Ruzicka T, Lynde CW, Jemec GBE et al. Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. British Journal of Dermatology 2008;158:808–17
Oral alitretinoin is a derivative of retinoic acid that has been recommended for regulatory approval in Europe for the treatment of severe refractory chronic hand eczema in patients unresponsive to potent topical steroids.
Alitretinoin is likely to be prescribed by specialists experienced in the use of systemic retinoids. Such drugs are teratogenic, therefore women of child-bearing potential who receive alitretinoin must be advised on pregnancy prevention measures.
Some limited data suggest a benefit over placebo in patients who have failed to respond to topical steroids. However, as yet, there is no published evidence for this agent compared with other treatment options used at this stage.
Update (posted 24/9/08)- alitretinoin has now been marketed in the UK. It costs £411.33 for 30 x 10mg/30mg capsules. The Summary of Product Characteristics (SmPC) can be found here.
What is the background to this?
Hand eczema is characterised by fissuring, hyperkeratosis and formation of vesicles and is associated with itching and pain . It often has a remitting and relapsing course and is associated with a poor response to treatment. The one-year prevalence is estimated to be up to 10% of the general population. Severe chronic hand eczema is seen in about 5 – 7% of all patients with hand eczema and 2 to 4% are refractory to topical treatments . Chronic hand eczema is often associated with exposure to irritants, such as oils, or allergens such as nickel. Hand eczema is the form of eczema most frequently associated with work disability . Oral alitretinoin (Toctino®) was marketed in the UK in September 2008 and is listed for an appraisal in the NICE 18th wave. It is the first oral agent to be authorised specifically for the treatment of chronic hand eczema. Further information on eczema is available on the skins floor of NPC.
What does this study claim?
In this double-blind, manufacturer-sponsored trial, 1,032 adults with severe chronic hand eczema refractory to potent topical corticosteroids were randomised in a 2:2:1 ratio to alitretinoin 10 or 30mg daily for up to 24 weeks or placebo. The primary efficacy outcome was Physician Global Assessment (PGA) of disease severity, with response defined as clear or almost clear hands in the intention-to-treat population. This outcome was seen in 34/205 placebo patients (16.6%), 195/409 (47.7%) of the 30mg alitretinoin group (P<0.001 vs. placebo) and 115/418 (27.5%) of the 10mg alitretinoin patients (P=0.004 vs. placebo). Time to relapse was included as a secondary outcome. This was a median of 5.5 months for the 30mg strength, 6.2 months for the 10mg group and 5.4 months for placebo patients.
Headache was the most common adverse event, occurring in 20% of the 30mg alitretinoin patients, 11% of the 10mg group and 6% of placebo patients. It was the most frequent adverse event leading to withdrawal from the study. Raised triglyceride levels were seen in 3% of the high dose group, 1% of the 10mg patients and in none of the patients receiving placebo. The incidence of dry lips, flushing and erythema appears to be dose-dependent.
Therapy normally follows a stepwise pattern starting with skin protection measures, moving to emollients, topical corticosteroids, coal tar, PUVA and topical immunomodulators. If none of these prove appropriate then the final step would be systemic treatments such as azathioprine, retinoids and oral corticosteroids in short courses . Alitretinoin has been studied in patients who have failed on topical corticosteroids; therefore it may be positioned to be used after topical steroids and before other systemic treatments. However, there are no head-to-head studies comparing alitretinoin with either PUVA or systemic drugs so its exact place in therapy remains to be elucidated.
According to the SmPC, the recommended starting dose is 30mg daily and a treatment course lasts 12 to 24 weeks, depending on response. As alitretinoin is a derivative of vitamin A, and retinoids are known teratogens, strict pregnancy prevention measures must be in place for all women of child-bearing potential who may receive the drug.
- Diepgen TL, Agner T, Aberer W et al. Management of chronic hand eczema. Contact Dermatitis 2007;57:203–10
- National Library for Health. Healthcare Needs Assessment. Dermatology. 1997. Available from URL: http://www.library.nhs.uk/skin/SearchResults.aspx?tabID=288&catID=9764. Accessed on 21/8/2008