Clinical Rheumatology

, Volume 32, Issue 1, pp 99–108 | Cite as

A multicenter, randomized, double-blind clinical trial of combination therapy with Anbainuo, a novel recombinant human TNFRII:Fc fusion protein, plus methotrexate versus methotrexate alone or Anbainuo alone in Chinese patients with moderate to severe rheumatoid arthritis

  • Xiao-Xiang Chen
  • Qing Dai
  • An-Bin Huang
  • Hua-Xiang Wu
  • Dong-Bao Zhao
  • Xing-Fu Li
  • Shao-Xian Hu
  • Nan-Ping Yang
  • Yi Tao
  • Jian-Hua Xu
  • Lin-Di Jiang
  • Chun-De Bao
Original Article

Abstract

This study aims to evaluate the clinical and radiological efficacy as well as safety profiles of Anbainuo, a recombinant human TNFRII:Fc fusion protein, combined with methotrexate (MTX) versus MTX alone or Anbainuo alone in the treatment of Chinese patients with moderate to severe rheumatoid arthritis (RA). In this 24-week, multicenter, double-blind, active comparator-controlled study, 396 RA patients were randomized into combination therapy group (Anbainuo plus MTX), Anbainuo group, or MTX group. Clinical response was assessed using the American College of Rheumatology (ACR)-N, ACR20, ACR50, ACR70, and van der Heijde modification of Sharp score, among which ACR-N and ACR20 were defined as primary major endpoints. After 24 weeks of treatment, the ACR-N in the combination therapy group (12.79 ± 9.24 %) was significantly higher than that in Anbainuo group (9.56 ± 11.16 %) and in MTX group (5.08 ± 11.1 %) (p = 0.00 and p = 0.00, respectively). Patients in Anbainuo group had significantly higher ACR-N than those in MTX group (p = 0.02). More patients in the combination therapy group (53.6 %) achieved ACR50 improvement response than those in the MTX group (30.8 %). ACR70 of combination therapy group (27.7 %) was significantly higher than that of Anbainuo group (15.8 %) and MTX group (7.70 %), with no significant difference between Anbainuo group and MTX group. DAS28-ESR in the combination therapy group was significantly reduced compared to either monotherapy groups. Moreover, DAS28-ESR was significantly lower in Anbainou group than in MTX group. The combination therapy group also showed significantly less radiographic progression than the MTX group (p = 0.03). The total adverse events (AE) in the combination group (40.9 %) was significantly higher than those in the MTX group (28.8 %) (p < 0.05). Anbainuo combined with MTX therapy can effectively control the disease activity and radiographic progression of RA, while the incidence of AE also increased compared to either Anbainuo or MTX.

Keywords

Methotrexate Rheumatoid arthritis TNF receptor II: Fc fusion protein 

Reference

  1. 1.
    Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 117(2):244–279. doi:10.1016/j.pharmthera.2007.10.001 PubMedCrossRefGoogle Scholar
  2. 2.
    Feldmann M, Maini RN (2003) Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 9(10):1245–1250. doi:10.1038/nm939 PubMedCrossRefGoogle Scholar
  3. 3.
    Weinblatt ME, Kremer JM, Bankhurst AD et al (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med Unbound 340(4):253–259CrossRefGoogle Scholar
  4. 4.
    Feldman M, Taylor P, Paleolog E, Brennan F, Maini R (1998) Anti-TNF alpha therapy is useful in rheumatoid arthritis and Crohn's disease: analysis of the mechanism of action predicts utility in other diseases. Transplant Proc 30(8):4126–4127PubMedCrossRefGoogle Scholar
  5. 5.
    Marzo-Ortega H, McGonagle D, O'Connor P et al (2001) Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy: a clinical and magnetic resonance imaging study. Arthritis Rheum 44(9):2112–2117PubMedCrossRefGoogle Scholar
  6. 6.
    Murdaca G, Colombo B, Puppo F (2011) Adalimumab for the treatment of immune-mediated diseases: an update on old and recent indications. Drugs Today 47(1):277, Barcelona, Spain: 1998PubMedGoogle Scholar
  7. 7.
    Klarenbeek NB, Guler-Yuksel M, van der Kooij SM et al (2011) The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis 70(6):1039–1046PubMedCrossRefGoogle Scholar
  8. 8.
    Ruiz GV, Jobanputra P, Burls A et al (2011) Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Cochrane Database Syst Rev 2:CD007649Google Scholar
  9. 9.
    Pappas DA, Bathon JM, Hanicq D, Yasothan U, Kirkpatrick P (2009) Golimumab. Nat Rev Drug Discov 8(9):695–696PubMedCrossRefGoogle Scholar
  10. 10.
    Hu D, Bao C, Chen S et al (2009) A comparison study of a recombinant tumor necrosis factor receptor: Fc fusion protein (rhTNFR: Fc) and methotrexate in treatment of patients with active rheumatoid arthritis in China. Rheumatol Int 29(3):297–303PubMedCrossRefGoogle Scholar
  11. 11.
    Moreland LW, Schiff MH, Baumgartner SW et al (1999) Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 130(6):478–486PubMedGoogle Scholar
  12. 12.
    Goffe B, Cather JC (2003) Etanercept: an overview. J Am Acad Dermatol 49(2 Suppl):S105–S111. doi:10.1016/mjd.2003.554 PubMedCrossRefGoogle Scholar
  13. 13.
    Kameda H, Ueki Y, Saito K et al (2010) Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol 20(6):531–538. doi:10.1007/s10165-010-0324-4 PubMedCrossRefGoogle Scholar
  14. 14.
    Knevel R, Schoels M, Huizinga T et al (2010) Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69(6):987PubMedCrossRefGoogle Scholar
  15. 15.
    Koncz T, Pentek M, Brodszky V, Ersek K, Orlewska E, Gulacsi L (2010) Adherence to biologic DMARD therapies in rheumatoid arthritis. Expert Opin Biol Ther (0):1-12Google Scholar
  16. 16.
    Bathon JM, Fleischmann RM, Van der Heijde D et al (2006) Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J Rheumatol 33(2):234PubMedGoogle Scholar
  17. 17.
    Chen S, Chen SL, Huang F et al (2010) A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of Etanercept in Chinese subjects with active rheumatoid arthritis receiving methotrexate. Chin J Rheumatol 7:450–455Google Scholar
  18. 18.
    Genovese MC, Bathon JM, Martin RW et al (2002) Etanercept versus methotrexate in patients with early rheumatoid arthritis: two years radiographic and clinical outcomes. Arthritis Rheum 46(6):1443–1450PubMedCrossRefGoogle Scholar
  19. 19.
    Klareskog L, van der Heijde D, de Jager JP et al (2004) 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 363(9410):675–681PubMedCrossRefGoogle Scholar
  20. 20.
    Nam J, Winthrop K, Van Vollenhoven R et al (2010) Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 69(6):976PubMedCrossRefGoogle Scholar
  21. 21.
    Bathon JM, Martin RW, Fleischmann RM et al (2000) A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med Unbound 343(22):1586–1593CrossRefGoogle Scholar
  22. 22.
    Emery P, Breedveld FC, Hall S et al (2008) Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 372(9636):375–382PubMedCrossRefGoogle Scholar
  23. 23.
    van der Heijde D, Klareskog L, Rodriguez-Valverde V et al (2006) Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum 54(4):1063–1074PubMedCrossRefGoogle Scholar
  24. 24.
    Kremer JM, Weinblatt ME, Bankhurst AD et al (2003) Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: continued observations. Arthritis Rheum 48(6):1493–1499PubMedCrossRefGoogle Scholar
  25. 25.
    van der Heijde D, Klareskog L, Landewé R et al (2007) Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 56(12):3928–3939PubMedCrossRefGoogle Scholar
  26. 26.
    Kameda H, Ueki Y, Saito K et al (2010) Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol 20(6):531–538PubMedCrossRefGoogle Scholar
  27. 27.
    Emery P, Breedveld F, van der Heijde D et al (2010) Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study. Arthritis Rheum 62(3):674–682PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2012

Authors and Affiliations

  • Xiao-Xiang Chen
    • 1
  • Qing Dai
    • 1
  • An-Bin Huang
    • 2
  • Hua-Xiang Wu
    • 3
  • Dong-Bao Zhao
    • 4
  • Xing-Fu Li
    • 5
  • Shao-Xian Hu
    • 6
  • Nan-Ping Yang
    • 7
  • Yi Tao
    • 8
  • Jian-Hua Xu
    • 9
  • Lin-Di Jiang
    • 10
  • Chun-De Bao
    • 1
  1. 1.Renji Hospital, School of MedicineAffiliated to Shanghai JiaoTong UniversityShanghaiChina
  2. 2.The Union HospitalAffiliated to Tongji UniversityHubei ProvinceChina
  3. 3.Second HospitalAffiliated to Zhejiang UniversityZhejiang ProvinceChina
  4. 4.Changhai HospitalAffiliated to Second Military Medical UniversityShanghaiChina
  5. 5.Qilu HospitalAffiliated to Shandong UniversityShandong ProvinceChina
  6. 6.Tongji HospitalAffiliated to Tongji UniversityHubei ProvinceChina
  7. 7.Huaxi HospitalAffiliated to Sichuan UniversitySichuan ProvinceChina
  8. 8.The Third HospitalAffiliated to Zhongshan Medical UniversityGuangdong ProvinceChina
  9. 9.The First HospitalAffiliated to Anhui medical UniversityAnhui ProvinceChina
  10. 10.Zhongshan HospitalAffiliated to Fudan UniversityShanghaiChina

Personalised recommendations