Adalimumab in ankylosing spondylitis: an evidence-based review of its place in therapy

Stephanie Hennigan, Christoph Ackermann, Arthur Kavanaugh, Stephanie Hennigan, Christoph Ackermann, Arthur Kavanaugh

Abstract

Introduction: Ankylosing spondylitis (AS) is an idiopathic chronic inflammatory disease that has prominent effects on the spine and peripheral joints. In addition, extraarticular manifestations such as enthesitis and acute anterior uveitis may be clinically important. In recent years, the therapy of AS has changed, largely due to the introduction of inhibitors of the proinflammatory cytokine tumor necrosis factor (TNF). Adalimumab, a human monoclonal antibody specifically for TNF, is the most recent of the TNF blocking agents that have been approved for the treatment of active, nonsteroidal antiinflammatory drug (NSAID)-refractory patients with AS.

Aims: To evaluate the evidence for the therapeutic value of adalimumab in ankylosing spondylitis.

Evidence review: There is clear evidence that adalimumab, administered 40 mg subcutaneously every 2 weeks, substantially improves the signs and symptoms of NSAID-refractory, active AS when compared with placebo treatment. There is ample evidence that adalimumab causes significant improvements in physical health status and overall AS-specific, health-related quality of life and physical functioning, which consequently leads to better work productivity. There is substantial evidence that adalimumab improves spinal and sacroiliac joint inflammation in AS patients. Initial results from clinical trials suggest that there is no increased risk of serious infections or malignancies in adalimumab-treated patients with AS. The most common adverse events were injection-site reactions. Limited economic evidence suggests that adalimumab 40 mg may be cost effective when used according to current valid treatment guidelines.

Place in therapy: Adalimumab is an effective treatment for patients with active AS.

Keywords: TNF inhibitor; adalimumab; ankylosing spondylitis; evidence; treatment.

References

    1. Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylosing Spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001;44:1876–1886.
    1. Anon Ankylosing Spondylitis Prescribing Information. Humira. 2007. Available at: (accessed September 22, 2007).
    1. Anon Clinical Guidelines: Ankylosing Spondylitis. BSR Statement on Adalimumab for Ankylosing Spondylitis. The British Society of Rheumatology. August 2006. Available at: (accessed September 22, 2007).
    1. Baraliakos X, Listing J, Brandt J, et al. Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab. Arthritis Res Ther. 2005;7:439–444.
    1. Boonen A. A review of work-participation, cost-of-illness and cost-effectiveness studies in ankylosing spondylitis. Nat Clin Pract Rheumatol. 2006;2:546–553.
    1. Boonen A, van der Heijde D, Landewé R, et al. Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries. Ann Rheum Dis. 2003;62:732–740.
    1. Botteman MF, Hay JW, Luo MP, et al. Cost effectiveness of adalimumab for the treatment of ankylosing spondylitis in the United Kingdom. Rheumatology. 2007;46:1320–1328. (advance access publication June 2007).
    1. Brandt J, Khariouzov A, Listing J, et al. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum. 2003;48:1667–1675.
    1. Brandt J, Listing J, Sieper J, et al. Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis. Ann Rheum Dis. 2004;63:1438–1444.
    1. Braun J, Zochling J, Baraliakos X, et al. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann Rheum Dis. 2006a;65:1147–1153.
    1. Braun J, Davis J, Dougados M, et al. First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2006b;65:316–320.
    1. Braun J, Baraliakos X, Listing J, et al. Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum. 2007;57:639–647.
    1. Calin A, Garratt S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 1994;21:2281–2285.
    1. Carrasco JA, Martos J, Guijo V, et al. Adalimumab achieve significant improvement in active ankylosing spondylitis patients assessed by magnetic resonance imaging. Ann Rheum Dis. 2007;66:391.
    1. Chen J, Liu C. Is sulfasalazine effective in ankylosing spondylitis? A systematic review of randomized controlled trials. J Rheumatol. 2006;33:722–731.
    1. Chen J, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev. 2006;4:CD004524.
    1. Chorus AM, Miedema HS, Boonen A, Van Der Linden S. Quality of life and work in patients with rheumatoid arthritis and ankylosing spondylitis of working age. Ann Rheum Dis. 2003;62:1178–1184.
    1. Clegg DO, Reda DJ, Abdellatif M. Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondyloarthropathies: a Department of Veterans Affairs cooperative study. Arthritis Rheum. 1999;42:2325–2329.
    1. Dagfinrud H, Mengshoel AM, Hagan KB, et al. Health status of patient with ankylosing spondylitis: a comparison with the general population. Ann Rheum Dis. 2004;63:1605–1610.
    1. Davis J, Revicki D, van der Heijde D, et al. Health-related quality of life outcomes in patients with active ankylosing spondylitis treated with adalimumab: results from a randomized controlled study. Arthritis Rheum. 2007;57:1050–1057.
    1. Feltkamp TE, Mardjuadi A, Huang F, Chou CT. Spondyloarthropathies in eastern Asia. Curr Opin Rheumatol. 2001;13:285–290.
    1. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21:2286–2291.
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381–3390.
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007;146:406–415.
    1. Guignard S, Gossec L, Salliot C, et al. Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis. 2006;65:1631–1634.
    1. Haibel H, Rudwaleit M, Braun J, Sieper J. Six months open label trial of leflunomide in active ankylosing spondylitis. Ann Rheum Dis. 2005;64:124–126.
    1. Haibel H, Rudwaleit M, Brandt HC, et al. Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and magnetic resonance imaging results of a fifty-two-week open-label trial. Arthritis Rheum. 2006a;54:678–681.
    1. Haibel H, Brandt HC, Baraliakos X, et al. Long-term efficacy and safety of adalimumab in the treatment of active ankylosing spondylitis: results of an open-label, 2-year trial. Ann Rheum Dis. 2006b;65:218.
    1. Haibel H, Brandt HC, Song IH, et al. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis. 2007a;66:419–421.
    1. Haibel H, Rudwaleit M, Amtenbrink A, et al. Efficacy of adalimumab in the treatment of preradiographic axial spondylarthritis: results of a 20-week, randomized controlled trial with an open-label extension phase. Ann Rheum Dis. 2007b;66:64.
    1. Haywood KL, Garratt AM, Dziedzic K, Dawes PT. Patient centered assessment of ankylosing spondylitis-specific health related quality of life: evaluation of the Patient Generated Index. J Rheumatol. 2003;30:764–773.
    1. Huang F, Wei JC, Breban M. Thalidomide in ankylosing spondylitis. Clin Exp Rheumatol. 2002;20(Suppl. 28):S158–S161.
    1. Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol. 1994;21:1694–1698.
    1. Kavanaugh A, Tutuncu Z, Catalan-Sanchez T. Update on anti-tumor necrosis factor therapy in the spondyloarthropathies including psoriatic arthritis. Curr Opin Rheumatol. 2006;18:347–353.
    1. Keat A, Barkham N, Bhalla A, et al. BSR guidelines for prescribing TNF-a blockers in adults with ankylosing spondylitis. Report of a working party of the British Society for Rheumatology. Rheumatology (Oxford) 2005;44:939–947.
    1. Khan MA. Update on spondyloarthritis. Ann Intern Med. 2002;136:896–907.
    1. Kirwan J, Edwards A, Huitfeldt B, Thompson P, Currey H. The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years. Br J Rheumatol. 1993;32:729–733.
    1. Lewis SC, Langman MJ, Laporte JR, et al. Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta-analysis based on individual patient data. Br J Clin Pharmacol. 2002;54:320–326.
    1. Maksymowych WP, Jhangri GS, Fitzgerald AA, et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous Pamidronate (60mg versus 10mg) in the treatment of nonsteroidal anti-inflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum. 2002;46:766–773.
    1. Maksymowych WP, Rahman P, Keystone E, et al. Efficacy of adalimumab in active ankylosing spondylitis (AS) – results of the Canadian AS study. Arthritis Rheum. 2005;52:505.
    1. Maksymowych WP, Lambert RGW, Salonen D, et al. Adalimumab reduces spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis (AS)—52 week magnetic resonance imaging (MRI) results from the Canadian AS study. Ann Rheum Dis. 2006;65:65.
    1. NICE (National Institute for Health and Clinical Excellence) National Institute for Health and Clinical Excellence; 2007. Adalimumab, etanercept and infliximab for ankylosing spondylitis: final appraisal determination. Available at: (accessed November 7, 2007).
    1. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis. 2004;63:665–670.
    1. Sieper J, Rudwaleit M, Khan MA, Braun J. Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol. 2006;20:401–417.
    1. Solomon SD, McMurray JJV, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–1080.
    1. van Denderen JC, van der Paardt M, Nurmohamed MT, et al. Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis. Ann Rheum Dis. 2005;64:1761–1764.
    1. van der Heijde D, Dougados M, Davis J, et al. ASsessment in Ankylosing Spondylitis International Working Group/Spondylitis Association of America recommendations for conducting clinical trials in ankylosing spondylitis. Arthritis Rheum. 2005;52:386–394.
    1. van der Heijde D, Luo MP, Wordsworth P, et al. Adalimumab improves physical functioning and work productivity in ankylosing spondylitis (AS) patients: Results from ATLAS. Arthritis Rheum. 2006a;54:99.
    1. van der Heijde D, Kivitz A, Schiff M, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results from a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006b;54:2136–2146.
    1. van der Heijde D, Schiff M, Sieper J, et al. Adalimumab treatment maintains efficacy and safety in patients with ankylosing spondylitis (AS) – 2-year results from ATLAS. Ann Rheum Dis. 2007a;66(Suppl. II):411.
    1. van der Heijde D, Schiff M, Braun J, et al. Adalimumab is effective in reducing signs and symptoms in ankylosing spondylitis patients with total spinal ankylosis – results from ATLAS. Ann Rheum Dis. 2007b;66(Suppl. II):412.
    1. van Tubergen A, Landewé R, van der Heijde D, et al. Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial. Arthritis Rheum. 2001;45:430–438.
    1. Wei JC, Chan TW, Lin H, Huang F, Chou CT. Thalidomide for severe refractory ankylosing spondylitis: a 6-month open-label trial. J Rheumatol. 2003;30:2627–2631.
    1. Zochling J, Braun J. Remission in Ankylosing Spondylitis. Clin Exp Rheumatol. 2006;24(Suppl. 43):S88–S92.
    1. Zochling J, van der Heijde D, Dougados M, et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis. 2006a;65:423–432.
    1. Zochling J, Bohl-Bühler MH, Baraliakos X, Feldtkeller E, Braun J. Nonsteroidal anti-inflammatory drug use in ankylosing spondylitis--a population-based survey. Clin Rheumatol. 2006b;25:794–800.

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