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).

Abstract

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.

• Authors: K Hørslev-Petersen, M L Hetland, L M Ørnbjerg, P Junker, J Pødenphant, T Ellingsen, P Ahlquist, H Lindegaard, A Linauskas, A Schlemmer, M Y Dam, I Hansen, T Lottenburger, C G Ammitzbøll, A Jørgensen, S B Krintel, J Raun, J S Johansen, M Østergaard, K Stengaard-Pedersen, OPERA Study-Group
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 75 Issue 9 Pg. 1645-53 (Sep 2016) ISSN: 1468-2060 [Electronic] England
• PMID: 26489704 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chemical References

• Antirheumatic Agents
• Glucocorticoids
• Triamcinolone
• Adalimumab
• Methotrexate

Topics

• Adalimumab (administration & dosage)
• Adult
• Aged
• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (diagnostic imaging, drug therapy, pathology)
• Disease Progression
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Glucocorticoids (administration & dosage)
• Humans
• Injections, Intra-Articular
• Maintenance Chemotherapy (methods)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Radiography (methods)
• Remission Induction
• Severity of Illness Index
• Treatment Outcome
• Triamcinolone (administration & dosage)