The rheumatoid arthritis treat-to-target trial: a cluster randomized trial within the Corrona rheumatology network

BMC Musculoskeletal Disorders

Joel M Kremer⁵  Jenny Devenport¹  Ani John¹  Jeffrey D Greenberg⁴  Allan Gibofsky³  Katherine C Saunders⁷  Christine J Barr⁷  J Timothy Harrington⁶  George W Reed²  Leslie R Harrold² 

[1] Genentech, Inc, South San Francisco, CA, USA;Department of Orthopedics, University of Massachusetts Medical School, Worcester, MA 01655, USA;Hospital for Special Surgery, New York, NY, USA;NYU Hospital for Joint Diseases, New York, NY, USA;Albany Medical College and the Center for Rheumatology, Albany, NY, USA;University of Massachusetts Medical School, Madison, WI, USA;Corrona, LLC, Southborough, MA, USA

关键词: Usual care;    Corrona;    Rheumatoid arthritis;    Treat to target;   

Others  :  1091679
DOI  :  10.1186/1471-2474-15-389

 received in 2013-05-09, accepted in 2014-11-11,  发布年份 2014

【 摘 要 】

Background

The treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis involves using validated metrics to measure disease activity, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. The study described is a newly launched cluster-randomized behavioral intervention to assess the feasibility and effectiveness of the T2T approach in US rheumatology practices. It is designed to identify patient and provider barriers to implementing T2T management. This initial paper focuses on the novel study design and methods created to provide these insights.

Methods/Design

This trial cluster-randomizes rheumatology practices from the existing Corrona network of private and academic sites rather than patients within sites or individual investigators to provide either T2T or usual care (UC) for qualified patients who meet the 2010 revised American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis and have moderate to high disease activity. Specific medication choices are left to the investigator and patient, rather than being specified in the protocol. Enrollment is expected to be completed by the end of 2013, with 30 practices randomized and enrolling a minimum of 530 patients. During the 12-month follow-up, visits are mandated as frequently as monthly in patients with active disease in the T2T group and every 3 months for the UC group. Safety data are collected at each visit. The coprimary endpoints include a comparison of the proportion of patients achieving low disease activity in the T2T and UC groups and assessment of the feasibility of implementing T2T in rheumatology practices, specifically assessment of the rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity in the 2 groups.

Discussion

This cluster-randomized behavioral intervention study will provide valuable insights on the outcomes and feasibility of employing a T2T treatment approach in clinical practice in the United States.

Trial registration

NCT01407419

【 授权许可】

   
2014 Harrold et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH, National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I Arthritis Rheum 2008, 58(1):15-25.
• [2]Sokka T: Work disability in early rheumatoid arthritis. Clin Exp Rheumatol 2003, 21(5 Suppl 31):S71-S74.
• [3]Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT: The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006, 54(1):26-37.
• [4]Smolen JS, Van Der Heijde DM, St Clair EW, Emery P, Bathon JM, Keystone E, Maini RN, Kalden JR, Schiff M, Baker D, Han C, Han J, Bala M, Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) Study Group: Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum 2006, 54(3):702-710.
• [5]van Vollenhoven RF, Ernestam S, Geborek P, Petersson IF, Coster L, Waltbrand E, Zickert A, Theander J, Thorner A, Hellstrom H, Teleman A, Dackhammar C, Akre F, Forslind K, Ljung L, Oding R, Chatzidionysiou A, Wornert M, Bratt J: Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet 2009, 374(9688):459-466.
• [6]Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, Combe B, Cutolo M, de Wit M, Dougados M, Emery P, Gibofsky A, Gomez-Reino JJ, Haraoui B, Kalden J, Keystone EC, Kvien TK, McInnes I, Martin-Mola E, Montecucco C, Schoels M, van der Heijde D, T2T Expert Committee: Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010, 69(4):631-637.
• [7]Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, Kincaid W, Porter D: Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004, 364(9430):263-269.
• [8]Schipper LG, Vermeer M, Kuper HH, Hoekstra MO, Haagsma CJ, Den Broeder AA, van Riel P, Fransen J, van de Laar MA: A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry. Ann Rheum Dis 2012, 71(6):845-850.
• [9]Verstappen SM, Jacobs JW, van der Veen MJ, Heurkens AH, Schenk Y, ter Borg EJ, Blaauw AA, Bijlsma JW, Utrecht Rheumatoid Arthritis Cohort study group: 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 2007, 66(11):1443-1449.
• [10]Curtis JR, Jain A, Askling J, Bridges SL Jr, Carmona L, Dixon W, Finckh A, Hyrich K, Greenberg JD, Kremer J, Listing J, Michaud K, Mikuls T, Shadick N, Solomon DH, Weinblatt ME, Wolfe F, Zink A: A comparison of patient characteristics and outcomes in selected European and U.S. rheumatoid arthritis registries. Semin Arthritis Rheum 2010, 40(1):2-14. e1
• [11]Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O’Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG: 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 (Hoboken) 2012, 64(5):625-639.
• [12]Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, et al.: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014, 73(3):492-509.
• [13]Cornfield J: Randomization by group: a formal analysis. Am J Epidemiol 1978, 108(2):100-102.
• [14]Donner A, Klar N: Design and Analysis of Cluster Randomization Trials in Health Research. First edition. London, England: Arnold; 2000.
• [15]Murray DM, Varnell SP, Blitstein JL: Design and analysis of group-randomized trials: a review of recent methodological developments. Am J Public Health 2004, 94(3):423-432.
• [16]Pappas DA, Kremer JM, Reed G, Greenberg JD, Curtis JR: Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients. BMC Musculoskelet Disord 2014, 15:113-2474-15-113.
• [17]Anderson J, Caplan L, Yazdany J, Robbins ML, Neogi T, Michaud K, Saag KG, O’Dell JR, Kazi S: Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken) 2012, 64(5):640-647.
• [18]Guittet L, Ravaud P, Giraudeau B: Planning a cluster randomized trial with unequal cluster sizes: practical issues involving continuous outcomes. BMC Med Res Methodol 2006, 6:17. BioMed Central Full Text