title: Disability outcomes and dose escalation with etanercept, adalimumab, and infliximab in rheumatoid arthritis patients: a US-based retrospective comparative effectiveness study.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a chronic disease that if left untreated may substantially impair physical functioning. Etanercept, infliximab, and adalimumab are tumor necrosis factor (TNF) blockers whose FDA-approved indications in the US include moderate to severe RA. TNF-blocker dose escalation has been well documented in the literature; however, the comparative effectiveness of these agents remains uncertain.
  
  
  OBJECTIVE
  To compare the effectiveness and dose escalation rates of etanercept, adalimumab, and infliximab in US community settings. We hypothesized that etanercept would be equivalent to infliximab and adalimumab in patient-reported disability 9-15 months after therapy initiation, and that fewer etanercept patients would experience dose escalation.
  
  
  METHODS
  This is a retrospective analysis of the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). Adult patients with no biologic use 6 months before TNF-blocker initiation (index) and with Health Assessment Questionnaire Disability Index (HAQ-DI) scores at index and 9-15 months after index were analyzed (218 etanercept, 93 infliximab, and 40 adalimumab).
  
  
  RESULTS
  HAQ-DI change scores at 9-15 months did not differ by treatment (-0.12, -0.10, and -0.08 points for etanercept, infliximab, and adalimumab, respectively; p = 0.52). Dose increases were observed in 1.4% of etanercept, 10.8% of infliximab (p < 0.001), and 12.5% of adalimumab patients (p = 0.004). HAQ-DI change was associated with pre-index HAQ-DI score (p < 0.0001) and disease duration (p = 0.001).
  
  
  CONCLUSIONS
  Fewer etanercept patients escalated dose than infliximab or adalimumab patients, but improvements in functional disability were similar. These differences may have been influenced by package labeling, mode of administration, or other factors. RA treatment with infliximab and adalimumab in community settings, characterized by dose escalation, did not yield greater disability improvements compared to etanercept, which remained at a relatively stable dose. Uncontrolled treatment selection in this observational design may have influenced outcomes, and prior methotrexate treatment may partly explain disability improvements smaller than typically observed in clinical trials.
authors.affiliation: IMS Consulting Group, Alexandria, VA, USA. vschabert@imscg.com
authors.forename: V F
authors.initials: VF
authors.lastname: Schabert
authors.forename: B
authors.initials: B
authors.lastname: Bruce
authors.forename: C F
authors.initials: CF
authors.lastname: Ferrufino
authors.forename: D R
authors.initials: DR
authors.lastname: Globe
authors.forename: D J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: B
authors.initials: B
authors.lastname: Lingala
authors.forename: J F
authors.initials: JF
authors.lastname: Fries
mesh_terms: D000068879:Adalimumab; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002170:Canada; D006233:Persons with Disabilities; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept