Etanercept in the treatment of ankylosing spondylitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials, and the comparison of the Caucasian and Chinese population
- 497 Downloads
Background and purpose
Ankylosing spondylitis (AS) is a kind of rheumatic disease, leading to pain, fatigue, stiffness, and functional impairment, which seriously affects the quality of life. Etanercept, a fully human recombinant protein, has been applied for the treatment of AS. However, there has not been a systematic analysis for its efficacy and safety.
This meta-analysis of fourteen randomized, double-blind, placebo-controlled clinical trials with 1,570 participants was performed to investigate the efficacy and safety of etanercept, by means of calculating the overall relative risk, and to compare the different responses between the Caucasian population and the Chinese population.
Generally, there was sufficient evidence to prove that etanercept has its advantages in both disease activity controlling and symptoms relieving, especially for axial joints compared with peripheric joints, without higher incidence of serious adverse events.
Our preliminary analysis provided that the Caucasian population has better response to etanercept treatment, with more treatment-emergent adverse events. Further specially designed clinical trials need to be performed to investigate the different responses between axial and peripheric joints, also between different races.
KeywordsAnkylosing spondylitis Etanercept Meta-analysis
Conflict of interest
- 11.Gratacós J, Collado A, Filella X, Sanmartí R, Cañete J, Llena J, Molina R, Ballesta A, Muñoz-Gómez J (1994) Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 33(10):927–931PubMedCrossRefGoogle Scholar
- 12.Francois RJ, Neure L, Sieper J, Braun J (2006) Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumor necrosis factor in two patients with early disease and transforming growth factor in three more advanced cases. Ann Rheum Dis 65:713–720PubMedCrossRefGoogle Scholar
- 14.Brandt J, Khariouzov A, Listing J, Haibel H, Sörensen H, Grassnickel L, Rudwaleit M, Sieper J, Braun J (2003) Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum 48(6):1667–1675PubMedCrossRefGoogle Scholar
- 16.Braun J, Baraliakos X, Brandt J, Listing J, Zink A, Alten R et al (2005) Persistent clinical response to the anti-TNF-α antibody infliximab in patients with ankylosing spondylitis over 3 years. Heumatology 44:670–676Google Scholar
- 17.Braun J, Baraliakos X, Listing J, Fritz C, Alten R, Burmester G et al (2008) Persistent clinical efficacy and safety of anti-tumour necrosis factor therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response. Ann Rheum Dis 67:340–345PubMedCrossRefGoogle Scholar
- 18.Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W, Enbrel Ankylosing Spondylitis Study Group (2003) Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 48(11):3230–3236PubMedCrossRefGoogle Scholar
- 27.Higgins JPT, Green S (2008) Cochrane handbook for systematic reviews of interventions version 5.0.1 [updated September 2008]. The Cochrane CollaborationGoogle Scholar
- 31.Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P et al (2011) Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis 70(5):799–804PubMedCrossRefGoogle Scholar
- 32.Van der Heijde D, Da Silva JC, Dougados M, Geher P, van der Horst-Bruinsma I, Juanola X et al (2006) Etanercept study 314 investigators. Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 65(12):1572–1577PubMedCrossRefGoogle Scholar
- 33.Huang Feng, Zhang Jie, Huang JL, Wu DH, Li ZG, Chen SL et al (2010) A multicenter, double-blind, placebo-controlled, randomized, phase III clinical study of etanercept in treatment of ankylosing spondylitis. Chin J Intern Med 49(9):741–745Google Scholar
- 35.Wanders AJ, Gorman JD, Davis JC, Landewe RB, van der Heijde DM (2004) Responsiveness and discriminative capacity of the assessments in ankylosing spondylitis disease-controlling antirheumatic therapy core set and other outcome measures in a trial of etanercept in ankylosing spondylitis. Arthritis Rheum 51(1):1–8PubMedCrossRefGoogle Scholar
- 36.Wang LS, Huang F, Zhang JL, Deng XH, Zhang YM, Zhang LY et al (2007) A cohort analysis of safety tumor necrosis factor-α antagonists in the treatment of Chinese patients with ankylosing spondylitis. Chin J New Drugs 16(7):556–561Google Scholar
- 37.Zhang H, Deng XH, Zhang YM, Zhang JL, Huang F (2008) Studies on safety of etanercept in treatment of ankylosing spondylitis. Adverse Drug React J 10(6):396–399Google Scholar
- 38.Zhang YM, Li XL, Wu HL, Zhang J (2009) Short-term safety of etanercept therapy in patients with ankylosing spondylitis. Chin J Drug Appl Monit 6(1):4–13Google Scholar
- 39.Zhang J (2010) Initiatory approach on clinical assessment and evaluation of etanercept in the treatment of ankylosing spondylitis. Graduation dissertation for Master’s degreeGoogle Scholar
- 44.Braun J, Landewe R, Hermann KG, Han J, Yan S, Williamson P, for the ASSERT Study Group et al (2006) Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study. Arthritis Rheum 54:1646–1652PubMedCrossRefGoogle Scholar
- 45.McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, et al (2007) Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol Assess 11(28):1–158, iii–ivGoogle Scholar