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Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA)
  1. K Hørslev-Petersen1,2,
  2. M L Hetland3,4,
  3. L M Ørnbjerg3,4,
  4. P Junker5,
  5. J Pødenphant6,
  6. T Ellingsen5,
  7. P Ahlquist7,
  8. H Lindegaard5,
  9. A Linauskas8,
  10. A Schlemmer9,
  11. M Y Dam10,
  12. I Hansen11,
  13. T Lottenburger8,
  14. C G Ammitzbøll12,
  15. A Jørgensen12,
  16. S B Krintel3,4,
  17. J Raun1,2,
  18. J S Johansen13,
  19. M Østergaard3,4,
  20. K Stengaard-Pedersen12,
  21. OPERA Study-Group
    1. 1Department of Rheumatology, King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark
    2. 2Institute of Health Research, University of Southern Denmark, Gråsten, Denmark
    3. 3Department of Rheumatology, Copenhagen University Hospital Glostrup, Glostrup, Denmark
    4. 4Center for Rheumatology and Spine Diseases, Glostrup Hospital, Glostrup, Denmark
    5. 5Department of Rheumatology, Odense University Hospital, Odense, Denmark
    6. 6Department of Rheumatology, Copenhagen University Hospital at Gentofte, Gentofte, Denmark
    7. 7Department of Medicine, Vejle Regional Hospital, Vejle, Denmark
    8. 8Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark
    9. 9Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark
    10. 10Diagnostic Centre, Silkeborg Region Hospital, Silkeborg, Denmark
    11. 11Department of Rheumatology, Viborg Regional Hospital, Viborg, Denmark
    12. 12Aarhus Hospital NBG, Aarhus University Hospital, Aarhus, Denmark
    13. 13Departments of Medicine and Oncology, Copenhagen University Hospital at Herlev, Herlev, Denmark
    1. Correspondence to Professor Kim Hørslev-Petersen, Institute of Regional Health Services Research, University of Southern Denmark, South Jutland Hospital, King Christian X Hospital for Rheumatic Diseases, Toldbodgade 3, Gråsten 6300, Denmark;


    Objectives To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647).

    Methods Disease-modifying antirheumatic drug (DMARD)-naive patients with eRA started methotrexate (20 mg/week) and intra-articular triamcinolone (20 mg/ml) for 2 years. In addition, they were randomised to receive placebo adalimumab (DMARD group, n=91) or adalimumab (40 mg/every other week) (DMARD+adalimumab group, n=89) during the first year. Sulfasalazine and hydroxychloroquine were added if disease activity persisted after 3 months. During year 2, synthetic DMARDs continued. Adalimumab was (re)initiated if active disease reoccurred. Clinical response, remission, disability, quality of life and radiographic changes were assessed.

    Results One year after adalimumab withdrawal, treatment profiles and clinical responses did not differ between groups. In the DMARD/DMARD+adalimumab groups, the median 2-year methotrexate dose was 20/20 mg/week (p=0.45), triple DMARD therapy had been initiated in 33/27 patients (p=0.49), adalimumab was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were DAS28CRP<2.6:69%/66%; Clinical Disease Activity Index ≤2.8:55%/57%; Simplified Disease Activity Index <3.3:54%/49%; American College of Rheumatology/European League against Rheumatism (28 joints):44%/45% (p=0.66–1.00). Radiographic progression (Δtotal Sharp score/year) was similar 1.31/0.53 (p=0.12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04).

    Conclusions An aggressive triamcinolone and synthetic DMARD treat-to-target strategy in eRA provided excellent 2-year clinical and radiographic disease control independent of adalimumab induction therapy. ES progression was slightly less during and following adalimumab induction therapy.

    Trial registration number NCT00660647.

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

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