Oral alitretinoin (Toctino) was launched in the UK in September 2008 for the treatment of severe chronic hand eczema unresponsive to potent topical corticosteroids, in adults.
It is the first product licensed specifically for the treatment of steroid-refractory chronic hand eczema (CHE).
Hand eczema is the most important occupational skin disease for a number of jobs that involve a lot of wet work or exposure to friction or irritants, such as nursing, hairdressing, food preparation, building and printing.
Alitretinoin is a retinoic acid derivative and is an agonist of both retinoic acid receptors (RAR) and retinoid X receptor (RXR).
Pregnancy is an absolute contra-indication to treatment with alitretinoin. Basilea Pharmaceuticals has put together a Pregnancy Prevention Programme, containing guidance on prescribing alitretinoin to women of child-bearing potential and contraceptive precautions required.
There have been two main phase 3 studies looking at the efficacy and safety of alitretinoin.
The BACH study enrolled 1032 patients with severe chronic hand eczema refractory to topical potent steroid treatment. Patients were randomised to 12-24 weeks of treatment with either alitretinoin 30mg or 10mg, or placebo. All patients were given an emollient to use several times a day. Responders were followed up for a further 24 weeks for relapse observation.
Response rates (‘clear’ or ‘almost clear’) were highest in the 30mg group (47.7%) compared with 27.5% in the 10mg group and 16.6% in the placebo group.
Time to response, median percentage reduction in the modified Total Lesion Symptom Score, partial response and median percentage reduction in the extent of the disease were significantly superior in the alitretinoin groups, compared with placebo. Median time to relapse (5-6 months) did not differ significantly between those patients who responded to 30mg (n= 195), 10mg (n= 115) or placebo (n=34).
The second phase 3 study assessed the efficacy of re-treatment with alitretinoin (or placebo) in patients who had responded during the BACH study but then relapsed during the 24-week follow-up period, during which no active treatment was permitted.
Patients who were treated with alitretinoin in both the BACH and the re-treatment study had substantially higher response rates than those given alitretinoin in the BACH study and then placebo in the re-treatment study. Patients who responded to placebo in the BACH study were re-treated with placebo, and response rates were higher than those who had been treated with alitretinoin 10mg in both studies (70% vs. 48%). 80% of patients who relapsed after the BACH study and who were retreated with 30mg alitretinoin successfully responded.
Main adverse events seen in the studies included headache, dry mouth and erythema. Increases in cholesterol and triglycerides occurred, as did asymptomatic changes in thyroid stimulating hormone levels. Adverse events were generally dose-dependent and reversible.