Biologicals in Ankylosing Spondylitis: Current Concepts

Govt Hospital Vijay Pur, J&K Health Services, Jammu, India.

Abstract

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. Anti-TNF (tumour necrosis factor)-α agents have been found very effective for the treatment of both peripheral and axial symptoms in patients with AS. Etanercept, infliximab and adalimumab are approved by Food and Drug Administration (FDA) for AS. Systemic Lupus Erythematosus syndrome, demylinating diseases, neurodegenerative diseases, pancytopenia, severe infections, cardiovascular diseases etc. are some of the important side-effects reported with TNF-α blockers. TNF-α plays an important role in the host defense against mycobacterial infection, particularly in granuloma formation and inhibition of mycobacterial dissemination. There are recent reports of reactivation of tuberculosis after anti-TNF therapy. FDA recommended a black box for tuberculosis on the product labeling of infliximab. It is highly recommended to consider prophylactic anti- tubercular therapy (with isoniazid or isoniazid and rifampicin combination) before starting anti- TNFα therapy in patients with evidence of past history of tuberculosis or abnormal chest x-ray suggesting tuberculosis. However, extensive post-marketing surveillance is necessary to re-evaluate the risk-benefit ratio of these biologic therapies.

Etanercept, infliximab, adalimumab, ankylosing spondylitis

Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness and discomfort AS affects about 0.5%–1.0% of the population (1). Prevalence estimates vary between 0.1% and 2% in different populations with male:female ratio of around 5:1 and the peak age of onset is at 15-35 years (2). Recently, there have been 2 major developments in the management of AS : use of magnetic resonance imaging to visualize the inflammatory changes in the sacroiliac joint and the axial spine and the demonstration that TNF (tumor necrosis factor) blocking agents are highly efficacious in reducing spinal inflammation and slowing radiographic progression (3). Treatment for AS focuses on relieving pain and stiffness, reducing inflammation, keeping the condition from getting worse and enabling patient to continue daily activities (4). Early diagnosis and treatment may reduce pain, stiffness, inflammation and deformity.

Drug Treatment for AS
Initial treatment for AS may include patient education regarding nature of the disease and ways to control complications, physiotherapy, non-steroidal antiinflammatory drugs (NSAIDs), assistive devices like canes or walkers and alternative therapies like yoga or acupuncture (4),(5). Several NSAIDs are available, but phenylbutazone is considered the NSAID of choice in AS (1). However, all NSAIDs share common gastrointestinal toxicity and they should be administered during periods of flare-up of the disease (6) However, additional, stronger medications like corticosteroids and Disease-modifying antirheumatic drugs (DMARDs) may be needed for some parients. The DMARD most often studied and prescribed for AS is combination of 5 amino salicyclic acid and sulfapyridine (4). DMARDs are required in cases of longstanding severe or refractory AS. Drugs like methotrexate or gold salts require properly designed controlled studies to evaluate their effectiveness in the treatment of AS, while immunosuppressive agents have little to offer in the management of patients with AS and require further studies (1). Enthesopathy may be treated with local injection of corticosteroids; sacroiliac joint pain may be managed by corticosteroid injection performed under fluoroscopic control or guided by computed tomography (1). Recent evidences showed efficacy of pamidronate as antiinflammatory agent in AS (7),(8). However, in ankylosing spondylitis there is an unmet medical need, since there are almost no DMARDs available for severely affected patients, especially those with spinal manifestations (7). Anti-TNF-α agents have been found very effective for the treatment of both peripheral and axial symptoms in patients with AS (9),(10).

Biological agents in AS
TNF-α is a potent cytokine produced by the body and is involved in normal inflammatory and immune responses (11). It also induces other cytokines like IL(interleukin)-1, IL-6, IL-8, platelet derived growth factor-B, ecosanoids, platelet activating factors and granulocyte monocyte colony stimulating factor (11). Anti TNF-α therapy down-regulates the monocyte capacity to produce proinflammatory cytokines and induces a shift to produce more anti-inflammatory cytokine (11). Etanercept (July 2003), infliximab (December 2004) and adalimumab are approved by FDA (Food and Drug Administration) for AS (