FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 353:1114-1123 September 15, 2005 Number 11 Next

Abatacept for Rheumatoid Arthritis Refractory to Tumor Necrosis Factor Inhibition

	Full Text PDF PDA Full Text PowerPoint Slide Set Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article

ABSTRACT

Background A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor (TNF-) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti–TNF- therapy.

Methods Patients with active rheumatoid arthritis and an inadequate response to anti–TNF- therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug. Patients discontinued anti–TNF- therapy before randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed.

Results After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001; and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group.

Conclusions Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti–TNF- therapy.

Source Information

From Stanford University Medical Center, Stanford, Calif. (M.C.G.); Bristol-Myers Squibb, Princeton, N.J. (J.-C.B., K.N., I.N., T.L., R.A., D.T.H.); the Denver Arthritis Clinic, Denver (M.S.); the University of Cincinnati Medical Center, Cincinnati (M.L.); the Center for Rheumatology, Immunology and Arthritis, Fort Lauderdale, Fla. (Y.S.); the Center for Rheumatology and Albany Medical College, Albany, N.Y. (J.K.); the University of Massachusetts Medical School, Worcester (C.B.); Carolina Bone and Joint, Charlotte, N.C. (J.B.); and Rene Descartes University, Service de Rhumatologie B, Paris (M.D.).

Address reprint requests to Dr. Genovese at the Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford University Medical Center, 1000 Welch Rd., Suite 203, Palo Alto, CA 94304, or at genovese{at}stanford.edu.

Full Text of this Article

This article has been cited by other articles:

• Simon, T A, Smitten, A L, Franklin, J, Askling, J, Lacaille, D, Wolfe, F, Hochberg, M C, Qi, K, Suissa, S (2009). Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment. Ann Rheum Dis 68: 1819-1826 [Abstract] [Full Text]  
• Westhovens, R, Robles, M, Ximenes, A C, Nayiager, S, Wollenhaupt, J, Durez, P, Gomez-Reino, J, Grassi, W, Haraoui, B, Shergy, W, Park, S-H, Genant, H, Peterfy, C, Becker, J-C, Covucci, A, Helfrick, R, Bathon, J (2009). Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis 68: 1870-1877 [Abstract] [Full Text]  
• Schiff, M, Pritchard, C, Huffstutter, J E, Rodriguez-Valverde, V, Durez, P, Zhou, X, Li, T, Bahrt, K, Kelly, S, Le Bars, M, Genovese, M C (2009). The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis 68: 1708-1714 [Abstract] [Full Text]  
• KOUMAKIS, E., WIPFF, J., AVOUAC, J., KAHAN, A., ALLANORE, Y. (2009). Severe Refractory Rheumatoid Arthritis Successfully Treated with Combination Rituximab and Anti-Tumor Necrosis Factor-{alpha}-Blocking Agents. The Journal of Rheumatology 36: 2125-2126 [Full Text]  
• Pavelka, K, Jarosova, K, Suchy, D, Senolt, L, Chroust, K, Dusek, L, Vencovsky, J (2009). Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy. Ann Rheum Dis 68: 1285-1289 [Abstract] [Full Text]  
• Dodson, L. F., Boomer, J. S., Deppong, C. M., Shah, D. D., Sim, J., Bricker, T. L., Russell, J. H., Green, J. M. (2009). Targeted Knock-In Mice Expressing Mutations of CD28 Reveal an Essential Pathway for Costimulation. Mol. Cell. Biol. 29: 3710-3721 [Abstract] [Full Text]  
• Buch, M H, Boyle, D L, Rosengren, S, Saleem, B, Reece, R J, Rhodes, L A, Radjenovic, A, English, A, Tang, H, Vratsanos, G, O'Connor, P, Firestein, G S, Emery, P (2009). Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study. Ann Rheum Dis 68: 1220-1227 [Abstract] [Full Text]  
• HARAOUI, B. (2009). Assessment and Management of Rheumatoid Arthritis. The Journal of Rheumatology Supplement 82: 2-10 [Abstract] [Full Text]  
• RUSSELL, A. S. (2009). Relative Efficacies: Antimalarials to Abatacept - The Choice Is Ours. The Journal of Rheumatology Supplement 82: 17-24 [Abstract] [Full Text]  
• KHRAISHI, M. (2009). Comparative Overview of Safety of the Biologics in Rheumatoid Arthritis. The Journal of Rheumatology Supplement 82: 25-32 [Abstract] [Full Text]  
• WELLS, G. A. (2009). Patient-Driven Outcomes in Rheumatoid Arthritis. The Journal of Rheumatology Supplement 82: 33-38 [Abstract] [Full Text]  
• Wells, G, Becker, J-C, Teng, J, Dougados, M, Schiff, M, Smolen, J, Aletaha, D, van Riel, P L C M (2009). Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis 68: 954-960 [Abstract] [Full Text]  
• WESTHOVENS, R., KREMER, J. M., MORELAND, L. W., EMERY, P., RUSSELL, A. S., LI, T., ARANDA, R., BECKER, J.-C., QI, K., DOUGADOS, M. (2009). Safety and Efficacy of the Selective Costimulation Modulator Abatacept in Patients with Rheumatoid Arthritis Receiving Background Methotrexate: A 5-year Extended Phase IIB Study. The Journal of Rheumatology 36: 736-742 [Abstract] [Full Text]  
• Goldring, S. R (2009). Periarticular bone changes in rheumatoid arthritis: pathophysiological implications and clinical utility. Ann Rheum Dis 68: 297-299 [Full Text]  
• Bruce, S. P. (2009). Recent Developments in the Treatment of Rheumatoid Arthritis. Journal of Pharmacy Practice 22: 65-74 [Abstract]  
• WELLS, G. A., BOERS, M., LI, T., TUGWELL, P. S. (2009). Investigating the Validity of the Minimal Disease Activity State for Patients with Rheumatoid Arthritis Treated with Abatacept. The Journal of Rheumatology 36: 260-265 [Abstract] [Full Text]  
• Keystone, E, Emery, P, Peterfy, C G, Tak, P P, Cohen, S, Genovese, M C, Dougados, M, Burmester, G R, Greenwald, M, Kvien, T K, Williams, S, Hagerty, D, Cravets, M W, Shaw, T (2009). Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis 68: 216-221 [Abstract] [Full Text]  
• Li, T., Wells, G., Westhovens, R., Tugwell, P. (2009). Validation of a simple activity participation measure for rheumatoid arthritis clinical trials. Rheumatology (Oxford) 48: 170-175 [Abstract] [Full Text]  
• Salliot, C, Dougados, M, Gossec, L (2009). Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis 68: 25-32 [Abstract] [Full Text]  
• Furst, D E, Keystone, E C, Kirkham, B, Fleischmann, R, Mease, P, Breedveld, F C, Smolen, J S, Kalden, J R, Burmester, G R, Braun, J, Emery, P, Winthrop, K, Bresnihan, B, De Benedetti, F, Dorner, T, Gibofsky, A, Schiff, M H, Sieper, J, Singer, N, Van Riel, P L C M, Weinblatt, M E, Weisman, M H (2008). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2008. Ann Rheum Dis 67: iii2-iii25 [Full Text]  
• Smolen, J. S, Weinblatt, M. E (2008). When patients with rheumatoid arthritis fail tumour necrosis factor inhibitors: what is the next step?. Ann Rheum Dis 67: 1497-1498 [Full Text]  
• Hegen, M, Keith, J C Jr, Collins, M, Nickerson-Nutter, C L (2008). Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann Rheum Dis 67: 1505-1515 [Abstract] [Full Text]  
• Axmann, R, Herman, S, Zaiss, M, Franz, S, Polzer, K, Zwerina, J, Herrmann, M, Smolen, J, Schett, G (2008). CTLA-4 directly inhibits osteoclast formation. Ann Rheum Dis 67: 1603-1609 [Abstract] [Full Text]  
• Kavanaugh, A, Klareskog, L, van der Heijde, D, Li, J, Freundlich, B, Hooper, M (2008). Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate. Ann Rheum Dis 67: 1444-1447 [Abstract] [Full Text]  
• Isaacs, J. D. (2008). Therapeutic T-cell manipulation in rheumatoid arthritis: past, present and future. Rheumatology (Oxford) 47: 1461-1468 [Abstract] [Full Text]  
• (2008). Rituximab and {blacktriangledown}abatacept for rheumatoid arthritis. DTB 46: 57-61 [Abstract] [Full Text]  
• Schiff, M, Keiserman, M, Codding, C, Songcharoen, S, Berman, A, Nayiager, S, Saldate, C, Li, T, Aranda, R, Becker, J-C, Lin, C, Cornet, P L N, Dougados, M (2008). Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis 67: 1096-1103 [Abstract] [Full Text]  
• Genant, H K, Peterfy, C G, Westhovens, R, Becker, J-C, Aranda, R, Vratsanos, G, Teng, J, Kremer, J M (2008). Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis 67: 1084-1089 [Abstract] [Full Text]  
• Cole, J. C., Li, T., Lin, P., MacLean, R., Wallenstein, G. V. (2008). Treatment impact on estimated medical expenditure and job loss likelihood in rheumatoid arthritis: re-examining quality of life outcomes from a randomized placebo-controlled clinical trial with abatacept. Rheumatology (Oxford) 47: 1044-1050 [Abstract] [Full Text]  
• Haupl, T., Ostensen, M., Grutzkau, A., Burmester, G.-R., Villiger, P. M. (2008). Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures. Rheumatology (Oxford) 47: iii19-iii22 [Abstract] [Full Text]  
• Genovese, M C, Schiff, M, Luggen, M, Becker, J-C, Aranda, R, Teng, J, Li, T, Schmidely, N, Le Bars, M, Dougados, M (2008). Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis 67: 547-554 [Abstract] [Full Text]  
• Pincus, T., Bergman, M. J., Yazici, Y., Hines, P., Raghupathi, K., Maclean, R. (2008). An index of only patient-reported outcome measures, routine assessment of patient index data 3 (RAPID3), in two abatacept clinical trials: similar results to disease activity score (DAS28) and other RAPID indices that include physician-reported measures. Rheumatology (Oxford) 47: 345-349 [Abstract] [Full Text]  
• Nolan, A., Weiden, M., Kelly, A., Hoshino, Y., Hoshino, S., Mehta, N., Gold, J. A. (2008). CD40 and CD80/86 Act Synergistically to Regulate Inflammation and Mortality in Polymicrobial Sepsis. Am. J. Respir. Crit. Care Med. 177: 301-308 [Abstract] [Full Text]  
• Aletaha, D, Strand, V, Smolen, J S, Ward, M M (2008). Treatment-related improvement in physical function varies with duration of rheumatoid arthritis: a pooled analysis of clinical trial results. Ann Rheum Dis 67: 238-243 [Abstract] [Full Text]  
• Wells, G, Li, T, Maxwell, L, Maclean, R, Tugwell, P (2008). Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis. Ann Rheum Dis 67: 260-265 [Abstract] [Full Text]  
• Roy, A., Mould, D. R., Wang, X.-F., Tay, L., Raymond, R., Pfister, M. (2007). Modeling and Simulation of Abatacept Exposure and Interleukin-6 Response in Support of Recommended Doses for Rheumatoid Arthritis. J Clin Pharmacol 47: 1408-1420 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Sieper, J, Emery, P, Keystone, E C, Schiff, M H, Mease, P, van Riel, P L C M, Fleischmann, R, Weisman, M H, Weinblatt, M E (2007). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis 66: iii2-iii22 [Full Text]  
• Brown, K. K. (2007). Roger S. Mitchell Lecture. Rheumatoid Lung Disease. Proc Am Thorac Soc 4: 443-448 [Abstract] [Full Text]  
• Bosch, X., Guilabert, A., Espinosa, G., Mirapeix, E. (2007). Treatment of Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Systematic Review. JAMA 298: 655-669 [Abstract] [Full Text]  
• Bruce, S. P, Boyce, E. G (2007). Update on Abatacept: A Selective Costimulation Modulator for Rheumatoid Arthritis. The Annals of Pharmacotherapy 41: 1153-1162 [Abstract] [Full Text]  
• Brenner, M., Laragione, T., Mello, A., Gulko, P. S (2007). Cia25 on rat chromosome 12 regulates severity of autoimmune arthritis induced with pristane and with collagen. Ann Rheum Dis 66: 952-957 [Abstract] [Full Text]  
• Bombardieri, S., Ruiz, A. A., Fardellone, P., Geusens, P., McKenna, F., Unnebrink, K., Oezer, U., Kary, S., Kupper, H., Burmester, G. R., on behalf of the Research in Active Rheumatoid Art, (2007). Effectiveness of adalimumab for rheumatoid arthritis in patients with a history of TNF-antagonist therapy in clinical practice. Rheumatology (Oxford) 46: 1191-1199 [Abstract] [Full Text]  
• Sandborn, W. J., Rutgeerts, P., Enns, R., Hanauer, S. B., Colombel, J.-F., Panaccione, R., D'Haens, G., Li, J., Rosenfeld, M. R., Kent, J. D., Pollack, P. F. (2007). Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab: A Randomized Trial. ANN INTERN MED 146: 829-838 [Abstract] [Full Text]  
• Zandi, M. S, Coles, A. J (2007). Notes on the kidney and its diseases for the neurologist. J. Neurol. Neurosurg. Psychiatry 78: 444-449 [Abstract] [Full Text]  
• Kuek, A., Hazleman, B. L, Ostor, A. J K (2007). Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad. Med. J. 83: 251-260 [Abstract] [Full Text]  
• Kolly, R., Thiel, M. A., Herrmann, T., Pluckthun, A. (2007). Monovalent antibody scFv fragments selected to modulate T-cell activation by inhibition of CD86-CD28 interaction. Protein Eng Des Sel 0: gzl058v1-8 [Abstract] [Full Text]  
• Russell, A S, Wallenstein, G V, Li, T, Martin, M C, Maclean, R, Blaisdell, B, Gajria, K, Cole, J C, Becker, J-C, Emery, P (2007). Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment. Ann Rheum Dis 66: 189-194 [Abstract] [Full Text]  
• Johnston, S. L (2007). Biologic therapies: what and when?. J. Clin. Pathol. 60: 8-17 [Abstract] [Full Text]  
• Hellmann, D. B., Imboden, J. B. (2006). Update in Rheumatology. ANN INTERN MED 145: 834-838 [Full Text]  
• Williams, E. L., Edwards, C. J. (2006). Patient preferences in choosing anti-TNF therapies-R1. Rheumatology (Oxford) 45: 1575-1576 [Full Text]  
• Bulwin, G.-C., Heinemann, T., Bugge, V., Winter, M., Lohan, A., Schlawinsky, M., Schulze, A., Walter, S., Sabat, R., Schulein, R., Wiesner, B., Veh, R. W., Lohler, J., Blumberg, R. S., Volk, H.-D., Utku, N. (2006). TIRC7 Inhibits T Cell Proliferation by Modulation of CTLA-4 Expression. J. Immunol. 177: 6833-6841 [Abstract] [Full Text]  
• Sweet, B. V. (2006). Abatacept.. Am J Health Syst Pharm 63: 2065-2077 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Emery, P, Keystone, E C, Schiff, M H, van Riel, P L C M, Weinblatt, M E, Weisman, M H (2006). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis 65: iii2-iii15 [Full Text]  
• Pucino, F. Jr., Harbus, P. T., Goldbach-Mansky, R. (2006). Use of biologics in rheumatoid arthritis: Where are we going?. Am J Health Syst Pharm 63: S19-S41 [Abstract] [Full Text]  
• Kremer, J. M., Genant, H. K., Moreland, L. W., Russell, A. S., Emery, P., Abud-Mendoza, C., Szechinski, J., Li, T., Ge, Z., Becker, J.-C., Westhovens, R. (2006). Effects of Abatacept in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis: A Randomized Trial.. ANN INTERN MED 144: 865-876 [Abstract] [Full Text]  
• Boers, M. (2006). Abatacept in rheumatoid arthritis: a new branch on the "biologics" tree.. ANN INTERN MED 144: 933-935 [Full Text]  
• (2005). New Drug for Rheumatoid Arthritis. JWatch General 2005: 4-4 [Full Text]