Psoriatic arthritis: recent progress in pathophysiology and drug development

Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy, afterrheumatoid arthritis diagnosis, in early arthritis clinics. Most patients haveestablished psoriasis, often for years, prior to the onset of joint pain andswelling; in addition, associated features of nail disease, dactylitis, enthesitis,spondylitis or uveitis may be present. Psoriasis may not be immediately apparent, assmall or patchy lesions may occur in the scalp or perineum. PsA presents as asymmetrical polyarthritis, similar to rheumatoid arthritis, or an asymmetricaloligoarthritis with a predilection for the distal interphalangeal joints. Spinalinvolvement is similar, although not identical, to ankylosing spondylitis. Jointdamage occurs early; up to 50% of PsA patients have an 11% annual erosion rate in thefirst 2 years of disease duration, suggesting it is not a benign condition.There have been significant advances in our understanding of PsA pathogenesis inrecent years, in the areas of genetics and molecular biology, implicating both theinnate and the adaptive immune systems. This has lead to the introduction ofevidence-based targeted therapy, primarily with tumour necrosis factor inhibitor(TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such asmethotrexate and leflunomide, remains the first-choice therapeutic intervention, eventhough there are few randomised controlled trials with these agents. In contrast, anumber of successful studies of TNFi agents demonstrate excellent efficacy, incombination with methotrexate, and several novel agents are currently in developmentfor the treatment of PsA.