title: Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial.
abstract: BACKGROUND
  Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be sustained with reduced doses or withdrawal of etanercept in patients with moderately active disease.
  
  
  METHODS
  In a randomised controlled trial, patients aged between 18 and 70 years with moderately active rheumatoid arthritis (disease activity score in 28 joints [DAS28] >3.2 and ≤5.1) despite treatment with methotrexate were enrolled at 80 centres in Europe, Latin America, Asia, and Australia between March 6, 2008, and Sept 9, 2009. To be eligible, patients had to have been receiving 15-25 mg of methotrexate every week for at least 8 weeks. In an open-label period of 36 weeks, all patients were given 50 mg etanercept plus methotrexate every week. To be eligible for a subsequent double-blind period of 52 weeks, participants had to have achieved sustained low disease activity. These patients were randomly assigned (1:1:1) by an interactive voice-response system to one of three treatment groups: 50 mg etanercept plus methotrexate, 25 mg etanercept plus methotrexate, or placebo plus methotrexate. Patients were stratified in blocks of three by DAS28 response (low disease activity or remission) at week 36. Patients, investigators, data analysts, and study staff were all masked to treatment allocation. The primary endpoint was the proportion of patients with low disease activity at week 88 in the groups given 50 mg etanercept or placebo in the double-blind period. A conditional primary endpoint was the proportion of patients receiving 25 mg etanercept who achieved low disease activity. Modified intention-to-treat populations were used for analyses. This trial is registered with ClinicalTrials.gov, number NCT00565409.
  
  
  RESULTS
  604 (72.4%) of 834 enrolled patients were eligible for the double-blind period, of whom 202 were assigned to 50 mg etanercept plus methotrexate, 202 to 25 mg etanercept plus methotrexate, and 200 to placebo plus methotrexate. At week 88, 166 (82.6%) of 201 patients who had received at least one dose of 50 mg etanercept and one or more DAS28 evaluations had low disease activity, compared with 84 (42.6%) of 197 who had received placebo (mean difference 40.8%, 95% CI 32.5-49.1%; p<0.0001). Additionally, 159 (79.1%) of 201 patients given 25 mg etanercept had low disease activity at week 88 (mean difference from placebo 35.9%, 27.0-44.8%; p<0.0001).
  
  
  CONCLUSIONS
  Conventional or reduced doses of etanercept with methotrexate in patients with moderately active rheumatoid arthritis more effectively maintain low disease activity than does methotrexate alone after withdrawal of etanercept.
  
  
  BACKGROUND
  Pfizer.
authors: Division of Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria. josef.smolen@wienkav.at
authors: Josef S
authors: JS
authors: Smolen
authors: Peter
authors: P
authors: Nash
authors: Patrick
authors: P
authors: Durez
authors: Stephen
authors: S
authors: Hall
authors: Elena
authors: E
authors: Ilivanova
authors: Fedra
authors: F
authors: Irazoque-Palazuelos
authors: Pedro
authors: P
authors: Miranda
authors: Min-Chan
authors: MC
authors: Park
authors: Karel
authors: K
authors: Pavelka
authors: Ronald
authors: R
authors: Pedersen
authors: Annette
authors: A
authors: Szumski
authors: Constance
authors: C
authors: Hammond
authors: Andrew S
authors: AS
authors: Koenig
authors: Bonnie
authors: B
authors: Vlahos
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018771:Arthralgia / Q000209:etiology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept; D008727:Methotrexate