Impact of efalizumab on psoriasis-specific patient-reported outcomes: results from three randomized, placebo-controlled clinical trials of moderate to severe plaque psoriasis

Journal of Drugs in Dermatology, Jan-Feb, 2004 by Alan Menter, Mark Kosinski, Brian W. Bresnahan, Kim A. Papp, John E. Ware

Abstract

The objective of this study was to document the disease burden associated with moderate to severe plaque psoriasis, and assess the impact of efalizumab psoriasis treatment in improving patient-reported outcomes. This included analysis of patient-reported dermatology-related quality of life (DRQL) and psoriasis symptom scores among patients with moderate to severe psoriasis participating in three phase III, randomized, double-blinded, parallel-group, placebo-controlled, multi-center clinical trials conducted to evaluate the efficacy and safety of efalizumab.

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A total of 1,242 patients with moderate to severe psoriasis treated either with efalizumab 1.0 mg/kg/wk or placebo were followed for 12 weeks. DRQL and psoriasis symptom severity were assessed at baseline (pre-treatment) and at the end of the first treatment phase (12 weeks). DRQL was measured using the Dermatology Life Quality Index (DLQI). Symptoms were measured using the Psoriasis Symptom Assessment (PSA) and an Itch scale. Disease burden was assessed at baseline by examining responses to individual questions of the DLQI, PSA, and Itch patient-reported outcome measures. The impact of treatment on disease burden was assessed over a 12-week double-blind study period by comparing changes in DLQI, PSA, and Itch scale scores between the active treatment and placebo groups. Patient-reported outcomes were also assessed during a 12-week extended treatment phase.

Prior to treatment, the responses to DLQI and PSA items revealed significant disease burden. Greater than 90% of patients reported being embarrassed or self conscious because of their skin, 53% reported that their skin prevented them from working or studying, and 98% reported that scaling and itching was bothersome. Compared to placebo-treated patients, efalizumab-treated patients showed significant improvement in patient-reported outcomes, reducing the limitations and burden associated with moderate to severe psoriasis within each of the three studies, as measured by DLQI (p<0.001), PSA-Severity (p<0.001), PSA-Frequency (p<0.001), and Itch (p<0.001) scores. Across all measures, the proportion of patients that improved on both statistical and clinical criteria for meaningful improvement was at least twofold greater among efalizumab-treated patients than in placebo-treated patients. The benefit of efalizumab was maintained over the course of an additional 12 weeks during an extended treatment phase.

In conclusion, patients with moderate to severe plaque psoriasis reported significant DRQL burden and symptom severity at baseline, but efalizumab significantly improved patient-reported DRQL and reduced the frequency and severity of psoriasis symptoms during 12-week double-blind and 12-week extended treatment periods.

Introduction

Psoriasis is one of the most common chronic skin diseases affecting approximately 2% of the general US population (1) with an annual incidence of between 150,000 and 260,000 new cases (2). Individuals with psoriasis experience reduced quality of life (3-6), significant psychosocial distress (7-10), and disability (11,12). Evidence also shows that the impact of psoriasis on dermatology-related quality of life (DRQL) is more pronounced in patients with more severe disease (13,14). In a recent study the impact of psoriasis on patient's physical functioning and mental health has been shown to rival or exceed that of other diseases with well understood morbidity like diabetes, heart disease, cancer and arthritis (15).

In a large survey conducted by the National Psoriasis Foundation, nearly one half of the respondents reported being frustrated with the ineffectiveness of current therapies available for treating psoriasis (16). Many factors may contribute to the difficulties in treating psoriasis effectively. First, despite the documented impact of psoriasis on patients' lives, skin diseases in general are often considered to have less impact on patient functioning and well-being than chronic diseases affecting other body systems (17). Second, the evaluation of treatment efficacy with measurements that focus only on the clinical severity of psoriasis do not accurately gauge its effects on patient's lives (18,19); consequently, the impact of psoriasis on the patient is often underestimated. Third, topical agents typically used to treat mild to moderate psoriasis, while effective in the short-term, can be burdensome, messy, and difficult to use--characteristics that may substantially reduce patient adherence and satisfaction with treatment even if the agent is effective. For various reasons, topical agents are all too frequently prescribed as monotherapy for patients with more extensive disease. Fourth, treatment of moderate to severe forms of psoriasis generally involves use of traditional systemic therapies, such as methotrexate, cyclosporine, or ultraviolet light therapy, such as PUVA or UVB. These agents, like corticosteroids, may be very effective in the short-term, but carry with them concerns about risks associated with long-term exposure (20). Thus psoriasis, a life-long disease, is usually treated with intermittent therapies on a rotational basis, producing patient frustration and frequent withdrawal from maintenance therapy (16).