Cytokine blockers in psoriatic arthritis.

Abstract

The cellular events underlying the pathogenesis of psoriatic arthritis (PsA) and psoriasis have not yet been fully elucidated. Nevertheless, some clues to these conditions are beginning to emerge. In particular, a growing body of data supports the role of proinflammatory cytokines, such as tumour necrosis factor (TNF), in the pathophysiology of PsA and psoriasis. Raised levels of these cytokines are found in the joints of patients with PsA, as well as in psoriatic skin lesions. Physiotherapy, non-steroidal anti-inflammatory agents, corticosteroids, and disease modifying antirheumatic agents, such as methotrexate, are the most commonly used treatments for PsA. However, the data supporting the effectiveness of these treatments are limited, and disease resolution is usually incomplete. This study examined the effects of etanercept, a TNF inhibitor, in patients with PsA. Etanercept treatment was well tolerated and resulted in significant improvement in the signs and symptoms of PsA and in psoriatic skin lesions. Infliximab, another TNF inhibitor, has also been shown to be effective in patients with PsA. Such studies confirm the importance of proinflammatory cytokines in PsA, and hold out hope for patients who require new options for the treatment of their disease.

(Ann Rheum Dis 2001;60:iii37-iii40)

Psoriatic arthritis (PsA) is a complication of psoriasis, a skin disorder. Psoriasis is present in 1-3% of the general population, (1 2) and approximately 5-30% of patients with psoriasis develop PsA. (1 3-5) Patients with PsA may develop considerable joint damage or even deformity. (6) The cause and pathogenesis of PsA are not yet understood, but disease progression appears to be associated with inflammation early in the course of the disease. (7) PsA is often treated in the same manner and with the same agents as are used for rheumatoid arthritis (RA), but there is no evidence that these drugs prevent disease progression, and the adequacy and safety of these treatments have also been called into question in this patient group. (8)

Several studies have shown that proinflammatory cytokines, including tumour necrosis factor (TNF), are raised in the skin lesions and serum of patients with psoriasis (9) and in the synovial fluid and synovium of patients who additionally have PsA. (9-12) These findings provide a rationale for the use of TNF blockers in the treatment of these diseases. Recent studies have shown that TNF inhibitors relieve the signs and symptoms of PsA. (13 14) These findings, and their implications for the treatment of PsA, are discussed here.

Background

PsA typically strikes patients between 30 and 55 years of age. Approximately 50% of patients with PsA are male. (3) The presentation of a patient with PsA can be quite variable, involving any number of joints in an asymmetrical or symmetrical pattern. Specific areas may be affected, such as the distal interphalangeal joints or the spine, or the arthritis may be widespread. Polyarthritis in PsA may be similar to RA and is asymmetrical in about half of the cases. (8) Most patients (about 75%) develop the skin lesions of …