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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
  1. Kim Hørslev-Petersen1,
  2. Merete Lund Hetland2,
  3. Peter Junker3,
  4. Jan Pødenphant4,
  5. Torkell Ellingsen5,
  6. Palle Ahlquist6,
  7. Hanne Lindegaard3,
  8. Asta Linauskas7,
  9. Annette Schlemmer8,
  10. Mette Yde Dam5,
  11. Ib Hansen9,
  12. Hans Christian Horn6,
  13. Christian Gytz Ammitzbøll10,
  14. Anette Jørgensen10,
  15. Sophine B Krintel2,
  16. Johnny Raun1,
  17. Julia S Johansen11,
  18. Mikkel Østergaard2,
  19. Kristian Stengaard-Pedersen10,
  20. OPERA study-group
  1. 1Department 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
  2. 2Department of Rheumatology and DANBIO, Glostrup Hospital; Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
  3. 3Department of Rheumatology C, Odense University Hospital, University of Southern Denmark, Denmark
  4. 4Department of Rheumatology, Gentofte Hospital; Faculty of Health Sciences, University of Copenhagen, Odense, Denmark
  5. 5Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark
  6. 6Department of Medicine, Vejle Regional Hospital, Vejle, Denmark
  7. 7Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark
  8. 8Department of Rheumatology, Aarhus University Hospital, Aalborg, Denmark; Aalborg Hospital, Aalborg, Denmark
  9. 9Department of Rheumatology, Viborg Regional Hospital, Viborg, Denmark
  10. 10Department of Rheumatology, Aarhus University Hospital; Aarhus Hospital NBG, Aarhus, Denmark
  11. 11Department of Medicine and Oncology, Herlev Hospital; Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Professor Kim Hørslev-Petersen, Institute of Regional Health Services Research, University of Southern Denmark, South Jutland Hospital, King Christian 10th Hospital for Rheumatic Diseases, Toldbodgade 3, Gråsten 6300, Denmark; khorslevpetersen{at}gigtforeningen.dk

Abstract

Objectives 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.

  • Early Rheumatoid Arthritis
  • Disease Activity
  • DMARDs (biologic)
  • DMARDs (synthetic)
  • Corticosteroids

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