

MeSH terms

  • Adalimumab
  • Adult
  • Algorithms
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / administration & dosage*
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations*
  • Etanercept
  • Female
  • Hormone Antagonists / administration & dosage
  • Humans
  • Immunoglobulin G / administration & dosage
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Professional Practice* / statistics & numerical data
  • Receptors, Tumor Necrosis Factor / administration & dosage
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


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