There is little doubt that topical tacrolimus is an effective drug for atopic eczema when compared with vehicle, with some slight gains in efficacy for the stronger 0-1% preparation. The drug appears to be safe in the short term, although it should be borne in mind that tacrolimus is a potent immunosuppressive and more data will be needed on skin infections such as herpes simplex and eczema herpeticum. Longer-term surveillance data will also be needed on subsequent risk of internal malignancies. Given that topical tacrolimus is likely to be applied frequently to facial skin, this being a frequent site for atopic eczema involvement, there is a need to carefully evaluate the risk of excess skin cancer on areas of the skin exposed to the sun.
Topical tacrolimus is a welcome addition to the physician's armamentarium for this troublesome disease. What is less clear for the practising physician is where topical tacrolimus fits in with the other currently available therapies, most notably the topical corticosteroids - an obvious point noted by others.15
Topical tacrolimus has been licensed in the US and UK for the treatment of people with moderate-to-severe atopic eczema that is not adequately responsive or who are intolerant of conventional therapies. Rather oddly, however, none of the RCTs has been conducted specifically in people in whom topical steroids have failed. This raises the question of why product licenses were granted for such second-line use, given the lack of relevant evidence to inform such a decision. The percentage of atopic eczema sufferers who are truly "unresponsive" to topical steroids is probably very small (around 10% of severe cases seen in secondary care).16 It is likely, therefore, that the drug will be used in a much wider group of atopic eczema patients as an alternative to topical corticosteroids - a prediction that is likely to be fulfilled given existing widespread and often unjustified public fear of using topical steroids.16
The lack of skin thinning with prolonged use of topical tacrolimus is a distinct advantage over topical steroids when the latter have to be used in excessive quantities for sites that are prone to skin thinning, such as the face. Even so, clinically significant skin thinning with intermittent use of topical steroids is exceedingly rare in modern clinical practice. Some case series have suggested good response of facial atopic eczema and atopic blepharitis to topical tacrolimus,18-20 and these may be two scenarios in which the drug will prove to be particularly useful.
In terms of comparison with topical steroids, the physician is still left with considerable difficulty in deciding when to use topical tacrolimus. The study by Reitamo et at8 suggested that topical tacrolimus is more effective that 1% hydrocortisone acetate, but this is hardly a fair comparison given that 1% hydrocortisone is very weak and arguably an inappropriate and unethical treatment for people with severe atopic eczema.8 Three short-term studies have compared 0-1% tacrolimus against potent topical steroids and found it to be equivalent in terms of efficacy.9-11 It might have been more appropriate to test topical tacrolimus against short bursts of a modern once-daily potent topical steroid such as mometasone or fluticasone over a long period so that the effects of disease chronicity and clinically important skin thinning could be evaluated.
Tacrolimus has not been compared head to head with ascomycin (syn. pimecrolimus), a closely related topical preparation, which is manufactured by another company. This lack of head-to-head comparison seems odd for two such similar drugs competing for the same market. This may be because tacrolimus is aimed at the more severe end of the spectrum in secondary care, with pimecrolimus targeting the much bigger market of primary care.
No data on cost-effectiveness is available, and topical tacrolimus is at least ten times more expensive at present than topical steroids. None of the efficacy studies has been sufficiently long to evaluate effects on disease chronicity.
In view of the above concerns, two key studies are needed:
• a comparison of topical tacrolimus, ascomycin and continued use of topical steroids (with or without bandaging) in people with severe atopic eczema inadequately responsive to topical steroids
• a long-term pragmatic RCT of topical tacrolimus versus topical ascomycin versus standard practice of intermittent use of a potent topical steroid such as fluticasone propionate. Such a study should capture disease chronicity and cost-effectiveness and employ simple categorical patient-derived outcome measures.
None of the studies has been conducted independently of the manufacturers, and it is not clear how many unpublished or ongoing studies exist.
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