title: Impact of biologic agents with and without concomitant methotrexate and at reduced doses in older rheumatoid arthritis patients.
abstract: OBJECTIVE
  To examine whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-tumor necrosis factor (anti-TNF) therapies are used at reduced doses in real-world clinical care settings, not just clinical trials.
  
  
  METHODS
  We conducted a retrospective cohort study among rheumatoid arthritis (RA) patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept, and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologic agents using Cox proportional hazards regression, adjusting for demographics and baseline comorbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months.
  
  
  RESULTS
  Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients who initiated biologic monotherapy were 1.4 (95% confidence interval [95% CI] 1.3-1.5) times more likely to discontinue at 1 year compared to those who initiated combination therapy, and 1.8 (95% CI 1.7-2.0) times more likely if starting infliximab monotherapy. Approximately 10-20% of patients who initiated and adhered to etanercept and adalimumab for ≥12 months subsequently received reduced-dose therapy for an 12 additional months and beyond.
  
  
  CONCLUSIONS
  In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients.
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Fenglong
authors.initials: F
authors.lastname: Xie
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delzell
authors.forename: Huifeng
authors.initials: H
authors.lastname: Yun
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.forename: Kevin
authors.initials: K
authors.lastname: Haynes
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.forename: Timothy
authors.initials: T
authors.lastname: Beukelman
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Saag
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
mesh_terms: D000068879:Adalimumab; D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000008:administration & dosage*; D016208:Databases, Factual; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D000069285:Infliximab; D007267:Injections; D053208:Kaplan-Meier Estimate; D008297:Male; D006278:Medicare; D008727:Methotrexate / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012189:Retrospective Studies; D012646:Self Administration; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate