abatacept

Summary

Summary: A fusion protein immunoconjugate of the extracellular domain of CTLA4 and the Fc domain of human IgG1. It functions as a T-cell co-stimulation blocker that inhibits TNF-ALPHA and prevents the activation of T-LYMPHOCYTES. It is used in the treatment of RHEUMATOID ARTHRITIS.

Top Publications

  1. Canete J, Celis R, Hernandez V, Pablos J, Sanmarti R. Synovial immunopathological changes associated with successful abatacept therapy in a case of severe refractory psoriatic arthritis. Ann Rheum Dis. 2010;69:935-6 pubmed publisher
  2. Wadström H, Frisell T, Askling J. Malignant Neoplasms in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors, Tocilizumab, Abatacept, or Rituximab in Clinical Practice: A Nationwide Cohort Study From Sweden. JAMA Intern Med. 2017;177:1605-1612 pubmed publisher
  3. Singh J, Hossain A, Mudano A, Tanjong Ghogomu E, Suarez Almazor M, Buchbinder R, et al. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2017;5:CD012657 pubmed publisher
    ..To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small ..
  4. Mease P, Gottlieb A, van der Heijde D, Fitzgerald O, Johnsen A, Nys M, et al. Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis. Ann Rheum Dis. 2017;76:1550-1558 pubmed publisher
    To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA)...
  5. Melilli E, Bestard Matamoros O, Manonelles Montero A, Sala Bassa N, Mast R, Grinyó Boira J, et al. Arterial stiffness in kidney transplantation: a single center case-control study comparing belatacept versus calcineurin inhibitor immunosuppressive based regimen. Nefrologia. 2015;35:58-65 pubmed publisher
    ..008; P=0.045). Belatacept-based maintenance immunosuppression could improve kidney transplant recipient’s survival by reducing cardiovascular events related to stiffness. ..
  6. . Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol. 2014;66:3096-104 pubmed publisher
    To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce "clinical tolerance," defined as sustained clinical quiescence of ..
  7. Crnkic Kapetanovic M, Saxne T, Jonsson G, Truedsson L, Geborek P. Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis. Arthritis Res Ther. 2013;15:R171 pubmed publisher
    The objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients ..
  8. Wakikawa A, Utsuyama M, Hirokawa K. Altered expression of various receptors on T cells in young and old mice after mitogenic stimulation: a flow cytometric analysis. Mech Ageing Dev. 1997;94:113-22 pubmed
    ..Lower expression of TCR, IL-2 receptors and co-stimulatory molecules in T cells from old mice could be responsible for the impaired proliferation after mitogenic stimulation. ..
  9. Fukuyo S, Nakayamada S, Iwata S, Kubo S, Saito K, Tanaka Y. Abatacept therapy reduces CD28+CXCR5+ follicular helper-like T cells in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2017;35:562-570 pubmed
    The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT...

More Information

Publications32

  1. Mai H, Boeffard F, Longis J, Danger R, Martinet B, Haspot F, et al. IL-7 receptor blockade following T cell depletion promotes long-term allograft survival. J Clin Invest. 2014;124:1723-33 pubmed publisher
    ..Our data suggest that IL-7R blockade following T cell depletion has potential as a robust, immunosuppressive therapy in transplantation. ..
  2. Germanidis G, Hytiroglou P, Zakalka M, Settas L. Reactivation of occult hepatitis B virus infection, following treatment of refractory rheumatoid arthritis with abatacept. J Hepatol. 2012;56:1420-1 pubmed publisher
  3. Baliga P, Chavin K, Qin L, Woodward J, Lin J, Linsley P, et al. CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity. Transplantation. 1994;58:1082-90 pubmed
    ..The most efficacious time of administration is during priming of the immune response at the time of antigen presentation. ..
  4. Veale D. New therapies and new goals for psoriatic arthritis. Arthritis Rheum. 2011;63:874-6 pubmed publisher
  5. Pozzilli P, Strollo R. Immunotherapy for Type 1 diabetes: getting beyond a negative first impression. Immunotherapy. 2012;4:655-8 pubmed publisher
  6. Verstappen G, Meiners P, Corneth O, Visser A, Arends S, Abdulahad W, et al. Attenuation of Follicular Helper T Cell-Dependent B Cell Hyperactivity by Abatacept Treatment in Primary Sjögren's Syndrome. Arthritis Rheumatol. 2017;69:1850-1861 pubmed publisher
    To assess the effect of abatacept (CTLA-4Ig), which limits T cell activation, on homeostasis of CD4+ T cell subsets and T cell-dependent B cell hyperactivity in patients with primary Sjögren's syndrome (SS)...
  7. Kälble F, Schaier M, Schafer S, Süsal C, Zeier M, Sommerer C, et al. An update on chemical pharmacotherapy options for the prevention of kidney transplant rejection with a focus on costimulation blockade. Expert Opin Pharmacother. 2017;18:799-807 pubmed publisher
  8. Record J, Beukelman T, Cron R. Combination therapy of abatacept and anakinra in children with refractory systemic juvenile idiopathic arthritis: a retrospective case series. J Rheumatol. 2011;38:180-1 pubmed publisher
  9. Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000;192:295-302 pubmed
    ..Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases. ..
  10. Krummey S, Cheeseman J, Conger J, Jang P, Mehta A, Kirk A, et al. High CTLA-4 expression on Th17 cells results in increased sensitivity to CTLA-4 coinhibition and resistance to belatacept. Am J Transplant. 2014;14:607-14 pubmed
    ..These data highlight important differences in costimulatory and coinhibitory requirements of CD4+ memory subsets, and demonstrate that the heterogeneity of pathogen-derived memory has implications for immunomodulation strategies. ..
  11. Furst D, Keystone E, Fleischmann R, Mease P, Breedveld F, Smolen J, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis. 2010;69 Suppl 1:i2-29 pubmed publisher
  12. Haraldsson B. A new era of podocyte-targeted therapy for proteinuric kidney disease. N Engl J Med. 2013;369:2453-4 pubmed publisher
  13. Riley J, Schlienger K, Blair P, Carreno B, Craighead N, Kim D, et al. Modulation of susceptibility to HIV-1 infection by the cytotoxic T lymphocyte antigen 4 costimulatory molecule. J Exp Med. 2000;191:1987-97 pubmed
    ..Finally, CTLA-4 antibodies decrease the susceptibility of antigen-activated CD4 T cells to HIV, suggesting a potential approach to prevent or limit viral spread in HIV-1-infected individuals. ..
  14. Fanouriakis A, Vassilopoulos D, Repa A, Boumpas D, Sidiropoulos P. Hepatitis B reactivation following treatment with abatacept in a patient with past hepatitis B virus infection. Rheumatology (Oxford). 2014;53:195-6 pubmed publisher
  15. Blair H, Deeks E. Abatacept: A Review in Rheumatoid Arthritis. Drugs. 2017;77:1221-1233 pubmed publisher
    The biological DMARD (bDMARD) abatacept (Orencia®), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation...
  16. Samson M, Bonnotte B. [From pathogenesis of giant cell arteritis to new therapeutic targets]. Rev Med Interne. 2017;38:670-678 pubmed publisher
    ..Thanks to these advances in the knowledge of GCA pathogenesis, new therapeutic targets have emerged such as blockade of the activation of T cells or inhibition of the interleukin-6 (IL-6), IL-12/23 or IL-1? pathways. ..
  17. Furst D, Keystone E, Braun J, Breedveld F, Burmester G, De Benedetti F, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2011. Ann Rheum Dis. 2012;71 Suppl 2:i2-45 pubmed publisher
  18. Lon H, Liu D, Dubois D, Almon R, Jusko W. Modeling pharmacokinetics/pharmacodynamics of abatacept and disease progression in collagen-induced arthritic rats: a population approach. J Pharmacokinet Pharmacodyn. 2013;40:701-12 pubmed
    The PK/PD of abatacept, a selective T cell co-stimulation modulator, was examined in rats with collagen-induced arthritis (CIA) using a nonlinear mixed effect modeling approach...
  19. Furst D, Keystone E, Braun J, Breedveld F, Burmester G, De Benedetti F, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2010. Ann Rheum Dis. 2011;70 Suppl 1:i2-36 pubmed publisher
  20. Harrold L, Litman H, Connolly S, Kelly S, Hua W, Alemao E, et al. A window of opportunity for abatacept in RA: is disease duration an independent predictor of low disease activity/remission in clinical practice?. Clin Rheumatol. 2017;36:1215-1220 pubmed publisher
    ..predicts treatment response among biologic-naïve patients with rheumatoid arthritis (RA) initiating abatacept in clinical practice...
  21. Walker L, Gulbranson Judge A, Flynn S, Brocker T, Raykundalia C, Goodall M, et al. Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. J Exp Med. 1999;190:1115-22 pubmed
    ..These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation. ..
  22. Gärdby E, Kagrdic D, Kjerrulf M, Bromander A, Vajdy M, Hornquist E, et al. The influence of costimulation and regulatory CD4+ T cells on intestinal IgA immune responses. Dev Immunol. 1998;6:53-60 pubmed
    ..Thus, despite the various deficiencies in CD4+ T-cell functions seemingly intact IgA B-cell development was observed. ..
  23. Keser G, Aksu K. What is new in management of Takayasu arteritis?. Presse Med. 2017;46:e229-e235 pubmed publisher
    ..Besides, there are potential new therapeutic targets which may be promising in the future for medical treatment of TAK. Finally, new trends in endovascular interventions for management of TAK deserve attention. ..