Abatacept: A costimulatory inhibitor for treatment of rheumatoid arthritis

Expert Opinion on Biological Therapy

Volumn 5, Issue 9, 2005, Pages 1245-1254

  Teng, Gim Gee ^a   Turkiewicz, Anthony M ^a   Moreland, Larry W ^a  

^a The University of Alabama at Birmingham   (United States)

Author keywords

Abatacept; Biological response modifiers; Costimulatory blockade; CTLA4 immunoglobulin; Rheumatoid arthritis

Indexed keywords

ABATACEPT; B7 ANTIGEN; BELATACEPT; CD28 ANTIGEN; CD86 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DISEASE MODIFYING ANTIRHEUMATIC DRUG; ETANERCEPT; HYBRID PROTEIN; INTERLEUKIN 1; INTERLEUKIN 2; INTERLEUKIN 6; METHOTREXATE; RECOMBINANT PROTEIN; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ANTIBODY; UNCLASSIFIED DRUG;

ANTIGEN BINDING; ANTIGEN PRESENTING CELL; CLINICAL TRIAL; DISEASE COURSE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; PATHOPHYSIOLOGY; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; T LYMPHOCYTE ACTIVATION;

ANIMALS; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; BIOLOGICAL RESPONSE MODIFIERS; DISEASE MODELS, ANIMAL; DRUG THERAPY, COMBINATION; HUMANS; IMMUNOCONJUGATES; INFUSIONS, INTRAVENOUS; LYMPHOCYTE ACTIVATION; METHOTREXATE; RANDOMIZED CONTROLLED TRIALS; T-LYMPHOCYTES;

EID: 24144434927     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.5.9.1245     Document Type: Review

References (60)

1. BRESNIHAN B, ALVARO-GRACIA JM, COBBY M et al.: Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. (1998) 41(12):2196-2204.
2. ST CLAIR EW, VAN DER HEIJDE DM, SMOLEN JS et al.: Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. (2004) 50(11):3432-3443.
3. KLARESKOG L, VAN DER HEIJDE DM, DE JAGER JP et al.: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet (2004) 363(9410):675-681.
4. LIPSKY PE, VAN DER HEIJDE DM, ST CLAIR EW et al.: 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(22):1594-1602.
5. MAINI RN, TAYLOR PC, PALEOLOG E et al.: Anti-tumour necrosis factor specific antibody (infliximab) treatment provides insights into the pathophysiology of rheumatoid arthritis. Ann. Rheum. Dis. (1999) 58(Suppl. 1):I56-I60.
6. MORELAND LW, BAUMGARTNER SW, SCHIFF MH et al.: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N. Engl. J. Med. (1997) 337(3):141-147.
7. KREMER JM, WESTHOVENS R, LEON M et al.: Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. (2003) 349(20):1907-1915. Phase IIb efficacy trial of abatacept with MTX in MTX non-responders.
8. FIRESTEIN GS, ZVAIFLER NJ: How important are T-cells in chronic rheumatoid synovitis? II. T cell-independent mechanisms from beginning to end. Arthritis Rheum. (2002) 46(2):298-308.
9. FIRESTEIN GS: The T-cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis. J. Clin. Invest. (2004) 114(4):471-474.
10. FOX DA: The role of T-cells in the immunopathogenesis of rheumatoid arthritis: new perspectives. Arthritis Rheum. (1997) 40(4):598-609.
11. GORONZY JJ, WEYAND CM: T-cell regulation in rheumatoid arthritis. Curr. Opin. Rheumatol. (2004) 16:212-217.
12. PANAYI GS: T-cell-dependent pathways in rheumatoid arthritis. Curr. Opin. Rheumatol. (1997) 9(3):236-240.
13. PANAYI GS, LANCHBURY JS, KINGSLEY GH: The importance of the T-cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum. (1992) 35(7):729-735.
14. FINCK BK, LINSLEY PS, WOFSY D: Treatment of murine lupus with CTLA4Ig. Science (1994) 265:1225-1227.
15. WEBB LM, WALMSLEY MJ, FELDMANN M: Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 costimulatory pathway: requirement for both B7-1 and B7-2. Eur. J. Immunol. (1996) 26:2320-2328.
16. KVIEN TK: Epidemiology and burden of illness of rheumatoid arthritis. Pharmacoeconomics (2004) 22(2Suppl.):1-12.
17. CHOY EH, PANAYI GS: Cytokine pathways and joint inflammation in rheumatoid arthritis. N. Engl. J. Med. (2001) 344(12):907-916.
18. LINSLEY PS, LEDBETTER JA: The role of the CD28 receptor during T-cell responses to antigen. Annu. Rev Immunol. (1993) 11:191-212.
19. SFIKAKIS PP, MAVRIKAKIS M: Adhesion and lymphocyte costimulatory molecules in systemic rheumatic diseases. Clin. Rheumatol. (1999) 18:317-327.
20. LINSLEY PS, GREENE JL, BRADY W, BAJORATH J, LEDBETTER JA, PEACH R: Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4. Immunity (1994) 1:793-801.
21. LIU MF, KOHSAKA H, SAKURAI H et al.: The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium. Arthritis Rheum. (1996) 39(1):110-114.
22. KOULOVA L, CLARK EA, SHU G, DUPONT B: The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T-cells. J. Exp. Med. (1991) 173:759-762.
23. MUELLER DL, JENKINS MK, SCHWARTZ RH: Clonal expansion, versus functional clonal inactivation: a costimulatory signaling pathway determines the outcome of T-cell antigen receptor occupancy. Annu. Rev. Immunol. (1989) 7:445-480.
24. SCHWART RH: T-cell anergy. Annu. Rev Immunol. (2003) 21:305-334.
25. MASZYNA F, HOFF H, KUNKEL D, RADBRUCH A, BRUNNER-WEINZIER MC: Diversity of clonal T-cell proliferation is mediated by differential expression of CD152(CTLA-4) on the cell surface of activated individual T lymphocytes. J. Immunol. (2003) 171:3459-3466.
26. GREENE JL, LEYTZE GM, EMSWILER J et al.: Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T-cell costimulatory interactions. J. Biol. Chem. (1996) 271(43):26762-26771.
27. BRUNNER MC, CHAMBERS CA, CHAN RK, HANKEJ, WINOTO A, ALLISONJP: CTLA-4 mediated inhibition of early events of T-cell proliferation. J. Immunol. (1999) 162:5813-5820.
28. BRUNNER-WEINZIER MC, HOFF H, BURMESTER GR: Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T-cell responses: implications for arthritis and autoimmune diseases. Arthritis Res. Ther. (2004) 6:45-54. Recent review of mechanisms of CTLA4.
29. FINGER EB, BLUESTONE JA: When ligand becomes receptor-tolerance via B7 signaling on DCs. Nat. Immunol. (2002) 3(11):1056-1057.
30. ABRAMS JR, KELLEY SL, HAYES E et al.: Blockade of T lymphocyte costimulation with Cytotoxic T Lymphocyte-associated Antigen 4-Immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, DCs and endothelial cells. J. Exp. Med. (2000) 192(5):681-694.
31. GROHMANN U, ORABONA C, FALLARINO F et al.: CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol. (2002) 3(11):1097-1101.
32. MELLOR AL, MUNN DH: Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol. Today (1999) 20(10):469-473.
33. FARBER DL, BINGAMAN AW, PATKE DS: Modulation of memory CD4 T cell function by CTLA4Ig. Ann. Rheum. Dis. (2004) 63(Suppl. 1):(pages not stated) - Discovery section.
34. REISER H, STADECKER MJ: Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune diseases. N. Engl. J. Med. (1996) 335(18):1369-1377.
35. SAYEGH MH, TURKA LA: The role of T-cell costimulatory activation pathways in transplant rejection. N. Engl. J. Med. (1998) 338(25):1813-1821.
36. LARSEN CP, PEARSON TC, ADAMS AB et al.: Rational development of LEA29Y (beletacept), a high affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am. J. Transplant. (2005) 5(3):443-453.
37. LENSCHOW DJ, HO S, SATTAR H et al.: Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J. Exp. Med. (1995) 181(3):1145-1155.
38. CROSS AH, GIRARD TJ, GIACOLETTO KS et al.: Long-term inhibition of murine experimental autoimmune encephalomyelitis using CTLA-4-Fc supports a key role for CD28 costimulation. J. Clin. Invest. (1995) 95(6):2783-2789.
39. QUATTROCCHI E, DALLMAN MJ, FELDMANN M: Adenovirus-mediated gene transfer of CTLA-4Ig fusion protein in the suppression of experimental autoimmune arthritis. Arthritis Rheum. (2000) 23(8):1688-1697.
40. MIHARA M, TAN I, CHUZHIN Y et al.: CTLA4Ig inhibits T-cell-dependent B-cell maturation in murine systemic lupus erythematosus. J. Clin. Invest. (2000) 106:91-101.
41. DAIKH DI, WOFSY D: Cutting edge: reversal of murine lupus with CTLA4Ig and cyclophosphamide. J. Immunol. (2001) 166:2913-2916.
42. SCHIFFER L, SINHA J, WANG X et al.: Short term administration of costimulatory blockade and cyclophosphamide induces remission of systemic lupus erythematosus nephritis in NZB/W F1 mice by a mechanism downstream of renal immune complex deposition. J. Immunol. (2003) 171:489-497. Insight into costimulatory blockade in a murine lupus model.
43. BALIGA P, CHAVIN KD, QIN L et al.: CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity. Transplantation (1994) 58(10):1082-1090.
44. KIRK AD, HARLAN DM, ARMSTRONG NN et al: CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc. Natl. Acad. Sci. USA (1997) 94(16):8789-8794.
45. LENSCHOW DJ, ZENG Y, THISTLETHWAITE JR et al.: Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA41g. Science (1992) 257(5071):789.
46. LIN H, BOLLING SF, LINSLEY PS et al.: Long-term acceptance of major histocompatibility complex mismatched cardiac allografts induced by CTLA4Ig plus donor-specific transfusion. J. Exp. Med. (1993) 178(5):1801-1806.
47. SAYEGH MH, AKALIN E, HANCOCK WW et al.: CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J. Exp. Med. (1995) 181(5):1869-1874.
48. ABRAMS JR, LEBWOHL MG, GUZZO CA et al.: CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J. Clin. Invest. (1999) 103(9):1243-1252. First experience with CTLA4Ig in humans.
49. VINCENTI F, LARSEN C, DURRBACH A et al.: Belatacept (LEA29Y) for maintenance immunosuppression in renal transplant recipients. N. Engl. J. Med. (2005) (In Press).
50. MORELAND LW, ALTEN R, VAN DEN BOSCH F et al.: 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(6):1470-1479. Phase I safety and efficacy of abatacept monotherapy.
51. NADLER S, TOWNSEND R, MIKESELL G et al.: Abatacept (CTLA4Ig; BMS-188667) significantly inhibits T-cell proliferation in vitro at clinically revelant concentrations. Ann. Rheum. Dis. (2004) 63(Suppl. 1):il42.
52. RUSSELL A, SHERGY W, SANY J, NUAMAH I, ARANDA R, BECKER J: Abatacept (CTLA4Ig; BMS-188667) treatment demonstrates rapid, consistent and sustained increases in ACR response rates over 1 year in patients with rheumatoid arthritis. Ann. Rheum. Dis. (2004) 63(Suppl. 1):i284.
53. WEISMAN M, DUREZ P, HALLEGUA D, NUAMAH I, VRATSANOS G, BECKER J: Abatacept (CTLA4Ig; BMS-188667) inhibits T-cell activation and the subsequent activation of inflammatory cell types, as demonstrated by sustained reductions in multiple inflammatory biomarkers. Ann. Rheum. Dis. (2004) 63(Suppl. 1):il38.
54. DOUGADOS M, WESTHOVENS R, RIEL PV, NUAMAH I, VRATSANOS G, BECKER J: Abatacept (CTLA4Ig; BMS-188667) plus methotrexate induces a rapid and sustained increase in remission rates in patients with active rheumatoid arthritis despite methotrexate treatment. Ann. Rheum. Dis. (2004) 63(Suppl. 1):i289.
55. SCOTT DL, ANTONI C, CHOY EH, VAN RIEL PC: Joint counts in routine practice. Rheumatology (Oxford) (2003) 42(8):919-923.
56. EMERY P, COMBE B, NUAMAH I et al.: Patients with rheumatoid arthritis treated with abatacept (CTLA4IG; BMS-188667) report rapid improvement in pain, disease activity and physical function. Ann. Rheum. Dis. (2004) 63(Suppl. 1):i525.
57. WEINBLATT M, SCHIFF M, GOLDMAN M, KREMER JM, BREAZNA A, BECKER JC: A pilot, multi-center, randomized, double-blind, placebo controlled trial of a co-stimulation blocker CTLA4Ig (2mg/kg) given monthly in combination with etanercept in active rheumatoid arthritis. Arthritis Rheum. (2002) 46:S204. First report of effectiveness of abatacept and etanercept combination.
58. KREMER JM, WESTHOVENS R, MORELAND LW et al.: Efficacy and safety of the selective co-stimulation modulator abatacept with methotrexate for treating rheumatoid arthritis: 1-year clinical and radiographic results from the Phase III AIM (Abatacept in Inadequate responders to Methotrexate) trial. N. Engl. J. Med. (2005) (In Press). Phase III study showing efficacy and radiographic outcomes in abatacept and MTX combination in MTX non-responders.
59. GENOVESE M, LUGGEN M, SCHIFF M et al.: Efficacy and safety of abatacept (CTLA4Ig), a selective costimulation modulator, in rheumatoid arthritis patients not responding adequately to anti-TNF-α therapy: results of the Phas III ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) Trial. Ann. Intern. Med. (2005) (In Press). Phase III study showing efficacy of abatacept and single DMARD in anti-TNF non-responders.
60. MORELAND LW, WEISMAN M, ALTEN R et al.: Abatacept (CTLA4Ig) in combination with methotrexate for the treatment of rheumatoid arthritis: Favorable safety and tolerability profile sustained over 2 years. Arthritis Rheum. (2004) 50(9 Suppl.):S563. 2-year safety report on abatacept.