Hand eczema: Oral alitretinoin can clear difficult-to-treat cases

November 1, 2009

According to new data, oral alitretinoin can clear severe chronic hand eczema.

Key Points

International report - Severe chronic hand eczema (CHE) has always been difficult to treat. But new data show that oral alitretinoin (Toctino, Basilea Pharmaceutica) is effective and safe in treating severe CHE, offering a good therapeutic option for those cases recalcitrant to standard therapies (such as emollients and potent topical corticosteroids).

Study details

A recent three-armed clinical study evaluated the efficacy and safety of oral alitretinoin in patients who suffer from severe CHE, and who are unresponsive to potent topical steroids and non-medicated skincare. Study A (the BACH study – Benefit of Alitretinoin in Chronic Hand Eczema) was a double-blinded, placebo-controlled trial performed in 111 centers in Europe and Canada that randomized 1,032 patients to receive 10 mg or 30 mg of alitretinoin or placebo once daily for 12 or 24 weeks.

Study C was a follow-up study that divided patients from the BACH study into two cohorts. Cohort A randomized 117 patients who initially responded to alitretinoin therapy in the BACH study but relapsed within 24 weeks to receive the same dose of alitretinoin or placebo. Cohort B included 243 patients who previously did not respond to therapy in the BACH study. These patients were reassigned to receive 30 mg of alitretinoin. A complete response was defined as "clear" or "almost clear" of symptoms.

Results

Results of Study A showed that complete response rates were significantly higher in the 30 mg and 10 mg groups (48 percent and 28 percent, respectively) compared to the placebo group (17 percent). The results of Study B showed that 116 patients (47 percent) achieved a complete response, and 159 patients (64 percent) were classified as at least partial responders, defined as "clear," "almost clear" or "mild disease."

Results of Study C showed a complete response rate in 80 percent of the patients in Cohort A who were treated with 30 mg of alitretinoin, compared to 8 percent for placebo. In patients retreated with alitretinoin 10 mg, response rates were 48 percent, compared to 10 percent in the placebo group. In Cohort B, almost half of non-responders from the BACH study demonstrated a complete response when retreated with 30 mg alitretinoin.

"Potent topical corticosteroids, ultraviolet therapies and even immunosuppressive treatments like cyclosporine A are all used in CHE; however, these can all have a less-than-optimal response, especially in severe CHE cases. Alitretinoin represents an excellent therapeutic option for those patients who are intensively pretreated with other approaches and do not respond or do not respond well to them," says Uwe Hillen, M.D., department of dermatology, University Clinic, Essen, Germany, and clinical investigator in the study.

Adverse events

Headache was the most common adverse event seen in the study and was the main reason for patient withdrawal. However, this adverse event was dose-dependent, as it was more commonly seen in those patients who received higher doses of the drug (30 mg).

Besides headache, laboratory abnormalities included elevated cholesterol and triglyceride levels. However, these side effects were easily controlled and managed through dose adaptations. Another safety concern with retinoid drugs is their potential teratogenicity.

"Alitretinoin is a retinoid drug, and the safety and tolerability profile seen is in line with that anticipated for this class of drugs. Like all retinoids, alitretinoin is a teratogen. This requires specific and effective pregnancy-prevention measures for women of childbearing potential. Our anticipation of a U.S. commercialization is that alitretinoin will follow measures for the management of the teratogenic risk similar to those established for isotretinoin," says Juergen Maares, M.D., global head of drug safety at Basilea Pharmaceutica International, the market authorization holder for Toctino, based in Basel, Switzerland.

According to Dr. Maares, patients who relapse and are subsequently re-treated with alitretinoin demonstrate a very good response to the re-treatment. The adverse event profile reported for patients who received a second course of treatment was similar to the first treatment course, with no late-arising toxicities reported.

Dr. Maares says CHE is a chronic inflammatory skin condition that may require chronic intermittent interventions.

"Alitretinoin can be seriously considered in those patients with severe CHE recalcitrant to standard highly potent topical corticosteroids, and can be used as an intermittent treatment option for the long-term management of this chronic and challenging-to-treat disease," Dr. Hillen tells Dermatology Times.

Oral alitretinoin is marketed in the United Kingdom, Denmark and Germany and is approved in Austria, Belgium, Finland, France, Luxemburg, the Netherlands and Spain. Alitretinoin has been recommended for approval in Italy and is under regulatory review in Canada and Switzerland. A Marketing Authorization Application (MAA) has been submitted to 15 additional European countries. A phase 3 study to support a U.S. filing for oral alitretinoin is currently under way.

Disclosure: Dr. Maares is a research physician and global head of drug safety at Basilea Pharmaceutica, which sponsored the clinical studies with oral alitretinoin in patients with severe CHE. Dr. Hillen was an investigator in the clinical trial.