title: Clinical consequences of delayed addition of adalimumab to methotrexate therapy over 5 years in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  This Year 5 analysis of an open-label extension (OLE) study assessed radiographic progression, clinical efficacy, and safety of adalimumab with concomitant methotrexate (MTX) for patients with active rheumatoid arthritis.
  
  
  METHODS
  In a double-blind study (DE019, NCT00195702), inadequate responders to MTX were randomized to MTX plus either adalimumab 40 mg eow, adalimumab 20 mg weekly, or placebo for 52 weeks. Eligible patients entered an ongoing OLE and received adalimumab 40 mg eow plus MTX. Longterm efficacy and safety were evaluated.
  
  
  RESULTS
  Of 457 patients who had enrolled in the OLE, 304 remained in the study at Year 5, including 112, 107, and 85 from the original adalimumab 40 mg, adalimumab 20 mg, and placebo groups, respectively. Year 5 radiographs demonstrated mean changes in modified total Sharp score for the original adalimumab 40 mg eow and 20 mg weekly groups of 0.8 and 2.6, respectively, versus 3.9 for placebo; 58% from the adalimumab 40 mg eow group had no radiographic progression versus 40% of those who initially received placebo. Of patients who received adalimumab 40 mg eow for 5 years, 26.1% achieved clinical remission (Disease Activity Score 28-joint count < 2.6), had no radio graphic progression (change in modified total Sharp score ≤ 0.5), and had normal function (Health Assessment Questionnaire ≤ 0.5), versus 11.9% of those who initially received placebo. Serious infection rate for 553 patients who received at least one dose of adalimumab was 4.4/100 patient-years.
  
  
  CONCLUSIONS
  A 52-week delay in adding adalimumab to MTX led to worse radiographic, functional, and clinical outcomes at Year 5 for most patients who initially received placebo instead of adalimumab.
authors.affiliation: Division of Advanced Therapeutics, Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, 60 Murray Street, Toronto, Ontario, Canada. edkeystone@mtsinai.on.ca
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Kaushik
authors.initials: K
authors.lastname: Patra
authors.forename: Aileen L
authors.initials: AL
authors.lastname: Pangan
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate