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Therapeutics

Clinical Development in Inflammatory Diseases: Psoriatic Arthritis Psoriatic arthritis (PsA) is a specific form of chronic inflammatory arthritis associated with psoriasis, affecting both men and women equally but with a consistent geographic variability1,2. A systematic review and meta-analysis of 28 studies estimated that the mean global prevalence of psoriatic arthritis is 133 per 100,000 population and the incidence is 83 per 100,000 persons per year. A systematic review and meta-analysis of 266 studies concluded that worldwide, approximately one in four persons with psoriasis has psoriatic arthritis. However, prevalence of psoriatic arthritis internationally ranges widely depending on the population studied3. It was introduced in 1860 by the French physician Pierre Bazin (fr. psoriasis arthritique)4 and in 1964, psoriatic arthritis (PsA) was recognised as a separate disease by the American Rheumatism Association (now the American College of Rheumatology), and is now included as a member of the spondyloarthropathy spectrum. PsA was initially defined by Moll and Wright as ‘an inflammatory arthritis in the presence of psoriasis with a usual absence of rheumatoid factor’5. Early assessment of PsA remains limited and it requires multidisciplinary involvement. The objective of this article is to outline the epidemiology, diagnosis and current clinical development in the treatment of psoriatic arthritis. Background Psoriatic arthritis is a potentially progressive, erosive, chronic, heterogeneous, and systemic inflammatory disease that develops in up to 30% of patients with psoriasis and can manifest in up to six different clinical domains, including peripheral arthritis, dactylitis, enthesitis, psoriasis, psoriatic nail disease, and axial disease6. It is an inflammatory disease in which the cutaneous manifestation of psoriasis coexists with arthritis, usually in the absence of rheumatoid factor4. Etiology of PsA is still unclear but a number of genetic associations have been identified. Inheritance of the disease is multilevel and the role of environmental factors is emphasised and immunology of PsA is complex4. The major histocompatibility complex is a known susceptibility locus for PsA and psoriasis, as shown by the observation that nearly 25% of patients with PsA are positive for human leukocyte antigen (HLA)-B27. Specific HLA alleles are associated with different PsA manifestations. Additionally, there is a strong familial aggregation of PsA with first- and second-degree relatives of affected individuals having increased risk of PsA6. Immunological studies elucidate the interaction between hereditary and environmental factors in the development of psoriasis and PsA. They also explain the contribution of immune factors to the development of inflammatory lesions4. The pathophysiology of PsA is similar to that of psoriasis and involves important cytokines in the interleukin (IL)-23-Th17-IL-17 and tumour necrosis factor (TNF) pathway (e.g. IL-12, IL-17, IL-23, and TNF-a), as well as cytokines such as IL-226. There are stimulating factors (trauma, infection, some medications), resulting in rapid 38 Journal for Clinical Studies

activation of immunocytes, which set up a cascade of cytokines with tumour necrosis factor (secreted by dermal dendritic cells – macrophages) and interferon gamma (IFN-gamma), secreted by activated Th1 cells4. Thus, it is not surprising that many cytokinetargeting biologics and small-molecule inhibitors that provide effective skin clearance in psoriasis also improve joint symptoms and slow radiographic progression in PsA. Clinical Presentation and Diagnosis of PsA Although PsA was thought initially to be a relatively benign disorder, registry data has shown the destructive and progressive nature of the disease; it has a similar impact on quality of life and functional ability as in rheumatoid arthritis. PsA accounts for around 20% of referrals to the early arthritis clinic and presents a significant diagnostic and management challenge. Early diagnosis is important to prevent long-term functional disability and to ensure optimal management of arthritis and key comorbidities5, and management of PsA requires care by a multidisciplinary team including dermatologists, rheumatologists, physiotherapists and orthopaedic surgeons7. Typically PsA involves joints of the axial skeleton with an asymmetrical pattern4 with musculoskeletal involvement, including arthritis, enthesitis, dactylitis and axial involvement as well as potential skin and nail disease. Different patterns of involvement of PsA can mimic different inflammatory arthritides5. In up to 60% of patients, PsA begins with oligoarthritis (≤ 4 joints), but it may affect more joints as the disease progresses (polyarthritis, ≥ 5 joints)7. Peripheral arthritis can cause pain in a variety of joints in PsA and commonly involves the knee (41%), finger (26%), hip (19%), ankle (19%), and wrist (16%). Dactylitis is colloquially referred to as ‘sausage digit,’ and is a distinguishing feature of PsA, characterised by uniform swelling of an entire digit that occurs in up to 48% of patients. Another distinguishing feature of PsA, enthesitis is present in 35% of patients and is defined as inflammation where the tendon, ligament, or joint capsule inserts into bone. Psoriatic lesions can develop on the skin and may affect the nails (e.g. pitting). Axial symptoms, which may occur in up to 50% of patients with PsA, result in back stiffness and pain that improve with movement6. Clinical examination is crucial to diagnose PsA and on examination, joints affected by PsA are usually painful and tender but swelling does not always occur. Moreover, patients often have morning stiffness7.

Table 1 above provides information about the subtypes of PsA7,8 Volume 12 Issue 3

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JCS V12 I3  

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