Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial

Annals of the Rheumatic Diseases - Tập 75 Số 6 - Trang 1043-1050 - 2016
James Dale1, A. Stirling2, Ruiqi Zhang3, David Purves4, Jonathan H. Foley5, Martin Sambrook6, Philip G. Conaghan7,8, Désirée van der Heijde9, Alex McConnachie3, Iain B. McInnes10, Duncan Porter2,10
1Department of Rheumatology, Wishaw General Hospital, 50 Netherton Street, Wishaw, North Lanarkshire ML2 0DP, UK
2Department of Rheumatology, Gartnavel General Hospital, Glasgow, UK
3Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
4Department of Management Science, Strathclyde University, Glasgow, UK
5Department of Radiology, Edinburgh Royal Infirmary, Edinburgh, UK
6Department of Radiology, East Sussex Hospitals Trust, Eastbourne, UK
7Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
8NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
9Department of Rheumatology, Leiden University Medical Centre, Leiden, UK
10Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK

Tóm tắt

ObjectiveTo investigate whether an intensive early rheumatoid arthritis (RA) treat-to-target (T2T) strategy could be improved through the use of musculoskeletal ultrasound (MSUS) assessment of disease activity.Methods111 newly diagnosed patients with RA or undifferentiated arthritis (symptom duration <1 year) were randomised to strategies that aimed to attain either DAS28-erythrocyte sedimentation rate (ESR)<3.2 (control) or a total power Doppler joint count≤1 during a combined DAS28-ESR/MSUS assessment (intervention). MSUS examination was indicated if: DAS28-ESR<3.2 or DAS28-ESR≥3.2 with two swollen joints. Step-up disease-modifying antirheumatic drug (DMARD) escalation was standardised: methotrexate monotherapy, triple therapy and then etanercept/triple therapy. American College of Rheumatology (ACR) core-set variables were assessed 3 monthly by a metrologist blinded to group allocation. MRI of dominant hand and wrist, and plain radiographs of hands and feet were undertaken at baseline and 18 months for grading by two readers using the Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis MRI Scoring System (RAMRIS) and van der Heijde/Sharp Score, respectively. The coprimary outcomes were mean change from baseline of DAS44 and RAMRIS erosion score.ResultsGroups were matched for baseline clinical, demographic and radiographic features. The intervention group received more intensive DMARD therapy. Both groups demonstrated significant improvements in DAS44 (mean change: control −2.58, intervention −2.69; 95% CI difference between groups −0.70 to 0.48; p=0.72). There were no significant between-group differences for any ACR core-set variables, except DAS44 remission after 18 months (control 43%, intervention 66%; p=0.03). There was minimal progression of MRI and radiographic erosions and no difference in imaging outcomes or serious adverse event rates.ConclusionsIn early RA, a MSUS-driven T2T strategy led to more intensive treatment, but was not associated with significantly better clinical or imaging outcomes than a DAS28-driven strategy.Trial registration numberNCT00920478.

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Tài liệu tham khảo

Grigor, 2004, Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial, Lancet, 364, 263, 10.1016/S0140-6736(04)16676-2

Verstappen, 2007, Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial), Ann Rheum Dis, 66, 1443, 10.1136/ard.2007.071092

Bakker, 2011, Early clinical response to treatment predicts 5-year outcome in RA patients: follow-up results from the CAMERA study, Ann Rheum Dis, 70, 1099, 10.1136/ard.2010.137943

Möttönen, 1999, Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group, Lancet, 353, 1568, 10.1016/S0140-6736(98)08513-4

Goekoop-Ruiterman, 2007, Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial, Ann Intern Med, 146, 406, 10.7326/0003-4819-146-6-200703200-00005

Schoels, 2010, Evidence for treating rheumatoid arthritis to target: results of a systematic literature search, Ann Rheum Dis, 69, 638, 10.1136/ard.2009.123976

Singh, 2012, 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis, Arthritis Care Res, 64, 625, 10.1002/acr.21641

Smolen, 2014, EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update, Ann Rheum Dis, 73, 492, 10.1136/annrheumdis-2013-204573

Wolfe, 2004, Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize RA patients with fibromyalgia, J Rheumatol, 31, 695

Leeb, 2004, The DAS28 in rheumatoid arthritis and fibromyalgia patients, Rheumatology (Oxford), 43, 1504, 10.1093/rheumatology/keh322

Pollard, 2010, Fibromyalgic rheumatoid arthritis and disease assessment, Rheumatology (Oxford), 49, 924, 10.1093/rheumatology/kep458

Scirè, 2009, Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Doppler signal predicts short-term relapse, Rheumatology (Oxford), 48, 1092, 10.1093/rheumatology/kep171

Peluso, 2011, Clinical and ultrasonographic remission determines different chances of relapse in early and long standing rheumatoid arthritis, Ann Rheum Dis, 70, 172, 10.1136/ard.2010.129924

Saleem, 2012, Can flare be predicted in DMARD treated RA patients in remission, and is it important? A cohort study, Ann Rheum Dis, 71, 1316, 10.1136/annrheumdis-2011-200548

Brown, 2008, An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis, Arthritis Rheum, 58, 2958, 10.1002/art.23945

Dale, 2013, Tightening up? Impact of musculoskeletal ultrasound disease activity assessment on early rheumatoid arthritis patients treated using a treat to target strategy, Arthritis Care Res, 66, 19, 10.1002/acr.22218

Szkudlarek, 2003, Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis, Arthritis Rheum, 48, 955, 10.1002/art.10877

Felson, 1993, The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials, Arthritis Rheum, 36, 729, 10.1002/art.1780360601

Dolan, 1997, Modeling valuations for EuroQol health states, Med Care, 35, 1095, 10.1097/00005650-199711000-00002

Conaghan, 2005, The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the metacarpophalangeal joints, Ann Rheum Dis, 64, i11, 10.1136/ard.2004.031815

Ejbjerg, 2005, The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint, Ann Rheum Dis, 64, i23, 10.1136/ard.2004.031823

van der Heijde, 1989, Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis, Lancet, 1, 1036, 10.1016/S0140-6736(89)92442-2

Bruynesteyn, 2005, Deciding on progression of joint damage in paired films of individual patients: smallest detectable difference or change, Ann Rheum Dis, 64, 179, 10.1136/ard.2003.018457

Haagsma, 1994, Combination of methotrexate and sulphasalazine vs methotrexate alone: a randomized open clinical trial in rheumatoid arthritis patients resistant to sulphasalazine therapy, Rheumatology, 33, 1049, 10.1093/rheumatology/33.11.1049

van der Heijde, 1990, Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score, Ann Rheum Dis, 49, 916, 10.1136/ard.49.11.916

Haavardsholm, 2005, Reliability and sensitivity to change of the OMERACT rheumatoid arthritis magnetic resonance imaging score in a multireader, longitudinal setting., Arthritis Rheum, 52, 3860, 10.1002/art.21493

Felson, 2011, American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials, Arthritis Rheum, 63, 573, 10.1002/art.30129

Wakefield, 2012, After treat-to-target: can a targeted ultrasound initiative improve RA outcomes?, Ann Rheum Dis, 71, 799, 10.1136/annrheumdis-2011-201048

Balsa, 2010, Superiority of SDAI over DAS-28 in assessment of remission in rheumatoid arthritis patients using power Doppler ultrasonography as a gold standard, Rheumatology (Oxford), 49, 683, 10.1093/rheumatology/kep442

Sakellariou, 2013, In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis, Ann Rheum Dis, 245

Aletaha, 2009, Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment, Arthritis Rheum, 60, 1242, 10.1002/art.24433

Lillegraven, 2012, Remission and radiographic outcome in rheumatoid arthritis: application of the 2011 ACR/EULAR remission criteria in an observational cohort, Ann Rheum Dis, 71, 681, 10.1136/ard.2011.154625

Backhaus, 2009, Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project, Arthritis Rheum, 61, 1194, 10.1002/art.24646

Naredo, 2008, Validity, reproducibility, and responsiveness of a twelve-joint simplified power Doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis, Arthritis Rheum, 59, 515, 10.1002/art.23529

Hammer, 2011, Comparisons of 7- to 78-joint ultrasonography scores: all different joint combinations show equal response to adalimumab treatment in patients with rheumatoid arthritis, Arthritis Res Ther, 13, R78, 10.1186/ar3341

Mandl, 2012, Metrologic properties of ultrasound versus clinical evaluation of synovitis in rheumatoid arthritis: results of a multicenter, randomized study, Arthritis Rheum, 64, 1272, 10.1002/art.33491

Dougados, 2010, Evaluation of several ultrasonography scoring systems for synovitis and comparison to clinical examination: results from a prospective multicentre study of rheumatoid arthritis, Ann Rheum Dis, 69, 828, 10.1136/ard.2009.115493

Backhaus, 2013, The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy, Ann Rheum Dis, 10.1136/annrheumdis-2012-201397

Terslev, 2004, Doppler ultrasound findings in healthy wrists and finger joints, Ann Rheum Dis, 63, 644, 10.1136/ard.2003.009548

Ellegaard, 2007, Ultrasound in finger joints: findings in normal subjects and pitfalls in the diagnosis of synovial disease, Ultraschall Med, 28, 40, 10.1055/s-2007-963170

Padovano, 2015, Prevalence of ultrasound synovial inflammatory findings in healthy subjects, Ann Rheum Dis, 10.1136/annrheumdis-2015-208103

Witt, 2013, Relevance of Grade 1 gray-scale ultrasound findings in wrists and small joints to the assessment of subclinical synovitis in rheumatoid arthritis, Arthritis Rheum, 65, 1694, 10.1002/art.37954

Kitchen, 2015, Greyscale and power Doppler ultrasonographic evaluation of normal synovial joints: correlation with pro- and anti-inflammatory cytokines and angiogenic factors, Rheumatology (Oxford), 54, 458, 10.1093/rheumatology/keu354

Moreland, 2012, A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of early aggressive rheumatoid arthritis trial, Arthritis Rheum, 64, 2824, 10.1002/art.34498

O'Dell, 2013, Therapies for active rheumatoid arthritis after methotrexate failure, N Engl J Med, 369, 307, 10.1056/NEJMoa1303006

Saunders, 2008, Triple therapy in early active rheumatoid arthritis: a randomized, single-blind, controlled trial comparing step-up and parallel treatment strategies, Arthritis Rheum, 58, 1310, 10.1002/art.23449

van Vollenhoven, 2012, Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group SWEFOT trial, Lancet, 379, 1712, 10.1016/S0140-6736(12)60027-0

de Jong, 2014, Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial, Ann Rheum Dis, 73, 1331, 10.1136/annrheumdis-2013-204788

Naredo, 2015, Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis, Rheumatology, 54, 1408, 10.1093/rheumatology/kev006

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Annals of the Rheumatic Diseases

Tập 75 Số 6

1043-1050

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