Toctino

Basilea has launched Toctino (alitretinoin) for the treatment of severe chronic hand eczema (CHE) in adults unresponsive to treatment with potent topical corticosteroids.

PHARMACOLOGY
Alitretinoin is physiological, endogenous retinoid. Retinoids are derivatives of vitamin A that display key regulatory functions in epidermal growth and differentiation.

The exact mechanism of action of alitretinoin in the treatment of CHE is unknown, but it has demonstrated immunomodulatory and anti-inflammatory effects that are relevant to skin inflammation.

Unlike other retinoids, alitretinoin binds to members of both the RAR and RXR retinoic receptor families.

CLINICAL STUDIES
The efficacy and safety of alitretinoin has been evaluated in a pivotal phase III clinical study (BACH - Benefit of Alitretinoin in Chronic Hand Eczema) and a phase III re-treatment study.

In the BACH study,1 1032 patients diagnosed with severe refractory CHE were randomised to placebo, 10mg or 30mg of alitretinoin once daily for up to 24 weeks. The primary efficacy parameter for therapeutic response was the Physicians Global Assessment (PGA), performed at screening and every four weeks during treatment. Response was defined as a PGA assessment of clear or almost clear hands. Secondary efficacy parameters were time to response, partial response (defined as a PGA assessment of clear, almost clear or mild), the modified Total Lesion Symptom Score (mTLSS), the Patients Global Assessment (PaGA) of improvement, time to relapse and the extent of disease.

The study showed a significantly higher response rate in the alitretinoin 30mg (48%) and 10mg (28%) groups compared with placebo (17%), with clearly apparent dose dependence. Among responders, the proportion of patients rated as clear was significantly higher in the alitretinoin 30mg and 10mg groups compared with placebo.

By 24 weeks, there was a 75% and 56% median reduction in disease signs and symptoms among CHE patients receiving 30mg alitretinoin and 10mg alitretinoin, respectively, compared to 39% of patients on placebo (as measured by the mTLSS).

The most frequently reported adverse effect was headache, more common in the alitretinoin 30mg group than in the 10mg or placebo groups. The frequency of mucocutaneous events such as dry skin, dry lips and cheilitis also appeared to be dose dependent. The most frequent laboratory abnormalities were changes in triglycerides, cholesterol and TSH.

The re-treatment study2 assessed the efficacy and safety of a second 12-24 week course of alitretinoin in 117 patients with severe CHE refractory to topical therapy, who previously responded (PGA clear or almost clear hands) in the BACH study. Patients were randomised to receive a further 12 weeks to 24 weeks treatment with either placebo or their previous dose of alitretinoin.

The response rate, defined as clear or almost clear hands, in the re-treatment study was 80% for the 30mg group versus 8.3% for placebo and 48% for the 10mg group versus 10% for placebo.

Alitretinoin was generally well tolerated in the re-treatment study. Adverse effects generally corresponded to known retinoid class effects, consistent with observations in the BACH study with no new or cumulative toxicities observed.

View Toctino record

REFERENCES
1. Ruzicka T, Lynde C, Jemec G et al. Efficacy and safety of oral alitretinoin in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomised, double-blind, placebo-controlled, multicentre trial. British Journal of Dermatology April 2008; 158(4): 808-817.
2. Poster presentation: Ruzicka T, Lahfa M, Lynde C et al. Re-treatment study of alitretinoin (9-cis-retinoic acid) in severe chronic hand eczema refractory to topical treatment. EADV 2007 - Poster 280.

Further information: Basilea

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