Traditional Therapies in the Management of Moderate to Severe Chronic Plaque Psoriasis: An Assessment of the Benefits and Risks

L. Naldi; C.E.M. Griffiths

Disclosures

The British Journal of Dermatology. 2005;152(4):597-615. 

In This Article

Summary and Introduction

Psoriasis is a chronic, recurrent disease that affects between 1% and 3% of the population. Patients with moderate to severe disease generally require phototherapy (e.g. narrowband ultraviolet B radiation), photochemotherapy (oral psoralen plus ultraviolet A radiation) or systemic agents (e.g. ciclosporin, methotrexate, oral retinoids, fumaric acid esters) to control their disease adequately. In general, these therapeutic modalities have proven to be highly effective in the treatment of psoriasis. However, potentially serious toxicities can limit their long-term use. Given that there is no standard therapeutic approach for patients with moderate to severe psoriasis, the benefits and risks of phototherapy, photochemotherapy and systemic therapy must be weighed carefully for each patient, and treatment individualized accordingly. This review summarizes the benefits and risks of traditional, nonbiological therapies for moderate to severe chronic plaque psoriasis.

Psoriasis is a chronic, recurrent disease of variable severity that affects between 1% and 3% of the population.[1] The severity of psoriasis traditionally has been evaluated by objective measurement of the extent of the body surface affected and consideration of the subtype of psoriasis, degree of disability, and feasibility of topical therapy.[2] More recently, it has become apparent that clinical measures of severity do not necessarily reflect the potentially serious impacts of psoriasis on patients' quality of life.[3,4,5,6] Little is known about the long-term burden of the disease.

Although topical preparations may be sufficient to control psoriasis symptoms in patients with relatively mild disease, patients with moderate to severe disease usually require phototherapy or systemic agents to achieve good clearance. In general, these more aggressive therapies have proven to be highly effective in the treatment of psoriasis. However, potentially serious toxicities associated with phototherapy and each of the traditional systemic agents can limit their long-term use and may necessitate rotation of therapies and/or treatment regimens. Because the rotational approach may incorporate periods off treatment, psoriasis symptoms can return, often without warning.[7,8]

Therapies currently approved in various countries across Europe for the treatment of moderate to severe psoriasis include narrowband ultraviolet (UV) B (NBUVB) radiation, photochemotherapy [oral psoralen plus UVA radiation (PUVA)], ciclosporin, methotrexate and oral retinoid therapy ( Table 1 ). Other systemic therapies, such as hydroxyurea or fumaric acid esters (FAEs), are approved in a very small number of European countries or may be used off-label for the treatment of psoriasis. Not all of these therapies are approved across the European Union; furthermore, both labelling indication and dosing regimen vary across all countries. Treatment of moderate to severe psoriasis is often initiated with NBUVB and/or broadband UVB (BBUVB) followed by PUVA. Combination and rotation of several treatments (topical, phototherapy and systemic) is common, although empirical. In some countries (Austria, Denmark, Netherlands, Portugal) methotrexate is often prescribed only as a last resort; however, in other countries (Belgium, Luxembourg, France, U.K.) methotrexate is used as a first-line systemic treatment for severe psoriasis. In Germany, Italy, France and many other countries, methotrexate is used if concomitant acute psoriatic arthritis is observed. In Italy, where ciclosporin is the most commonly used systemic therapy for psoriasis, methotrexate is usually reserved for treatment of patients resistant to classical therapies. Physicians in some countries (France, U.K.) combine ciclosporin with methotrexate. Retinoids seem to be the last choice in several European countries and are usually used in combination, as monotherapy appears to have suboptimal efficacy for chronic plaque psoriasis.

As there is no standard therapeutic approach for patients with moderate to severe psoriasis, the benefits and risks of phototherapy or systemic therapy must be weighed carefully for each patient, and treatment individualized accordingly. Considering that psoriasis is a lifelong disease, the patient's lifetime cumulative exposure to these agents must be taken into consideration. Also, the impacts of regular and sometimes invasive monitoring of treatment-related toxicity may influence treatment decisions.

Accurate comparison of the efficacy of therapies for moderate to severe psoriasis is limited by the scarcity of comparative clinical trials. A European survey of psoriasis clinical trials published between 1977 and 2000 found that only six of 75 (8%) randomized trials of systemic therapy were comparative studies of treatments from different therapeutic classes, and only two trials compared two or more systemic therapies (ciclosporin vs. etretinate in both trials).[1,9,10] Griffiths et al . identified no further comparative trials of single-agent systemic therapies in their systematic review of randomized clinical trials for severe psoriasis.[11] The interpretation of clinical efficacy data is further limited by several factors, including small patient numbers, short study duration, heterogeneity of data, inconsistent dosage and duration of treatment, and inadequate documentation of outcome measures.[1,11,12]

Despite these limitations in the literature, there is considerable clinical experience supporting the efficacy of phototherapy and systemic therapy for psoriasis. This review briefly summarizes the efficacy of traditional therapies for psoriasis, focusing on data from randomized placebo-controlled clinical trials where available. Safety concerns associated with each treatment are also described. The objective of this review is to assess the benefits and risks of traditional therapies for moderate to severe chronic plaque psoriasis.

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