Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 2010, 9, 35-40 35 1871-5230/10 $55.00+.00 © 2010 Bentham Science Publishers Ltd. Treatment of Ankylosing Spondylitis with Biologic Agents Mehmet Tuncay Duruöz* Celal Bayar University Medical School, Physical Medicine and Rehabilitation Department, Rheumatology Division, Manisa, Turkey Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disorder of the spine that can lead to significant disabil- ity if left untreated. Although conventional treatments can be successful in alleviating symptoms, they have not been shown to stop progression of the disease. The proinflammatory cytokine tumor necrosis factor (TNF) is central to the pathogenesis of AS. Several TNF- blocker drugs such as infliximab, adalimumab, etanercept and golimumab have been developed and shown to control symptoms effectively, possibly preventing both clinical and radiographic progression of the disease in patients with AS. Acute inflammatory lesions in the spine and sacroiliac joints can be effectively suppressed by the TNF- blockers in AS, suggesting that bone destruction and bone proliferation might be prevented. Keywords: Ankylosing spodylitis, biologic agents, TNF blockers, treatment. INTRODUCTION Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis, spinal inflammation and progressive spinal fusion with a prevalence between 0.5% and 1.0%. It starts early in life, before the age of 30 years in about 80% of patients [1, 2]. Peripheral joint and nonarticular involvements may also occur in AS and the severity of symptoms and prognosis show variations from patient to patient. Untreated AS is as- sociated with increased morbidity and mortality. The signifi- cance of TNF- in the pathogenesis of AS has been eluci- dated by a phenotype in the transgenic mouse model where overexpression of that cytokine resulted from a deletion in the 3' regulatory region of the TNF- transgene [3]. Overex- pressed TNF- is associated with sacroiliitis, cartilage dam- age and bone erosions and animals given infliximab have shown substantial decreases in those findings [4]. In human studies, intense mononuclear infiltrations and staining of TNF- messenger RNA (mRNA) have been described in both sacroiliac joints and entheses [5, 6]. While effective treatment for active and severe AS has been limited previously, treatment outcomes achieved in the recent years with biologic agents that directly target and block TNF- are promising. TNF- is expressed in high amounts at the site of inflammation in AS, which provided the basis to initiate treatment studies with TNF- blocking agents [7]. TNF- blocking therapies have revolutionised the treatment of ankylosing spondylitis. Treatment of active AS with TNF blockade appears to be associated with improved capacity for work [8]. The first biologic therapy that has been reported to be beneficial in AS treatment is infliximab, a chimeric mono- clonal IgG 1 . It was followed by etanercept which is a recom- *Address correspondence to this author at the CBU Medical School, PMR Department, Rheumatology Division, Manisa, Turkey; Tel: +90-533- 5121548; Fax: +90-232-3755044; E-mail: tuncayduruoz@gmail.com binant 75 kiloDalton (kDa) TNF receptor Immunglobulin 1 (IgG 1 ) fusion protein. Third and forth TNF- blockers, adalimumab and golimumab are human anti-tumor necrosis factor (TNF) monoclonal antibodies that act principally by targeting and neutralizing TNF to prevent inflammation. There is no evidence that one TNF blocking agent is more effective than any other for the treatment of musculoskeletal manifestations of AS [9-13]. The only other non-TNF biological therapy is the inter- leukin-1 inhibitor anakinra tested in open-label trials. In one study, there was significant improvement in pain (p=0.04) and function (p=0.02) [14] with anakinra, while another study failed to show any significant improvement with that treatment [15]. The ASAS group has published a comprehensive, evi- dence-based consensus statement for initiation of TNF- blocking treatment in AS [16,17]. According to ASAS/ EULAR (Assessment of Spondyloarthritis International So- ciety / Eurpean League Against Rheumatism) guidelines for the management of ankylosing spondylitis (AS), anti-tumour necrosis factor (TNF) treatment should be given to patients with persistently high disease activity despite receiving con- ventional treatments recommended by the ASAS guidelines [18]. There is no evidence to support the mandatory use of disease modifying antirheumatic drugs (DMARD) before, or concomitant with TNF- blocking treatment in patients with axial disease. The onset of clinical action with TNF-  block- ers is rapid, and therapeutic effect persists for up to 3 years with continued treatment [19, 20]. Cessation of treatment results in a high proportion of patients with clinical relapse. Although adding methotrexate to infliximab treatment in rheumatoid arthritis improves clinical outcome [21] and re- duces side effects [22], there has been no evidence to support any additional benefit with concomitant methotrexate use in AS [23]. Several studies have demonstrated that active inflamma- tion of the sacroiliac joints or spine is significantly reduced by all three TNF blocking agents, as shown by magnetic