Millions upon millions of men, women and children suffer from moderate to severe psoriasis the world over.
Essentially a skin disease marked by itching and scaling, psoriasis actually bedevils its victims with a lifetime of social, emotional and bodily anguish, with only on-and-off relief administered by a clutch of experimental antibodies, plus more extreme agents such as methotrexate - a potent cancer drug. The physical appearance of the psoriatic lesions can cause patients to experience exquisite stress and embarrassment with adverse effects on emotional aspects and normal functioning. More scientifically, patchwork, or plaque, psoriasis is a common multifactorial inherited condition, characterized by the eruption of discrete and conjoined reddish, silvery-scaled marcropapules. The lesions pop up mainly on elbows, knees, scalp and trunk, where the symptoms might typically hang on for more than 30 years.
Up to 10 percent of psoriasis patients, especially younger ones, harbor suicidal thoughts, compared with some 3 percent of general medical patients, indicating a significant unmet medical need.
A five-syllable, scarcely pronounceable chemical remedy - parsed as e-fal-zum-ab - is promising. It is a humanized monoclonal immunoglobulin G1 antibody that targets T-cell interactions central to the physiology of psoriasis. It's manufactured by Genentech Inc., of South San Francisco, under the trade name Raptiva. A Phase III randomized, double-blind, placebo-controlled trial of the drug enrolled 556 adult patients with stable plaque psoriasis. It was conducted at 30 study centers in the U.S. and Canada between January 2002 and July 2002. Three hundred and sixty-nine patients were randomly assigned to receive 12 weekly subcutaneous injections of efalizumab; 187 received placebo. The results were measured by both physician and patient assessment.
The results were reported in The Lancet, dated Dec. 16, 2003, then shifted to the Journal of the American Medical Association (JAMA), reprinted on Dec. 17, 2003. Its definitive title is "Efalizumab for patients with moderate to severe plaque psoriasis: A randomized controlled trial." Its corresponding author is dermatologist Kenneth Gordon at Loyola University Medical Center in Maywood, Ill. The eight-page JAMA article is trailed by a three-page editorial titled "A promising step forward in psoriasis therapy," authored by dermatologist Robert Stern at the Harvard-affiliated Beth Israel Deaconess Medical Center in Boston.
"This and other studies," Stern observed, "demonstrate that efalizumab is superior to placebo. To determine the place of this novel drug in the current armamentarium, however, its safety and efficacy must be determined relative to other therapies for severe psoriasis. To accomplish this, it is important to assess how the results, as presented, translate into clinical meaningful changes in health status. Changes in PASI [Psoriasis Area and Severity Index] score can reflect very different objectives and subjective disease status. Although the PASI score is accepted by the U.S. FDA," Stern pointed out, "the agency and its consultants have emphasized the shortcomings of this measure.
"Although available treatment options for psoriasis patients have changed little over nearly 20 years," Stern's editorial leads off, "the disease has recently become a focus for innovative therapies. With the development of monoclonal antibodies that alter immune function, efalizumab-related products have demonstrated beneficial effects.
"Limitations of currently available psoriasis therapies," the editorial goes on, "highlight the need for new, effective and safe treatment options. The above-cited traditional systemic therapies carry cumulative toxic consequences, which potentially increase the risk of end-organ damage or malignancy.
"In the treatment of psoriasis," the editorial continued, "several criteria contribute to the notion of efficacy. Patients' expectations for improvement from low-risk topical therapies vs. higher cost and higher-risk systemic treatment are likely to be different. Patients who undertake a therapy that is inconvenient, costly or invasive are disappointed if the treatment does not clear their skin.
"Costing more than $10,000 per year, the new biologies are far less affordable than the traditionals [PUVA, methotrexate, etc.]. Among patients with psoriasis responding to 24 weeks of efalizumab, two-thirds experienced relapse within 12 weeks of discontinuing therapy. This suggests that continuous drug is required to maintain benefit."