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).
OBJECTIVE
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.


BACKGROUND
NCT00660647.
Department of Rheumatology, King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark Institute of Health Research, University of Southern Denmark, Gråsten, Denmark.
K
K
Hørslev-Petersen
Department of Rheumatology, Copenhagen University Hospital Glostrup, Glostrup, Denmark Center for Rheumatology and Spine Diseases, Glostrup Hospital, Glostrup, Denmark.
M L
ML
Hetland
Department of Rheumatology, Copenhagen University Hospital Glostrup, Glostrup, Denmark Center for Rheumatology and Spine Diseases, Glostrup Hospital, Glostrup, Denmark.
L M
LM
Ørnbjerg
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
P
P
Junker
Department of Rheumatology, Copenhagen University Hospital at Gentofte, Gentofte, Denmark.
J
J
Pødenphant
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
T
T
Ellingsen
Department of Medicine, Vejle Regional Hospital, Vejle, Denmark.
P
P
Ahlquist
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
H
H
Lindegaard
Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark.
A
A
Linauskas
Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark.
A
A
Schlemmer
Diagnostic Centre, Silkeborg Region Hospital, Silkeborg, Denmark.
M Y
MY
Dam
Department of Rheumatology, Viborg Regional Hospital, Viborg, Denmark.
I
I
Hansen
Department of Rheumatology, Vendsyssel Hospital, Hjørring, Denmark.
T
T
Lottenburger
Aarhus Hospital NBG, Aarhus University Hospital, Aarhus, Denmark.
C G
CG
Ammitzbøll
Aarhus Hospital NBG, Aarhus University Hospital, Aarhus, Denmark.
A
A
Jørgensen
Department of Rheumatology, Copenhagen University Hospital Glostrup, Glostrup, Denmark Center for Rheumatology and Spine Diseases, Glostrup Hospital, Glostrup, Denmark.
S B
SB
Krintel
Department of Rheumatology, King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark Institute of Health Research, University of Southern Denmark, Gråsten, Denmark.
J
J
Raun
Departments of Medicine and Oncology, Copenhagen University Hospital at Herlev, Herlev, Denmark.
J S
JS
Johansen
Department of Rheumatology, Copenhagen University Hospital Glostrup, Glostrup, Denmark Center for Rheumatology and Spine Diseases, Glostrup Hospital, Glostrup, Denmark.
M
M
Østergaard
Aarhus Hospital NBG, Aarhus University Hospital, Aarhus, Denmark.
K
K
Stengaard-Pedersen
D000068879:Adalimumab / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007270:Injections, Intra-Articular; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011859:Radiography / Q000379:methods; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014221:Triamcinolone / Q000008:administration & dosage*
D018501:Antirheumatic Agents; D005938:Glucocorticoids; D014221:Triamcinolone; D000068879:Adalimumab; D008727:Methotrexate
Corticosteroids; DMARDs (biologic); DMARDs (synthetic); Disease Activity; Early Rheumatoid Arthritis