Understanding the role of tumor necrosis factor inhibition in ankylosing spondylitis

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disorder that affects approximately 350,000 patients in the United States. Over time, the spinal and peripheral joint involvement of AS may cause severe disability and functional limitations. Research in the molecular and cellular events of AS has uncovered a distinct role for the proinflammatory cytokine, tumor necrosis factor (TNF), in the pathogenesis of this disease. OBJECTIVES: This article reviews the role of TNF in the pathogenesis of AS and evaluates new therapeutic options for the disease. METHODS: Literature searches were conducted and various studies were reviewed and evaluated from the perspective of study design and validity of conclusions. Data are presented from animal studies and human clinical trials designed to test the efficacy of TNF inhibition in AS. RESULTS: The TNF inhibitors etanercept and infliximab not only demonstrate a significant reduction in the signs and symptoms of AS but also improve quality of life while reducing serious toxicities. Etanercept is the first TNF inhibitor to be approved by the United States Food and Drug Administration (FDA) for use in the treatment of AS and has recently been approved in the European Union. Infliximab has also been approved for use in the European Union. CONCLUSIONS: Early treatment with TNF inhibitors in patients with RA has been shown to result in significant improvements in disability, pain, and joint scores compared with delayed treatment. Ongoing trials are currently investigating whether these agents can halt or delay disease progression in patients with AS. RELEVANCE: Understanding the role of TNF inhibition in AS has led to new therapies that offer improved function and less disability for many patients suffering from this disease.