Drug Profile
Expert Review of Clinical Pharmacology Downloaded from informahealthcare.com by University of Queensland on 03/13/15 For personal use only.
Ustekinumab for the treatment of psoriatic arthritis Expert Rev. Clin. Pharmacol. 7(2), 111–121 (2014)
David John Chandler*1 and Anthony Bewley2 1 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK 2 Royal London Hospital, Whitechapel, London, E1 1BB, UK *Author for correspondence: [email protected]
Psoriatic arthritis occurs commonly in those with psoriasis and is associated with progressive joint destruction, physical disability, reduced quality of life and increased mortality. For many patients the currently available treatment options including the anti-TNF treatments are inadequate. Recent data suggest that ustekinumab can provide an effective treatment option in these patients. We discuss the role of ustekinumab in the treatment of psoriatic arthritis and highlight areas requiring further work. KEYWORDS: biologics • cutaneous immunology • IL-12 • IL-23 • psoriasis • psoriatic arthritis • ustekinumab
In this article, we will review the role of ustekinumab in the treatment of psoriatic arthritis (PsA). We will discuss other currently available treatments including both established treatments and novel therapeutic approaches. Psoriasis is a multisystem disease
Psoriasis is a chronic immune-mediated inflammatory skin disease affecting 1.3–2.2% of the UK population [1]. Psoriasis can affect multiple organ systems and is associated with a number of medical comorbidities including cardiovascular disease, metabolic syndrome, nonalcoholic fatty liver disease, diabetes mellitus and depression [2–5]. Recent evidence supports a possible relationship between the severity of psoriasis and cardiovascular risk. The risks of myocardial infarction and stroke are significantly increased in mild and severe psoriasis; however, cardiovascular mortality is significantly increased only in severe psoriasis [6,7]. Psoriatic arthropathy
PsA is an inflammatory seronegative spondyloarthropathy that occurs in 6–42% of patients with psoriasis [8]. PsA affects men and women equally and occurs most commonly between the ages of 36 and 40 years [9]. The majority of patients develop skin disease prior to the onset of joint disease, thus dermatologists are well placed to detect and treat PsA early in the course of disease. In the EDUCATE trial, 84% of patients with PsA developed cutaneous informahealthcare.com
10.1586/17512433.2014.888310
manifestations, an average of 12 years before the onset of joint disease [10]. Clinical features
The diagnosis of PsA is clinical based on the pattern of joint inflammation and the presence of extra-articular manifestations including skin lesions and nail changes. Radiographic changes can be helpful and rheumatoid factor is absent in the majority of patients. PsA can affect both peripheral joints and the axial skeleton. Approximately 95% of patients with PsA have peripheral joint disease, often involving multiple joints [8,11]. Up to half of the patients have both peripheral joint and axial disease, and very few patients have disease exclusively involving the spine. Symptoms vary in severity and include pain, stiffness, swelling and tenderness of the affected joints and surrounding structures. Distal interphalangeal joint involvement, dactylitis and enthesitis are characteristic of PsA. Dactylitis commonly affects the feet in an asymmetric distribution and is associated with greater radiological damage compared with digits not affected by dactylitis [12]. Moll and Wright provided the first diagnostic criteria for PsA and described five clinical patterns of disease [13]. These included distal interphalangeal joint disease pattern, oligoarticular pattern (
Expert Review of Clinical Pharmacology Downloaded from informahealthcare.com by University of Queensland on 03/13/15 For personal use only.
Ustekinumab for the treatment of psoriatic arthritis Expert Rev. Clin. Pharmacol. 7(2), 111–121 (2014)
David John Chandler*1 and Anthony Bewley2 1 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK 2 Royal London Hospital, Whitechapel, London, E1 1BB, UK *Author for correspondence: [email protected]
Psoriatic arthritis occurs commonly in those with psoriasis and is associated with progressive joint destruction, physical disability, reduced quality of life and increased mortality. For many patients the currently available treatment options including the anti-TNF treatments are inadequate. Recent data suggest that ustekinumab can provide an effective treatment option in these patients. We discuss the role of ustekinumab in the treatment of psoriatic arthritis and highlight areas requiring further work. KEYWORDS: biologics • cutaneous immunology • IL-12 • IL-23 • psoriasis • psoriatic arthritis • ustekinumab
In this article, we will review the role of ustekinumab in the treatment of psoriatic arthritis (PsA). We will discuss other currently available treatments including both established treatments and novel therapeutic approaches. Psoriasis is a multisystem disease
Psoriasis is a chronic immune-mediated inflammatory skin disease affecting 1.3–2.2% of the UK population [1]. Psoriasis can affect multiple organ systems and is associated with a number of medical comorbidities including cardiovascular disease, metabolic syndrome, nonalcoholic fatty liver disease, diabetes mellitus and depression [2–5]. Recent evidence supports a possible relationship between the severity of psoriasis and cardiovascular risk. The risks of myocardial infarction and stroke are significantly increased in mild and severe psoriasis; however, cardiovascular mortality is significantly increased only in severe psoriasis [6,7]. Psoriatic arthropathy
PsA is an inflammatory seronegative spondyloarthropathy that occurs in 6–42% of patients with psoriasis [8]. PsA affects men and women equally and occurs most commonly between the ages of 36 and 40 years [9]. The majority of patients develop skin disease prior to the onset of joint disease, thus dermatologists are well placed to detect and treat PsA early in the course of disease. In the EDUCATE trial, 84% of patients with PsA developed cutaneous informahealthcare.com
10.1586/17512433.2014.888310
manifestations, an average of 12 years before the onset of joint disease [10]. Clinical features
The diagnosis of PsA is clinical based on the pattern of joint inflammation and the presence of extra-articular manifestations including skin lesions and nail changes. Radiographic changes can be helpful and rheumatoid factor is absent in the majority of patients. PsA can affect both peripheral joints and the axial skeleton. Approximately 95% of patients with PsA have peripheral joint disease, often involving multiple joints [8,11]. Up to half of the patients have both peripheral joint and axial disease, and very few patients have disease exclusively involving the spine. Symptoms vary in severity and include pain, stiffness, swelling and tenderness of the affected joints and surrounding structures. Distal interphalangeal joint involvement, dactylitis and enthesitis are characteristic of PsA. Dactylitis commonly affects the feet in an asymmetric distribution and is associated with greater radiological damage compared with digits not affected by dactylitis [12]. Moll and Wright provided the first diagnostic criteria for PsA and described five clinical patterns of disease [13]. These included distal interphalangeal joint disease pattern, oligoarticular pattern (
