According to background information in the article, psoriasis, a disease affecting millions of persons worldwide, is a chronic inflammatory disease that has a profound adverse effect on patients' physical, social, and mental well-being. The physical symptoms of psoriasis adversely affect daily functioning, with the most frequently reported symptoms including scaling, itching, and burning. With inadequate control of these symptoms, physical, social, and mental functioning and overall health-related quality of life (HRQL) are compromised. For example, the physical appearance of lesions can cause patients to experience stress and embarrassment and have adverse effects on emotional aspects and normal functioning.
Limitations of currently available psoriasis therapies highlight the need for effective and safe treatment options. Traditional systemic therapies are associated with cumulative toxic effects, potentially increasing the risk of end-organ damage or malignancy.
Kenneth B. Gordon, M.D., of Loyola University Medical Center, Maywood, Ill., and colleagues studied the effect of efalizumab on dermatology-related HRQL in patients with moderate to severe plaque psoriasis (the most common type of psoriasis), using a broad set of outcome measures including physicians' assessments and patients' perceptions.
This phase 3 randomized, double-blind, placebo-controlled trial involved 556 adult patients with stable, moderate to severe plaque psoriasis and was conducted at 30 study centers in the United States and Canada between January and July 2002. Patients were randomly assigned to receive 12 weekly doses of subcutaneous (by injection) efalizumab, 1 mg/kg (n = 369), or placebo equivalent (n = 187).
Patients were considered to have improvement with at least 75 percent improvement on the Psoriasis Area and Severity Index (PASI-75); improvement on the overall Dermatology Life Quality Index (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA) at week 12 vs. baseline.
The researchers found that efalizumab-treated patients experienced significantly greater improvement on all end points than placebo-treated patients. "Twenty-seven percent of efalizumab-treated patients achieved PASI-75 vs. 4 percent of the placebo group. Efalizumab-treated patients exhibited significantly greater mean percentage improvement than placebo-treated patients on the overall DLQI (47 percent vs. 14 percent), Itching VAS (38 percent vs. - 0.2 percent), and PSA frequency and severity subscales (48 percent vs. 18 percent and 47 percent vs. 17 percent, respectively) at the first assessment point," the researchers write. They add that efalizumab was safe and well tolerated, with primarily mild to moderate adverse events.
"Efalizumab treatment reduced the frequency and severity of psoriasis symptoms, particularly in the severity of itching and scaling, the 2 most frequently reported subjective symptoms. The severity and frequency of other symptoms, including bleeding and burning or stinging, also were improved by efalizumab treatment," the authors write. "Efalizumab-treated patients reported greater improvement in their attitudes about their disease, their ability to participate in daily activities (including leisure and work), and their personal relationships, and they reported fewer treatment-related problems compared with placebo."
"Efalizumab was recently approved for treatment of patients with chronic moderate to severe plaque psoriasis. The benefit across physician-assessed end points and multiple patient-reported measures of HRQL observed in this study along with the favorable safety profile suggest that efalizumab could provide a viable treatment option for patients with moderate to severe plaque psoriasis," the authors conclude.
(JAMA. 2003;290:3073-3080. Available post-embargo at jama.com)
Editor's Note: The data presented herein are derived from a clinical trial sponsored by Genentech Inc, which provided the study drug and placebo for this trial. Dr. Gordon has received research funding from Genentech Inc. and co-author Dr. Papp has served as a consultant to Genentech Inc.
EDITORIAL: A PROMISING STEP FORWARD IN PSORIASIS THERAPY
In an accompanying editorial, Robert S. Stern, M.D., of the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, writes that the new treatments including efalizumab represent a promising step in the development of effective and safe treatments for psoriasis.
"Given the lower clinical response rates, higher cost, and unknown long-term risks relative to established therapies, these new agents are best reserved for patients with severe disease unresponsive to, intolerant of, or lacking access to [other therapies]. Only when rigorous, long-term, and competitive efficacy and safety data demonstrate that the new immunomodulating therapies, including efalizumab, are safer than established therapies and at least nearly as effective in long-term use as established systemic therapies should these agents be considered first-line treatments for psoriasis," he writes.
(JAMA. 2003;290:3133-3135. Available post-embargo at jama.com)
Editor's Note: Dr. Stern is the chairman of the Dermatologic and Ophthalmic Drugs Advisory Committee of the U.S. Food and Drug Administration and served on the advisory panel for efalizumab. Dr. Stern served as a consultant to Biogen until summer 2002.
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JAMA