title: Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial.
abstract: OBJECTIVE
  An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRP<3.2) at 12 months.
  
  
  METHODS
  In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (<6 months duration) received methotrexate 7.5 mg/week (increased to 20 mg/week within 2 months) plus adalimumab 40 mg every other week (adalimumab-group, n=89) or methotrexate+placebo-adalimumab (placebo-group, n=91). At all visits, triamcinolone was injected into swollen joints (max. four joints/visit). If low disease activity was not achieved, sulfasalazine 2 g/day and hydroxychloroquine 200 mg/day were added after 3 months, and open-label biologics after 6-9 months. Efficacy was assessed primarily on the proportion of patients who reached treatment target (DAS28CRP<3.2). Secondary endpoints included DAS28CRP, remission, Health Assessment Questionnaire (HAQ), EQ-5D and SF-12. Analysis was by intention-to-treat with last observation carried forward.
  
  
  RESULTS
  Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRP<3.2 was reached in 80%/76% (p=0.65) and DAS28CRP was 2.0 (1.7-5.2) (medians (5th/95th percentile ranges)), versus 2.6 (1.7-4.7) (p=0.009). Remission rates were: DAS28CRP<2.6: 74%/49%, Clinical Disease Activity Index≤2.8: 61%/41%, Simplified Disease Activity Index<3.3: 57%/37%, European League Against Rheumatism/American College of Rheumatology Boolean: 48%/30% (0.0008<p<0.014, number-needed-to-treat: 4.0-5.4). Twelve months HAQ, SF12PCS and EQ-5D improvements were most pronounced in the adalimumab group. Treatments were well tolerated.
  
  
  CONCLUSIONS
  Adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment did not increase the proportion of patients who reached the DAS28CRP<3.2 treatment target, but improved DAS28CRP, remission rates, function and quality of life in DMARD-naïve ERA.
authors: Department of Rheumatology, King Christian 10th Hospital for Rheumatic Diseases, , Gråsten, Denmark; South Jutland Hospital, Institute of Regional Health Services Research, University of Southern Denmark, , Odense, Denmark.
authors: Kim
authors: K
authors: Hørslev-Petersen
authors: Merete Lund
authors: ML
authors: Hetland
authors: Peter
authors: P
authors: Junker
authors: Jan
authors: J
authors: Pødenphant
authors: Torkell
authors: T
authors: Ellingsen
authors: Palle
authors: P
authors: Ahlquist
authors: Hanne
authors: H
authors: Lindegaard
authors: Asta
authors: A
authors: Linauskas
authors: Annette
authors: A
authors: Schlemmer
authors: Mette Yde
authors: MY
authors: Dam
authors: Ib
authors: I
authors: Hansen
authors: Hans Christian
authors: HC
authors: Horn
authors: Christian Gytz
authors: CG
authors: Ammitzbøll
authors: Anette
authors: A
authors: Jørgensen
authors: Sophine B
authors: SB
authors: Krintel
authors: Johnny
authors: J
authors: Raun
authors: Julia S
authors: JS
authors: Johansen
authors: Mikkel
authors: M
authors: Østergaard
authors: Kristian
authors: K
authors: Stengaard-Pedersen
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014221:Triamcinolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014221:Triamcinolone; D000068879:Adalimumab; D008727:Methotrexate
keywords: Corticosteroids; DMARDs (biologic); DMARDs (synthetic); Disease Activity; Early Rheumatoid Arthritis