title: Medication effectiveness with the use of tumor necrosis factor inhibitors among Texas Medicaid patients diagnosed with rheumatoid arthritis.
abstract: BACKGROUND
  Adalimumab (Humira [ADA]), etanercept (Enbrel [ETN]), and infliximab (Remicade [IFX]) are tumor necrosis factor (TNF) inhibitors indicated for the treatment of a variety of disorders. While their effectiveness has not been directly compared in a clinical trial, results from the majority of the indirect treatment comparisons suggest comparable efficacy and safety profiles. However, these TNF inhibitor agents differ in administration method and dosing flexibility, which may result in differences in medication use profiles (e.g., adherence, persistence, discontinuation, dose escalation, and switching to a new biologic rheumatoid arthritis drug) and effectiveness in clinical practice.
  
  
  OBJECTIVE
  To estimate the effectiveness of ADA, ETN, and IFX in patients with rheumatoid arthritis (RA) using a validated, claims-based algorithm designed for large retrospective databases.
  
  
  METHODS
  Adult (aged 18-63 years) patients diagnosed with RA, and receiving ADA, ETN, or IFX, and insured by Texas Medicaid were included. The index date was the date of the first prescription claim for ADA or ETN or infusion record for IFX with no claim or infusion record of a biologic drug in the preceding 6 months (i.e., biologic naïve). The study time frame was from July 2003 to August 2011, and prescription and medical claims for each subject were analyzed over an 18-month period (6 months pre- and 12 months post-index). Based on a RA medication effectiveness algorithm (Curtis et al. 2011), a RA medication was classified as effective if each of the following 6 criteria were met: (1) high medication adherence (i.e., medication possession ratio [MPR] ≥ 80%, defined as the sum of days' supply for all fills or infusions divided by the number of days in the study period); (2) no switching to (or addition of) new biologic RA drugs; (3) no addition of new nonbiologic RA drugs; (4) no increase in dose or frequency of administration of the RA medication currently evaluated; (5) no more than 1 glucocorticoid (GC) joint injection; and (6) no increase in dose of a concurrent oral GC. Propensity score (PS) matching was employed, and paired tests (i.e., McNemar's) and multivariate conditional logistic regression analysis were used to compare groups. Demographic (i.e., age, gender, race) and clinical (i.e., use of nonbiologic disease-modifying antirheumatic drugs [DMARDs], pain medication use, GC medication use, RA-related and non-RA-related health care visits [i.e., ambulatory and inpatient visits], number of nonstudy RA medications, and comorbidity index) characteristics, including total health care utilization cost at baseline, served as study covariates.
  
  
  RESULTS
  After PS matching, 822 patients (n = 274 per group) were included. The majority of the sample (69.2%) was between 45-63 years, female (88%), and Hispanic (53.7%). Results for each TNF inhibitor differed significantly for 2 of the 6 effectiveness criteria (i.e., medication adherence and dose escalation). A significantly higher proportion of patients on IFX were adherent compared with patients on ETN or ADA (38.3% vs. 16.4% and 21.2%, P  less than  0.0001 for both). Adherence rates between ETN and ADA were not significantly different. A significantly higher (P  less than  0.0001) proportion of patients on ETN had no dose escalation compared with patients on ADA or IFX (98.2% vs. 88.7% and 80.3%, P  less than  0.0001). Dose escalation rate was also significantly lower (P = 0.0106) for ADA compared with IFX. The multivariate conditional logistic regression analysis indicated no significant difference in overall effectiveness using the claims-based algorithm among the 3 TNF inhibitors nor any significant relationship between effectiveness and the study covariates.
  
  
  CONCLUSIONS
  The study results suggest that when using a medication effectiveness algorithm, IFX, ETN, and ADA have comparable effectiveness in patients with RA. Patient adherence to therapy may be higher if given IFX, and patients who receive ETN are less likely to have a dose escalation.
authors: The University of Texas at Austin, 2409 University Ave., STOP A1930, Austin, TX 78712-1120. jbarner@austin.utexas.edu.
authors: Abiola
authors: A
authors: Oladapo
authors: Jamie C
authors: JC
authors: Barner
authors: Kenneth A
authors: KA
authors: Lawson
authors: Suzanne
authors: S
authors: Novak
authors: Karen L
authors: KL
authors: Rascati
authors: Kristin M
authors: KM
authors: Richards
authors: David J
authors: DJ
authors: Harrison
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008484:Medicaid; D055118:Medication Adherence; D008875:Middle Aged; D015999:Multivariate Analysis; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D013781:Texas; D016896:Treatment Outcome; 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