Monday, December 19, 2005

Efficacy of Enbrel (etanercept) as a treatment of psoriasis

Psoriasis has a prevalence of approximately 1500/100,000 (approximately 1 million people have the disease in the US) and affects the skin causing redness and itchiness at multiple sites. The disease can occur in various different forms, the most common of which is plaque psoriasis, a condition associated with raised, red lesions covered with a buildup of dead skin cells. For an in depth look into this disease and its treatments see our recent feature Autoimmune Disorders & Transplant Rejection - Opportunities for the Drug Development Sector,

The non-specificity of early immunomodulators such as cyclosporine and methotrexate, and consequent toxicity has driven the development of various biologic therapies that act to modulate the immune response. The first biologic medication approved by the FDA (January 2003) for the treatment of psoriasis was the T-cell modulator Amevive.

The approval of Amevive was followed by, Enbrel (etanercept), a decoy receptor that blocks tumor necrosis factor-alpha which has now been approved by the FDA for the treatment of psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis and ankylosing spondylitis. Even more recently Raptiva (infliximab; October 2003) was approved for the treatment of psoriasis. This monoclonal antibody neutralizes anti-TNF. About 30% of psoriasis patients suffer psoriatic arthritis, and Remicade and Humira, originally treatments of rheumatoid arthritis, have both recently been approved for the treatment of this condition. Like Raptiva, Remicade and Humira are both antibodies that neutralize anti-TNF

Overall psoriasis has greatly benefited from the advent of the TNF blockers Once a disease associated often uncontrollable burning sensation and disfiguration of the skin and frequently accompanied by loss of mobility and joint pain biologics have transformed psoriasis. The biologics can greatly improve skin lesions and reduce joint disease severity as measured by physician-reported clinical outcomes. Equally important is the patient perspective on the effect of etanercept therapy on daily life.

In their Br J Dermatol paper published this month (Dec;153(6):1192-9) and featured on the Dec 19th edition of DailyUpdates, Krueger et al assess patient-reported outcomes in patients with psoriasis receiving etanercept therapy. In this multinational, randomized, phase III trial, patients with psoriasis received placebo, etanercept 50 mg per week or etanercept 50 mg twice weekly during the initial 12-week, double-blind period. Thereafter, all patients received open-label etanercept (50 mg per week).

The study evaluated the effects of treatment on the Dermatology Life Quality Index (DLQI), Short Form-36 Health Survey (SF-36), patient rating of pruritus, and patient global assessment of psoriasis.

At week 12, DLQI total score improved by 65-70% in patients receiving etanercept compared with 6% in patients receiving placebo. Improvements were reported across multiple components of DLQI and SF-36 establishing that the efficacy of treatment was not biased towards a few aspects of the disease. Moreover, patients rated disease severity as improving from moderate/severe to minimal/good.

Based on this study, etanercept is concluded not only to improve disease activity as indicated by clinical outcomes but also by patient experiences.

Despite the efficacy of TNF blockers, two large patient surveys, one conducted by the National Psoriasis Foundation (NPF) and the other by the European Union Federation of Psoriasis Associations, have reveal that patients are dissatisfied with currently available therapeutic options. Despite the availability of new biologics, the NPF survey revealed that only 18% of survey respondents with severe psoriasis were currently receiving systemic therapy; 32% of patients indicated that their psoriasis therapy was not aggressive enough and this is partly due to the prescribing patterns of dermatologists who generally approach psoriasis in a stepwise fashion starting with conservative treatments and progressing towards biologics. This approach is becoming obsolete as the safety and efficacy of biologics is becoming established and patients with severe psoriasis should now be evaluated as candidates for first line biologic therapy.

One short-fall in the treatment of psoriasis is the lack of head-to-head studies comparing the efficacy or tolerability of the 5 approved biologic psoriasis treatments. This is important considering the expense of therapies and the need to direct the best possible treatment to patients on an individual basis. Hopefully such studies will eventually be conducted and when this occurs data should include patient-reported outcomes as described in the featured journal article.


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