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)

K Hørslev-Petersen; M L Hetland; L M Ørnbjerg; P Junker; Jan Pødenphanth; 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; Mikkel Østergaard; K Stengaard-Pedersen; OPERA Study-Group

doi:10.1136/annrheumdis-2015-208166

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)

K Hørslev-Petersen, M L Hetland, L M Ørnbjerg, P Junker, Jan Pødenphanth, 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, Mikkel Østergaard, K Stengaard-PedersenOPERA Study-Group

Department of Clinical Medicine

27 Citations (Scopus)

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.

Original language	English
Journal	Annals of the Rheumatic Diseases
Volume	75
Issue number	9
Pages (from-to)	1645-1653
Number of pages	9
ISSN	0003-4967
DOIs	https://doi.org/10.1136/annrheumdis-2015-208166
Publication status	Published - 1 Sept 2016

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Hørslev-Petersen, K., Hetland, M. L., Ørnbjerg, L. M., Junker, P., Pødenphanth, J., Ellingsen, T., Ahlquist, P., Lindegaard, H., Linauskas, A., Schlemmer, A., Dam, M. Y., Hansen, I., Lottenburger, T., Ammitzbøll, C. G., Jørgensen, A., Krintel, S. B., Raun, J., Johansen, J. S., Østergaard, M., ... OPERA Study-Group (2016). 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). Annals of the Rheumatic Diseases, 75(9), 1645-1653. https://doi.org/10.1136/annrheumdis-2015-208166

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). / Hørslev-Petersen, K; Hetland, M L; Ørnbjerg, L M et al.
In: Annals of the Rheumatic Diseases, Vol. 75, No. 9, 01.09.2016, p. 1645-1653.

Research output: Contribution to journal › Journal article › Research › peer-review

Hørslev-Petersen, K, Hetland, ML, Ørnbjerg, LM, Junker, P, Pødenphanth, J, Ellingsen, T, Ahlquist, P, Lindegaard, H, Linauskas, A, Schlemmer, A, Dam, MY, Hansen, I, Lottenburger, T, Ammitzbøll, CG, Jørgensen, A, Krintel, SB, Raun, J, Johansen, JS , Østergaard, M, Stengaard-Pedersen, K & OPERA Study-Group 2016, '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)', Annals of the Rheumatic Diseases, vol. 75, no. 9, pp. 1645-1653. https://doi.org/10.1136/annrheumdis-2015-208166

Hørslev-Petersen K, Hetland ML, Ørnbjerg LM, Junker P, Pødenphanth J, Ellingsen T et al. 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). Annals of the Rheumatic Diseases. 2016 Sept 1;75(9):1645-1653. doi: 10.1136/annrheumdis-2015-208166

Hørslev-Petersen, K ; Hetland, M L ; Ørnbjerg, L M et al. / 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). In: Annals of the Rheumatic Diseases. 2016 ; Vol. 75, No. 9. pp. 1645-1653.

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title = "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.",

author = "K H{\o}rslev-Petersen and Hetland, {M L} and {\O}rnbjerg, {L M} and P Junker and Jan P{\o}denphanth and T Ellingsen and P Ahlquist and H Lindegaard and A Linauskas and A Schlemmer and M.Y. Dam and I. Hansen and T Lottenburger and Ammitzb{\o}ll, {C G} and A. J{\o}rgensen and Krintel, {S B} and J Raun and Johansen, {J S} and Mikkel {\O}stergaard and K Stengaard-Pedersen and {OPERA Study-Group}",

note = "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/",

year = "2016",

month = sep,

day = "1",

doi = "10.1136/annrheumdis-2015-208166",

language = "English",

volume = "75",

pages = "1645--1653",

journal = "Annals of the Rheumatic Diseases",

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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 -