title: Tumor necrosis factor blocker dose escalation among biologic naïve rheumatoid arthritis patients in commercial managed-care plans in the 2 years following therapy initiation.
abstract: OBJECTIVE
  This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab.
  
  
  METHODS
  Non-elderly adult (age 18-65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose.
  
  
  RESULTS
  A total of 2747 patients met the inclusion criteria (mean age 50 years [SD=10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8-1.5% for etanercept, 10.8-12.5% for adalimumab, and 16.4-42.5% for infliximab; ranges at 24 months were 0.8-2.1% for etanercept, 14.3-17.5% for adalimumab, and 26.4-57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p<0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions.
  
  
  CONCLUSIONS
  Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.
authors.affiliation: machaon.bonafede@thomsonreuters.com
authors.forename: Machaon M K
authors.initials: MM
authors.lastname: Bonafede
authors.forename: Shravanthi R
authors.initials: SR
authors.lastname: Gandra
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Fox
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Wilson
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D000069285:Infliximab; D007345:Insurance Claim Review; D008297:Male; D008329:Managed Care Programs; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept