New oral psoriasis agents show promise

September 1, 2004

New York - While acitretin remains a common oral treatment for psoriasis, oral tazarotene (Allergan), fumaric acid esters (FAEs), and oral pimecrolimus can cut side effects ranging from alopecia to liver and kidney damage, according to a recent study.

New York - While acitretin remains a common oral treatment for psoriasis, oral tazarotene (Allergan), fumaric acid esters (FAEs), and oral pimecrolimus can cut side effects ranging from alopecia to liver and kidney damage, according to a recent study.

In the study, oral tazarotene 4.5 mg offers dramatic benefits over a placebo (Koo J, et al. Poster presented at AAD Academy 2003: Chicago).

In such studies, says Mark Lebwohl, M.D., "One of the things that's misunderstood is that the FDA has certain endpoints which require patients to be clear or almost clear. That was achieved in only about 20 percent of treated patients. But if you look at the patients who achieved a 50 percent or greater improvement in overall lesion assessments, there were 54 percent at 12 weeks."

Side effects Like other retinoids, oral tazarotene can cause cheilitis. Oral tazarotene also carries a minor risk of osteophyte formation and bone mineral density reductions. Unlike other retinoids, however, the drug causes no alopecia, no elevation of serum lipids and no hepatotoxicity.

"And the drug has a half-life of seven to 12 hours," Dr. Lebwohl says. "So, if it were to be used in women of childbearing potential, the period during which they couldn't become pregnant would be much shorter. And the safety in terms of teratogenicity would be much greater. Basically, when they stop it, within a month, there's no longer any risk (of birth defects). It has an even shorter half-life than Accutane (isotretinoin, Roche)."

Fumaric acid esters Fumeric acid esters (FAEs), on the other hand, rank among the most commonly prescribed oral psoriasis treatments in Germany.

"The problems with FAEs have been GI complaints and flushing," Dr. Lebwohl says.

In a recent study involving 83 patients, 31 discontinued treatment, nine because of side effects. These included flushing, gastrointestinal problems and reduction of lymphocytes (Thio HB et al. J Acad Dermatol Venereol. 1995;4:35-40).

A more recent study regarding long-term safety shows 55 percent of patients suffered flushing; 42 percent, diarrhea; 14 percent, nausea (Hoefnagel JJ et al. Br J Dermatol. 2003;149:363-369). The same study revealed lymphocyte-count reductions in 76 percent of patients, increased eosinophil counts in 14 percent of patients, and liver function test increases in 25 percent of patients.

Improved tolerability However, Biogen has acquired a new oral formulation of the drug (BG-12 oral fumarate) that is said to offer improved tolerability.

"The old agent, Fumaderm (Handels GmbH), is a mixture of fumaric acid esters, while BG-12 is a single ester," explains Dr. Lebwohl. "The adverse events of BG-12 are flushing and an elevation of the ALT. Gastrointestinal symptoms are uncommon."

A Phase 2b dose-ranging study in patients with severe psoriasis shows impressive results versus a placebo. In particular, 64 percent of patients reached PASI 50 scores at 12 weeks. Likewise, 42 percent of patients achieved PASI 75 at the same interval.

Oral pimecrolimus Oral pimecrolimus (Elidel, Novartis) also has been shown to achieve dramatic reductions in PASI scores, without typical cyclosporine side effects such as reduced renal function or blood pressure.

According to a 28-day dose-ranging study, more than 60 percent of patients at 60 mg/day achieved PASI 50 scores, while approximately 50 percent achieved PASI 75, and nearly 40 percent achieved PASI 90 (K. Rappersberger et al. J Invest Dermatol. 2002;119:876-887).

As for conventional systemic therapies, physicians often use folic acid to reduce nausea associated with methotrexate. However, studies done with rheumatoid arthritis and with psoriasis show that while folic acid appears to reduce methotrexate's side effects, it also mildly impairs the drug's efficacy.

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