SMART Study: A Study of Re-treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on Anti-TNF Alfa Therapy

Summary

This study will compare the efficacy and safety of re-treatment with 2 doses of MabThera (rituximab) in patients with active rheumatoid arthritis (RA) who have previously experienced an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapies etanercept, infliximab or adalimumab therapy. All patients will receive infusions of 1000 mg intravenous (IV) MabThera on Days 1 and 15; at Week 24 patients who have demonstrated a moderate or good response will be randomized to receive re-treatment with either 1 or 2 additional infusions of 1000 mg IV MabThera. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.

Timeline

Start

2006-09

Primary completion

2011-11

Completion

2011-11

Outcome

Met primary endpoint

paper The adjusted mean difference in DAS28-CRP AUC (PP) was 51.4 (95% CI -131.2 to 234), demonstrating non-inferiority between arms A and B. PMID 23723317 ↗

Publications

• de Jong TD, Sellam J, Agca R, Vosslamber S, Witte BI, Tsang-A-Sjoe M, Mantel E, Bijlsma JW, Voskuyl AE, Nurmohamed MT, Verweij CL, Mariette X. A multi-parameter response prediction model for rituximab in rheumatoid arthritis. Joint Bone Spine. 2018 Mar;85(2):219-226. doi: 10.1016/j.jbspin.2017.02.015. Epub 2017 Mar 28.
• Sellam J, Riviere E, Courties A, Rouzaire PO, Tolusso B, Vital EM, Emery P, Ferraccioli G, Soubrier M, Ly B, Hendel Chavez H, Taoufik Y, Dougados M, Mariette X. Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis. Arthritis Res Ther. 2016 Dec 13;18(1):294. doi: 10.1186/s13075-016-1190-z.
• Sellam J, Rouanet S, Hendel-Chavez H, Miceli-Richard C, Combe B, Sibilia J, Le Loet X, Tebib J, Jourdan R, Dougados M, Taoufik Y, Mariette X. CCL19, a B cell chemokine, is related to the decrease of blood memory B cells and predicts the clinical response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2013 Sep;65(9):2253-61. doi: 10.1002/art.38023.
• Mariette X, Rouanet S, Sibilia J, Combe B, Le Loet X, Tebib J, Jourdan R, Dougados M. Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial. Ann Rheum Dis. 2014 Aug;73(8):1508-14. doi: 10.1136/annrheumdis-2013-203480. Epub 2013 May 30.
• Sellam J, Rouanet S, Hendel-Chavez H, Abbed K, Sibilia J, Tebib J, Le Loet X, Combe B, Dougados M, Mariette X, Taoufik Y. Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2011 Dec;63(12):3692-701. doi: 10.1002/art.30599.
• Sellam J, Hendel-Chavez H, Rouanet S, Abbed K, Combe B, Le Loet X, Tebib J, Sibilia J, Taoufik Y, Dougados M, Mariette X. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011 Apr;63(4):933-8. doi: 10.1002/art.30233.

Drugs

Indications