By Chris Berrie
VIENNA, AUSTRIA -- May 22, 2007 -- Once-daily oral administration of the retinoid alitretinoin (9-cis retinoic acid) shows good tolerability and efficacy over placebo in patients with chronic hand eczema (CHE) that is refractory to current treatment options.
This international, prospective, randomised, double-blind, placebo-controlled, parallel-group, phase 3 study was presented here on May 17th at the 16th European Academy of Dermatology and Venereology Congress (EADV).
Jürgen Maares, MD, project physician and head, clinical science and medical affairs, development, Basilea Pharmaceutica AG, Basel, Switzerland, presented the findings on behalf of the Benefit of Alitretinoin in Chronic Hand Dermatitis (BACH) study investigators.
CHE is a severely debilitating disease and has a great impact on occupation and work ability, while also impairing the patient's private and social functioning. There are limited options available for patients who do not respond to established topical treatments.
"It is known that retinoids have an effect on skin diseases, with the heritage of the retinoids going back almost 30 years," said Dr. Maares, "while more recently surprising good efficacy was seen in the indication of alitretinoin for chronic hand dermatitis."
Dr. Maares and colleagues designed their study to determine whether 10-mg and 30-mg doses of alitretinoin are superior to placebo following 12 and 24 weeks of treatment.
Patients in the study had severe CHE as defined by the Physician Global Assessment (PGA) that was refractory to potent topical steroids. Dr. Maares stressed, "Patients at inclusion were chronic, with at least 6 months of disease, although in practice, in reality, the mean duration of disease was some 9 years, so it is a really chronic condition."
In addition, patients in the study had treatment failure while on the most potent steroids, and were refractory to the avoidance of skin irritants or allergens identified.
Following the eligibility prescreening, 1,032 patients were randomised to placebo (n = 205) or 10-mg (n = 418) or 30-mg alitretinoin (n = 409), given once daily for 12 or 24 weeks, depending on response to treatment. A standard emollient was provided for application several times a day.
Patients' mean age was 47.9 years in the placebo group (male, 59.0%), 47.3 years in the 10-mg group (male, 56.9%), and 48.5 years in the 30-mg group (male, 54.5%).
The baseline clinical characteristics across these 3 treatment groups were fairly well balanced, including duration of disease and disease phenotypes (respectively): hyperkeratotic (82.9%, 86.6%, 85.3%), pompholyx (26.8%, 26.6%, 27.1%), fingertip (49.3%, 43.1%, 47.9%), and other (14.1%, 14.5%, 13.4%).
As alitretinoin is a teratogen, females of child-bearing potential who took part underwent a pregnancy prevention programme.
The primary endpoint of PGA response rates at end of therapy was percentage of responders clear or almost clear of disease, with increasing significant improvements seen for placebo (17%, P <.001) and 10-mg (28%, P =.004) and 30-mg (48%, P <.001) alitretinoin.
This dose-dependent efficacy was confirmed for the secondary endpoint (respectively): Patients' Global Assessment (PaGA; percentage patients with clearing; 15%, 24%, 40%) and median percentage reductions in modified Total Lesion Symptom Score (mTLSS; 39%, 56%, 75%) and extent of disease (33%, 50%, 75%).
Treatment-related adverse effects were seen in 34.5%, 37.1%, and 49.5% of patients, respectively. Only 1.0% of patients in each treatment group reported severe adverse effects. One patient in the 10-mg alitretinoin group died.
Dr. Maares noted that, although the adverse effects showed a wide range, "The driver of the adverse events at the higher dose was headache," at 6.4%, 10.8%, 19.8%, respectively.
There were retinoid class effects that fell outside the protocol-defined ranges, with the worse being (respectively): high cholesterol (3.2%, 3.1%, 14.2%), high triglycerides (2.4%, 3.5%, 7.7%), and low thyroid-stimulating hormone (2.0%, 5.3%, 6.9%).
These data thus confirm that once-daily oral administration of alitretinoin provided dose-dependent response rates and times to response, along with some adverse effects that included typical retinoid and rexinoid effects. Thus, alitretinoin indeed showed tolerability and efficacy for the treatment of patients with CHE who were refractory to current treatment options.
This study was supported by Basilea Pharmaceutica AG.
[Presentation title: Efficacy and Safety of Alitretinoin (9-Cis Retinoic Acid) in Severe Chronic Hand Eczema Refractory to Topical Treatment (BACH Study). Abstract P275]
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