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)

TY - JOUR

T1 - Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction

T2 - a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA)

AU - Hørslev-Petersen, K

AU - Hetland, M L

AU - Ørnbjerg, L M

AU - Junker, P

AU - Pødenphanth, Jan

AU - Ellingsen, T

AU - Ahlquist, P

AU - Lindegaard, H

AU - Linauskas, A

AU - Schlemmer, A

AU - Dam, M.Y.

AU - Hansen, I.

AU - Lottenburger, T

AU - Ammitzbøll, C G

AU - Jørgensen, A.

AU - Krintel, S B

AU - Raun, J

AU - Johansen, J S

AU - Østergaard, Mikkel

AU - Stengaard-Pedersen, K

AU - OPERA Study-Group

N1 - 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/

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

U2 - 10.1136/annrheumdis-2015-208166

DO - 10.1136/annrheumdis-2015-208166

M3 - Journal article

C2 - 26489704

SN - 0003-4967

VL - 75

SP - 1645

EP - 1653

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 9

ER -