Mark Lebwohl, MD
from WebMD Scientific American® Medicine
Several drugs are poised for FDA approval for the treatment of psoriasis. Two medications, etanercept (Enbrel) and infliximab (Remicade), are already used to treat rheumatoid arthritis and Crohn disease; a third agent, alefacept (Amevive), has been recommended for approval; another medication, efalizumab (Raptiva), has undergone extensive testing; and several others are on the way. The purported efficacy of these agents is the result of their interference with specific targets that lead to psoriasis.
Infliximab is effective in most patients, works quickly, and results in long-lasting remissions (in most cases, over 6 months). It can be administered with methotrexate and is not associated with nephrotoxicity or hepatotoxicity. Infliximab's drawbacks are several: it has to be administered by I.V. infusion over a period of at least 2 hours, infusion reactions are common, and patients occasionally develop antibodies that result in an increased frequency of side effects. There have been reports of serum sickness, and there is concern over increased susceptibility to infection, specifically to tuberculosis. Once approved, the drug may cost approximately $12,000 to $20,000 annually.
Etanercept results in dramatic and rapid improvement of psoriatic arthritis and, like infliximab, can be given with methotrexate. Etanercept is administered by patients at home at a dosage of 25 mg twice a week S.C. Its drawbacks include the development of non-neutralizing antibodies, antinuclear antibodies, anti-double-stranded DNA, and anticardiolipin antibodies. There have been rare reports of lupus erythematosus, but in all instances, major organs and systems such as the kidney and the CNS have been spared.
The main adverse reaction has been the development of injection-site reactions, which occurred in over a third of rheumatoid arthritis patients treated with etanercept and in 9% of psoriasis patients. Exacerbations of demyelinating diseases such as optic neuritis and multiple sclerosis have occurred, and there is concern about susceptibility to infection in patients treated with TNF- blockers. There are currently no recommendations for monitoring patients on etanercept. However, the emergence of tuberculosis in patients treated with TNF- inhibitors warrants that baseline purified protein derivative values and, if necessary, chest x-ray be obtained. Etanercept costs approximately $12,000 to $20,000 a year.
Alefacept, which has been recommended for approval by an FDA panel, results in extremely long remissions. Although CD45RO+ T cells are reduced, naive cells are unaffected. In over 1,500 patients treated with several courses over a few years, there has not been a single instance of opportunistic infection. Unfortunately, not everyone treated with alefacept experiences clearing of psoriasis. Another perceived drawback is the need to return to the physician's office each week for an intramuscular or intravenous injection. Moreover, the response to this drug is slow, with peak response occurring weeks after a 12-week treatment course; some patients experience further improvement with additional therapy.
Efalizumab, like etanercept, has the advantage that patients administer it subcutaneously at home, once a week. There is no hepatotoxicity and no nephrotoxicity associated with the use of this drug, but like all of the other biologics, it is likely to be expensive, and unlike the others, patients may experience exacerbations in psoriasis upon discontinuation of the drug, necessitating long-term therapy.
The nomenclature of the biologics is clinically important. Drugs that end in the letters mab are monoclonal antibodies. If they end in ximab, they are chimeric monoclonal antibodies and therefore may form neutralizing antibodies. Drugs that end in the letters zumab are humanized monoclonal antibodies and are therefore less likely to result in formation of neutralizing antibodies. Drugs ending in the letters cept involve the fusion of a receptor to the Fc portion of human IgG1.
Abandonment of current psoriasis treatment is not likely to occur. Safe and effective options still remain, including 80-year-old ultraviolet B phototherapy, one of the safest treatments available.
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Mark Lebwohl, MD, Mount Sinai School of Medicine
WebMD Scientific American® Medicine 2003.
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