T-cell targeted therapies for rheumatoid arthritis
- Vibeke Strand, MD, MACR, FACP
Vibeke Strand, MD, MACR, FACP
- Adjunct Clinical Professor
- Stanford University School of Medicine
- Edward Keystone, MD
Edward Keystone, MD
- Professor of Medicine
- Mount Sinai Hospital, University of Toronto
- Section Editor
- Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
- Section Editor — Rheumatoid Arthritis
- Emeritus Professor of Rheumatology, Imperial College London
- Visiting Professor, Oxford University
The rationale for using T-cell targeted therapies for the treatment of rheumatoid arthritis (RA) stems from data that highlight the role of T cells in disease pathogenesis [1,2]. (See "Pathogenesis of rheumatoid arthritis".)
The data include:
●Animal models of inflammatory arthritis that demonstrate a crucial role for antigen-specific CD4+ T cells.
●The presence of an intense CD4+ T-cell infiltrate within rheumatoid synovium.
●The association between the inheritance of certain major histocompatibility complex (MHC) class II alleles and the development of RA. MHC class II alleles are required for antigen presentation to T cells. (See "HLA and other susceptibility genes in rheumatoid arthritis".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Lipsky PE, Davis LS. The central involvement of T cells in rheumatoid arthritis. The Immunologist 1998; 6:121.
- Kotzin BL, Kappler J. Targeting the T cell receptor in rheumatoid arthritis. Arthritis Rheum 1998; 41:1906.
- Moreland LW, Morgan EE, Adamson TC 3rd, et al. T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vbeta3, Vbeta14, and Vbeta17 peptides. Arthritis Rheum 1998; 41:1919.
- Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol 2015; 15:283.
- Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996; 14:233.
- Foy TM, Aruffo A, Bajorath J, et al. Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 1996; 14:591.
- Sayegh MH, Turka LA. The role of T-cell costimulatory activation pathways in transplant rejection. N Engl J Med 1998; 338:1813.
- Larsen CP, Elwood ET, Alexander DZ, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996; 381:434.
- 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; 43:1688.
- Orencia (abatacept) full prescribing information. http://packageinserts.bms.com/pi/pi_orencia.pdf (Accessed on October 10, 2011).
- Abatacept (Orencia) for rheumatoid arthritis. Med Lett Drugs Ther 2006; 48:17.
- Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev 2009; :CD007277.
- Maxwell LJ, Singh JA. Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol 2010; 37:234.
- Salliot C, Dougados M, Gossec L. Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials. Ann Rheum Dis 2009; 68:25.
- Yun H, Xie F, Delzell E, et al. Risk of hospitalised infection in rheumatoid arthritis patients receiving biologics following a previous infection while on treatment with anti-TNF therapy. Ann Rheum Dis 2015; 74:1065.
- Genovese MC, Covarrubias A, Leon G, et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum 2011; 63:2854.
- Keystone EC, Kremer JM, Russell A, et al. Abatacept in subjects who switch from intravenous to subcutaneous therapy: results from the phase IIIb ATTUNE study. Ann Rheum Dis 2012; 71:857.
- Nash P, Ludivico C, Delaet I, et al. Improvements in disease activity and physical function in patients with RA receiving subcutaneous abatacept in the presence or absence of an initial loading dose. Ann Rheum Dis 2011; 70(Suppl3):615.
- 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; 349:1907.
- Kremer JM, Genant HK, Moreland LW, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 2006; 144:865.
- Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 2005; 353:1114.
- Kremer JM, Genant HK, Moreland LW, et al. Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum 2008; 58:953.
- Kremer JM, Dougados M, Emery P, et al. 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.
- Weinblatt M, Combe B, Covucci A, et al. Safety of the selective costimulation modulator abatacept 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.
- Westhovens R, Robles M, Ximenes AC, et al. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. Ann Rheum Dis 2009; 68:1870.
- Bathon J, Robles M, Ximenes AC, et al. Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis 2011; 70:1949.
- Simon TA, Smitten AL, Franklin J, et al. Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment. Ann Rheum Dis 2009; 68:1819.
- Vincenti F, Luggen M. T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med 2007; 58:347.
- Kalunian KC, Davis JC Jr, Merrill JT, et al. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46:3251.
- Visvanathan S, Ramanujam M, Schoelch C, et al. FRI0231 Treatment with BI 655064 (antagonistic anti-CD40 antibody) modulates biomarkers associated with rheumatoid arthritis (RA). Ann Rheum Dis 2016; 75:517.
- Daniluk S, Ptaszynski R, Mueller-Ladner U, et al. SAT0147 Safety and efficacy of BI 655064, an antagonistic anti-CD40 antibody in rheumatoid arthritis (RA) patients. Ann Rheum Dis 2016; 75:718.
- Ridgeway W, Fathman CG. Anti-CD4 in the treatment of rheumatoid arthritis: A reappraisal. The Immunologist 1996; 4:203.
- Strand V, Kimberly R, Isaacs JD. Biologic therapies in rheumatology: lessons learned, future directions. Nat Rev Drug Discov 2007; 6:75.
- Epstein WV. Expectation bias in rheumatoid arthritis clinical trials. The anti-CD4 monoclonal antibody experience. Arthritis Rheum 1996; 39:1773.
- Choy EH, Pitzalis C, Cauli A, et al. Percentage of anti-CD4 monoclonal antibody-coated lymphocytes in the rheumatoid joint is associated with clinical improvement. Implications for the development of immunotherapeutic dosing regimens. Arthritis Rheum 1996; 39:52.
- Choy EH, Chikanza IC, Kingsley GH, et al. Treatment of rheumatoid arthritis with single dose or weekly pulses of chimaeric anti-CD4 monoclonal antibody. Scand J Immunol 1992; 36:291.
- Marchal G, Seman M, Milon G, et al. Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte. J Immunol 1982; 129:954.
- Moreland LW, Pratt PW, Bucy RP, et al. Treatment of refractory rheumatoid arthritis with a chimeric anti-CD4 monoclonal antibody. Long-term followup of CD4+ T cell counts. Arthritis Rheum 1994; 37:834.
- Moreland LW, Bucy RP, Jackson B, et al. Long term (5 years) follow up of RA patients treated with a depleting anti-CD4 mAb, cM-T412 (abstract). Arthritis Rheum 1996; 39:S244.
- Brett S, Baxter G, Cooper H, et al. Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H. Immunology 1996; 88:13.
- Ruderman EM, Weinblatt ME, Thurmond LM, et al. Synovial tissue response to treatment with Campath-1H. Arthritis Rheum 1995; 38:254.
- Matteson EL, Yocum DE, St Clair EW, et al. Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection. Arthritis Rheum 1995; 38:1187.
- Weinblatt ME, Maddison PJ, Bulpitt KJ, et al. CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study. Arthritis Rheum 1995; 38:1589.
- Schulze-Koops H, Davis LS, Haverty TP, et al. Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4. J Rheumatol 1998; 25:2065.
- Osman GE, Toda M, Kanagawa O, Hood LE. Characterization of the T cell receptor repertoire causing collagen arthritis in mice. J Exp Med 1993; 177:387.
- Haqqi TM, Qu XM, Anthony D, et al. Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice. J Clin Invest 1996; 97:2849.
- Paliard X, West SG, Lafferty JA, et al. Evidence for the effects of a superantigen in rheumatoid arthritis. Science 1991; 253:325.
- Cooper SM, Sriram S, Ranges GE. Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma. J Immunol 1988; 141:1958.
- St Clair EW, Cohen SB, Lee ML, et al. Treatment of rheumatoid arthritis with a DR4/1 peptide. J Rheumatol 2000; 27:1855.