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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2008

01-10-2008 | Review

Abatacept in the treatment of rheumatoid arthritis

Authors: Maya H Buch, Edward M Vital, Paul Emery

Published in: Arthritis Research & Therapy | Special Issue 1/2008

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Abstract

T-cell biology has regained importance in the pathogenesis of rheumatoid arthritis. Despite the significant improvements associated with the introduction of tumor necrosis factor-α blockade, reasonable proportions of failures and suboptimal responses have been reported, necessitating a search for alternative targeted therapies. This has included drug therapy designed to interrupt T-cell activation via the co-stimulation pathway. Abatacept is a recombinant fusion protein that blocks the co-stimulatory signal mediated by the CD28-CD80/86 pathway, which is required for T-cell activation. Several clinical trials have confirmed the safety and efficacy of this drug in the treatment of rheumatoid arthritis. This review summarizes the clinical data supporting this line of treatment and considers the safety and efficacy data from phase II and III trials.
Literature
1.
Calin A, Elswood J, Klouda PT: Destructive arthritis, rheumatoid factor, and HLA-DR4. Susceptibility versus severity, a case-control study. Arthritis Rheum. 1989, 32: 1221-1225.CrossRefPubMed
2.
Winchester R: The molecular basis of susceptibility to rheumatoid arthritis. Adv Immunol. 1994, 56: 389-466.CrossRefPubMed
3.
Banerjee S, Webber C, Poole AR: The induction of arthritis in mice by the cartilage proteoglycan aggrecan: roles of CD4+ and CD8+ T cells. Cell Immunol. 1992, 144: 347-357.CrossRefPubMed
4.
Breedveld FC, Dynesius-Trentham R, de Sousa M, Trentham DE: Collagen arthritis in the rat is initiated by CD4+ T cells and can be amplified by iron. Cell Immunol. 1989, 121: 1-12.CrossRefPubMed
5.
Mima T, Saeki Y, Ohshima S, Nishimoto N, Matsushita M, Shimizu M, Kobayashi Y, Nomura T, Kishimoto T: Transfer of rheumatoid arthritis into severe combined immunodeficient mice. The pathogenetic implications of T cell populations oligoclonally expanding in the rheumatoid joints. J Clin Invest. 1995, 96: 1746-1758.PubMedCentralCrossRefPubMed
6.
Van Boxel JA, Paget SA: Predominantly T-cell infiltrate in rheumatoid synovial membranes. N Engl J Med. 1975, 293: 517-520.CrossRefPubMed
7.
Kraan MC, Haringman JJ, Weedon H, Barg EC, Smith MD, Ahern MJ, Smeets TJ, Breedveld FC, Tak PP: T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with joint damage in patients with recent onset rheumatoid arthritis. Ann Rheum Dis. 2004, 63: 483-488.PubMedCentralCrossRefPubMed
8.
Feldmann M, Brennan FM, Maini RN: Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996, 14: 397-440.CrossRefPubMed
9.
Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P: Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999, 354: 1932-1939.CrossRefPubMed
10.
Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, Ettlinger RE, Cohen S, Koopman WJ, Mohler K, Widmer MB, Blosch CM: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med. 1997, 337: 141-147.CrossRefPubMed
11.
Lipsky PE, Heijde van der DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN, Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000, 343: 1594-1602.CrossRefPubMed
12.
Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA: CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991, 174: 561-569.CrossRefPubMed
13.
Alegre ML, Frauwirth KA, Thompson CB: T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol. 2001, 1: 220-228.CrossRefPubMed
14.
Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA: Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science. 1992, 257: 789-792.CrossRefPubMed
15.
Finck BK, Linsley PS, Wofsy D: Treatment of murine lupus with CTLA4Ig. Science. 1994, 265: 1225-1227.CrossRefPubMed
16.
Reynolds J, Tam FW, Chandraker A, Smith J, Karkar AM, Cross J, Peach R, Sayegh MH, Pusey CD: CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest. 2000, 105: 643-651.PubMedCentralCrossRefPubMed
17.
Webb LM, Walmsley MJ, Feldmann M: Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 co-stimulatory pathway: requirement for both B7-1 and B7-2. Eur J Immunol. 1996, 26: 2320-2328.CrossRefPubMed
18.
Abrams JR, Lebwohl MG, Guzzo CA, Jegasothy BV, Goldfarb MT, Goffe BS, Menter A, Lowe NJ, Krueger G, Brown MJ, Weiner RS, Birkhofer MJ, Warner GL, Berry KK, Linsley PS, Krueger JG, Ochs HD, Kelley SL, Kang S: CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999, 103: 1243-1252.PubMedCentralCrossRefPubMed
19.
Moreland LW, Alten R, Bosch Van den F, Appelboom T, Leon M, Emery P, Cohen S, Luggen M, Shergy W, Nuamah I, Becker JC: Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002, 46: 1470-1479.CrossRefPubMed
20.
Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, Russell A, Dougados M, Emery P, Nuamah IF, Williams GR, Becker JC, Hagerty DT, Moreland LW: Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003, 349: 1907-1915.CrossRefPubMed
21.
Kremer JM, Dougados M, Emery P, Durez P, Sibilia J, Shergy W, Steinfeld S, Tindall E, Becker JC, Li T, Nuamah IF, Aranda R, Moreland LW: Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005, 52: 2263-2271.CrossRefPubMed
22.
Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R: Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006, 144: 865-876.CrossRefPubMed
23.
Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Teng J, Becker JC, Westhovens R: Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abat-acept and methotrexate. Arthritis Rheum. 2008, 58: 953-963.CrossRefPubMed
24.
Heijde van der DM, van Riel PL, Nuver-Zwart IH, Putte van de LB: Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3-year follow-up. Lancet. 1990, 335: 539-CrossRefPubMed
25.
Genant HK: Methods of assessing radiographic change in rheumatoid arthritis. Am J Med. 1983, 75: 35-47.CrossRefPubMed
26.
Genant HK, Jiang Y, Peterfy C, Lu Y, Redei J, Countryman PJ: Assessment of rheumatoid arthritis using a modified scoring method on digitized and original radiographs. Arthritis Rheum. 1998, 41: 1583-1590.CrossRefPubMed
27.
Genant HK, Peterfy CG, Westhovens R, Becker JC, Aranda R, Vratsanos G, Teng J, Kremer JM: Abatacept inhibits structural damage progression in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis. 2007,
28.
Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, Saldate C, Li T, Aranda R, Becker J-C, Lin C, Cornet PLN, Dougados M: Efficacy and safety of abatacept or inflix-imab 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. 2008, 67: 1096-1103.PubMedCentralCrossRefPubMed
29.
Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M: Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005, 353: 1114-1123.CrossRefPubMed
30.
Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, Li T, Schmidely N, Le Bars M, Dougados M: 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-TNF therapy. Ann Rheum Dis. 2008, 67: 547-554.CrossRefPubMed
31.
Weinblatt M, Schiff M, Goldman A, Kremer J, Luggen M, Li T, Chen D, Becker JC: Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis. 2007, 66: 228-234.PubMedCentralCrossRefPubMed
32.
Russell AS, Wallenstein GV, Li T, Martin MC, Maclean R, Blaisdell B, Gajria K, Cole JC, Becker JC, Emery P: Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment. Ann Rheum Dis. 2007, 66: 189-194.PubMedCentralCrossRefPubMed
33.
Westhovens R, Cole JC, Li T, Martin M, Maclean R, Lin P, Blaisdell B, Wallenstein GV, Aranda R, Sherrer Y: Improved health-related quality of life for rheumatoid arthritis patients treated with abatacept who have inadequate response to anti-TNF therapy in a double-blind, placebo-controlled, multicentre randomized clinical trial. Rheumatology. 2006, 45: 1238-1246.CrossRefPubMed
34.
Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E: Safety of the selective costimulation modulator abat-acept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: a one-year randomized, placebo-controlled study. Arthritis Rheum. 2006, 54: 2807-2816.CrossRefPubMed
35.
Hyrich KL, Silman AJ, Watson KD, Symmons DP: Anti-tumour necrosis factor alpha therapy in rheumatoid arthritis: an update on safety. Ann Rheum Dis. 2004, 63: 1538-1543.PubMedCentralCrossRefPubMed
36.
Dass S, Vital EM, Emery P: Development of psoriasis after B cell depletion with rituximab. Arthritis Rheu. 2007, 56: 2715-2718.CrossRef
37.
Haggerty HG, Abbott MA, Reilly TP, DeVona DA, Gleason CR, Tay L, Dodge R, Aranda R: Evaluation of immunogenicity of the T cell costimulation modulator abatacept in patients treated for rheumatoid arthritis. J Rheumatol. 2007, 34: 2365-2373.PubMed
38.
Sibilia J, Westhovens R: Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2007, 25 (suppl 46): S46-S56.PubMed
39.
Judge TA, Tang A, Spain LM, Deans-Gratiot J, Sayegh MH, Turka LA: The in vivo mechanism of action of CTLA4Ig. J Immunol. 1996, 156: 2294-2299.PubMedCentralPubMed
40.
Fontenot AP, Gharavi L, Bennett SR, Canavera SJ, Newman LS, Kotzin BL: CD28 costimulation independence of target organ versus circulating memory antigen-specific CD4+ T cells. J Clin Invest. 2003, 112: 776-784.PubMedCentralCrossRefPubMed
41.
Shimoyama Y, Nagafuchi H, Suzuki N, Ochi T, Sakane T: Synovium infiltrating T cells induce excessive synovial cell function through CD28/B7 pathway in patients with rheumatoid arthritis. J Rheumatol. 1999, 26: 2094-2101.PubMed
42.
Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, Vratsanos G, Zhou Y, Moreland LW: Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006, 33: 2162-2166.PubMed
43.
Davis PM, Nadler SG, Stetsko DK, Suchard SJ: Abatacept modulates human dendritic cell-stimulated T-cell proliferation and effector function independent of IDO induction. Clin Immunol. 2008, 126: 38-47.CrossRefPubMed
44.
Buch MH, Boyle D, Saleem B, Rosengren S, Reece R, Rhodes L, Radjenovic A, English A, Tang H, Vratsanos G, O'Connor P, Firestein GS, Emery P: Mode of action of abatacept in rheumatoid arthritis patients having failed TNF blockade: a histological, gene expression and dynamic MRI study. Arthritis Rheum. 2005, 52: S1164-
45.
Tak PP, Taylor PC, Breedveld FC, Smeets TJ, Daha MR, Kluin PM, Meinders AE, Maini RN: Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum. 1996, 39: 1077-1081.CrossRefPubMed
46.
Smeets TJ, Kraan MC, van Loon ME, Tak PP: Tumor necrosis factor alpha blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue. Arthritis Rheum. 2003, 48: 2155-2162.CrossRefPubMed
47.
Buch MH, Bingham SJ, Seto Y, McGonagle D, Bejarano V, White J, Emery P: Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor alpha blockade. Arthritis Rheum. 2004, 50: 725-728.CrossRefPubMed
48.
Davidson A, Diamond B, Wofsy D, Daikh D: Block and tackle: CTLA4Ig takes on lupus. Lupus. 2005, 14: 197-203.CrossRefPubMed
49.
Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, Hagerty D, Levy E, Zhou W, Natarajan K, Charpentier B, Belatacept Study Group: Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005, 353: 770-781.CrossRefPubMed
Metadata
Title
Abatacept in the treatment of rheumatoid arthritis
Authors
Maya H Buch
Edward M Vital
Paul Emery
Publication date
01-10-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue Special Issue 1/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2416

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