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Abatacept: A Review in Rheumatoid Arthritis

Abstract

The biological DMARD (bDMARD) abatacept (Orencia®), a recombinant fusion protein, selectively modulates a co-stimulatory signal necessary for T-cell activation. In the EU, abatacept is approved for use in patients with highly active and progressive rheumatoid arthritis (RA) not previously treated with methotrexate. Abatacept is also approved for the treatment of moderate to severe active RA in patients with an inadequate response to previous therapy with at least one conventional DMARD (cDMARD), including methotrexate or a TNF inhibitor. In phase III trials, beneficial effects on RA signs and symptoms, disease activity, structural damage progression and physical function were seen with intravenous (IV) or subcutaneous (SC) abatacept regimens, including abatacept plus methotrexate in methotrexate-naive patients with early RA and poor prognostic factors, and abatacept plus methotrexate or other cDMARDs in patients with inadequate response to methotrexate or TNF inhibitors. Benefits were generally maintained during longer-term follow-up. Absolute drug-free remission rates following withdrawal of all RA treatments were significantly higher with abatacept plus methotrexate than with methotrexate alone. Both IV and SC abatacept were generally well tolerated, with low rates of immunogenicity. Current evidence therefore suggests that abatacept is a useful treatment option for patients with RA.

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References

  1. Chaudhari K, Rizvi S, Syed BA. Rheumatoid arthritis: current and future trends. Nat Rev Drug Discov. 2016;15(5):305–6.

    CAS  Article  PubMed  Google Scholar 

  2. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19.

    CAS  Article  PubMed  Google Scholar 

  3. Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3–15.

    Article  PubMed  Google Scholar 

  4. Smolen JS, Landewe R, Bijlsma JW, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2016;76:960–77.

    Article  Google Scholar 

  5. Korhonen R, Moilanen E. Abatacept, a novel CD80/86-CD28 T cell co-stimulation modulator, in the treatment of rheumatoid arthritis. Basic Clin Pharmacol Toxicol. 2009;104(4):276–84.

    CAS  Article  PubMed  Google Scholar 

  6. European Medicines Agency. Orencia (abatacept): EU summary of product characteristics. 2016. http://www.ema.europa.eu. Accessed 1 June 2017.

  7. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 2011;11(12):852–63.

    CAS  Article  PubMed  Google Scholar 

  8. Keating GM. Abatacept: a review of its use in the management of rheumatoid arthritis. Drugs. 2013;73(10):1095–119.

    CAS  Article  PubMed  Google Scholar 

  9. Cutolo M, Nadler SG. Advances in CTLA-4-Ig-mediated modulation of inflammatory cell and immune response activation in rheumatoid arthritis. Autoimmun Rev. 2013;12(7):758–67.

    CAS  Article  PubMed  Google Scholar 

  10. Bonelli M, Goschl L, Bluml S, et al. Abatacept (CTLA-4Ig) treatment reduces T cell apoptosis and regulatory T cell suppression in patients with rheumatoid arthritis. Rheumatology. 2016;55(4):710–20.

    Article  PubMed  Google Scholar 

  11. Platt AM, Gibson VB, Patakas A, et al. Abatacept limits breach of self-tolerance in a murine model of arthritis via effects on the generation of T follicular helper cells. J Immunol. 2010;185(3):1558–67.

    CAS  Article  PubMed  Google Scholar 

  12. Scarsi M, Ziglioli T, Airo P. Decreased circulating CD28-negative T cells in patients with rheumatoid arthritis treated with abatacept are correlated with clinical response. J Rheumatol. 2010;37(5):911–6.

    CAS  Article  PubMed  Google Scholar 

  13. Bonelli M, Ferner E, Göschl L, et al. Abatacept (CTLA-4Ig) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis. Arthritis Rheum. 2013;65(3):599–607.

    CAS  Article  PubMed  Google Scholar 

  14. Scarsi M, Paolini L, Ricotta D, et al. Abatacept reduces levels of switched memory B cells, autoantibodies, and immunoglobulins in patients with rheumatoid arthritis. J Rheumatol. 2014;41(4):666–72.

    CAS  Article  PubMed  Google Scholar 

  15. Weisman MH, Durez P, Hallegua D, et al. Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006;33(11):2162–6.

    CAS  PubMed  Google Scholar 

  16. Buch MH, Boyle DL, Rosengren S, et al. 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. 2009;68(7):1220–7.

    CAS  Article  PubMed  Google Scholar 

  17. Kukida Y, Kasahara A, Seno T, et al. Very early response to abatacept could be a predictive factor for repair of bone erosion in patients with rheumatoid arthritis assessed by MRI [abstract no. AB0256]. Ann Rheum Dis. 2016;75(Suppl 2):987.

    Article  Google Scholar 

  18. 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(12):1870–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 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(11):1949–56.

    CAS  Article  PubMed  Google Scholar 

  20. Smolen JS, Wollenhaupt J, Gomez-Reino JJ, et al. Attainment and characteristics of clinical remission according to the new ACR-EULAR criteria in abatacept-treated patients with early rheumatoid arthritis: new analyses from the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE). Arthritis Res Ther. 2015;17:157.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wells AF, Westhovens R, Reed DM, et al. Abatacept plus methotrexate provides incremental clinical benefits versus methotrexate alone in methotrexate-naive patients with early rheumatoid arthritis who achieve radiographic nonprogression. J Rheumatol. 2011;38(11):2362–8.

    CAS  Article  PubMed  Google Scholar 

  22. Emery P, Burmester GR, Bykerk VP, et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015;74(1):19–26.

    CAS  Article  PubMed  Google Scholar 

  23. Peterfy C, Burmester GR, Bykerk VP, et al. Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. Ann Rheum Dis. 2016;75(8):1501–5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Bykerk VP, Burmester G, Combe BG, et al. On drug and drug-free remission by baseline disease duration: abatacept versus methotrexate comparison in patients with early rheumatoid arthritis [abstract no. 554]. Arthritis Rheumatol. 2015;67(Suppl 10).

  25. 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(12):865–76.

    CAS  Article  PubMed  Google Scholar 

  26. 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(4):953–63.

    CAS  Article  PubMed  Google Scholar 

  27. Kremer JM, Peterfy C, Russell AS, et al. Longterm safety, efficacy, and inhibition of structural damage progression over 5 years of treatment with abatacept in patients with rheumatoid arthritis in the abatacept in inadequate responders to methotrexate trial. J Rheumatol. 2014;41(6):1077–87.

    CAS  Article  PubMed  Google Scholar 

  28. Kremer JM, Russell AS, Emery P, et al. Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial. Ann Rheum Dis. 2011;70(10):1826–30.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Schiff M, Keiserman M, Codding C, et al. 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. 2008;67(8):1096–103.

    CAS  Article  PubMed  Google Scholar 

  30. Schiff M, Keiserman M, Codding C, et al. Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study. Ann Rheum Dis. 2011;70(11):2003–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 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(10):2854–64.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Genovese MC, Tena CP, Covarrubias A, et al. Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial. J Rheumatol. 2014;41(4):629–39.

    CAS  Article  PubMed  Google Scholar 

  33. Weinblatt ME, Schiff M, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013;65(1):28–38.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Schiff M, Weinblatt ME, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014;73(1):86–94.

    CAS  Article  PubMed  Google Scholar 

  35. Genovese MC, Becker J-C, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor α inhibition. N Engl J Med. 2005;353(11):1114–23.

    CAS  Article  PubMed  Google Scholar 

  36. Genovese MC, Schiff M, Luggen M, et al. 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. 2008;67(4):547–54.

    CAS  Article  PubMed  Google Scholar 

  37. Genovese MC, Schiff M, Luggen M, et al. Longterm safety and efficacy of abatacept through 5 years of treatment in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitor therapy. J Rheumatol. 2012;39(8):1546–54.

    CAS  Article  PubMed  Google Scholar 

  38. Schiff M, Pritchard C, Huffstutter JE, et al. 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. 2009;68(11):1708–14.

    CAS  Article  PubMed  Google Scholar 

  39. 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(6):857–61.

    CAS  Article  PubMed  Google Scholar 

  40. Kaine J, Gladstein G, Strusberg I, et al. Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase IIIb ALLOW study). Ann Rheum Dis. 2012;71(1):38–44.

    CAS  Article  PubMed  Google Scholar 

  41. Sokolove J, Schiff M, Fleischmann R, et al. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016;75(4):709–14.

    CAS  Article  PubMed  Google Scholar 

  42. Choquette D, Bessette L, Haraoui B, et al. Six-year retention rates with abatacept vs TNF inhibitors in the treatment of rheumatoid arthritis: experience from the real-world Rhumadata clinical database and registry [abstract no. 488]. Arthritis Rheumatol. 2015;67(Suppl 10):705-7.

  43. Gottenberg JE, Morel J, Constantin A, et al. Long-term registry data in 4498 patients with rheumatoid arthritis indicate a similar safety but a different drug retention between abatacept, rituximab and tocilizumab [abstract no. 1998]. Arthritis Rheumatol. 2016;68(Suppl 10):2550–3.

  44. Alten R, Lorenz H-M, Nüßlein HG, et al. Body mass index does not impact abatacept retention in biologic-naive patients with rheumatoid arthritis who have poor prognostic factors: a 12-month interim analysis of an observational, prospective study [abstract no. 1589]. Arthritis Rheumatol. 2016;68(Suppl 10):1969–70.

  45. Gottenberg JE, Ravaud P, Cantagrel A, et al. Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the ‘Orencia and Rheumatoid Arthritis’ registry. Ann Rheum Dis. 2012;71(11):1815–9.

    CAS  Article  PubMed  Google Scholar 

  46. Lahaye C, Soubrier M, Mulliez A, et al. Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enrolled in the French Society of Rheumatology’s ORA registry. Rheumatology. 2016;55(5):874–82.

    Article  PubMed  Google Scholar 

  47. Nüßlein HG, Alten R, Galeazzi M, et al. Efficacy and prognostic factors of treatment retention with intravenous abatacept for rheumatoid arthritis: 24-month results from an international, prospective, real-world study. Clin Exp Rheumatol. 2016;34(3):489–99.

    PubMed  Google Scholar 

  48. Finckh A, Neto D, Iannone F, et al. The impact of patient heterogeneity and socioeconomic factors on abatacept retention in rheumatoid arthritis across nine European countries. RMD Open. 2015;1(1):e000040.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. Gottenberg JE, Courvoisier DS, Hernandez MV, et al. Brief report: association of rheumatoid factor and anti-citrullinated protein antibody positivity with better effectiveness of abatacept: results from the pan-European registry analysis. Arthritis Rheumatol. 2016;68(6):1346–52.

    CAS  Article  PubMed  Google Scholar 

  50. European Medicines Agency. CHMP extension of indication variation assessment report: Orencia (abatacept). 2016. http://www.ema.europa.eu. Accessed 1 June 2017.

  51. Weinblatt ME, Moreland LW, Westhovens R, et al. Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program. J Rheumatol. 2013;40(6):787–97.

    CAS  Article  PubMed  Google Scholar 

  52. Alten R, Kaine J, Keystone E, et al. Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment. Arthritis Rheumatol. 2014;66(8):1987–97.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. Simon TA, Askling J, Lacaille D, et al. Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment. Arthritis Res Ther. 2010;12(2):R67.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Salmon JH, Gottenberg JE, Ravaud P, et al. Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry. Ann Rheum Dis. 2016;75(6):1108–13.

    CAS  Article  PubMed  Google Scholar 

  55. Simon TA, Thompson A, Gandhi KK, et al. Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis. Arthritis Res Ther. 2015;17:212.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 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(12):1819–26.

    CAS  Article  PubMed  Google Scholar 

  57. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509.

    CAS  Article  PubMed  Google Scholar 

  58. Bristol-Myers Squibb. European Commission approves Bristol-Myers Squibb’s ORENCIA® (abatacept) for the treatment of highly active and progressive disease in adult patients with rheumatoid arthritis not previously treated with methotrexate [media release]. 6 Sep 2016. http://news.bms.com/.

  59. Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63(3):573–86.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Favalli EG, Becciolini A, Biggioggero M. Structural integrity versus radiographic progression in rheumatoid arthritis. RMD Open. 2015;1(Suppl 1):e000064.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Schiff M, Koo J, Jin E, et al. Usability and acceptability of the abatacept pre-filled autoinjector for the subcutaneous treatment of rheumatoid arthritis. Adv Ther. 2016;33(2):199–213.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. Schaeverbeke T, Truchetet ME, Kostine M, et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology. 2016;55(2):210–20.

    Article  PubMed  Google Scholar 

  63. Fleischmann R, Landewe R, Smolen JS. Review of head-to-head study designs in rheumatoid arthritis. Semin Arthritis Rheum. 2016;46:279–85.

    Article  Google Scholar 

  64. Guyot P, Taylor P, Christensen R, et al. Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis. Arthritis Res Ther. 2011;13:R204.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. Bergman GJ, Hochberg MC, Boers M, et al. Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs. Semin Arthritis Rheum. 2010;39(6):425–41.

    CAS  Article  PubMed  Google Scholar 

  66. Singh JA, Christensen R, Wells GA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. Sao Paulo Med J. 2010;128(5):309–10.

    Article  PubMed  Google Scholar 

  67. Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;(2):CD008794.

  68. Taylor PC, Moore A, Vasilescu R, et al. A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective. Rheumatol Int. 2016;36(5):685–95.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. Athanasakis K, Petrakis I, Kyriopoulos J. Investigating the value of abatacept in the treatment of rheumatoid arthritis. A systematic review of cost-effectiveness studies. ISRN Rheumatol. 2013. doi:10.1155/2013/256871.

  70. Gaultney J, Benucci M, Iannazzo S, et al. Trial-based cost-effectiveness of abatacept for rheumatoid arthritis patients in Italy. Expert Rev Pharmacoecon Outcomes Res. 2016;16(3):409–17.

    CAS  Article  PubMed  Google Scholar 

  71. Manders SH, Kievit W, Adang E, et al. Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial. Arthritis Res Ther. 2015;17:134.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

During the peer review process, the manufacturer of abatacept was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Correspondence to Hannah A. Blair.

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The preparation of this review was not supported by any external funding.

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Hannah Blair and Emma Deeks are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/0c48f0604545f656.

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The manuscript was reviewed by: C. Abud-Mendoza, Regional Unit of Rheumatology and Osteoporosis, Hospital Central Dr. Ignacio Morones Prieto, School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico; R. Alten, Department of Internal Medicine II, Rheumatology and Clinical Immunology, Schlosspark-Klinik, Charité-University Medicine Berlin, Berlin, Germany; M. Kostine, Département de Rhumatologie, Hôpital Pellegrin, Bordeaux, France; C. Richez, Département de Rhumatologie, Hôpital Pellegrin, Bordeaux, France; M. Soubrier, Service de Rhumatologie, CHU Clermont-Ferrand, Université Clermont Auvergne, Clermont-Ferrand, France.

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Blair, H.A., Deeks, E.D. Abatacept: A Review in Rheumatoid Arthritis. Drugs 77, 1221–1233 (2017). https://doi.org/10.1007/s40265-017-0775-4

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