The quality of reporting of the pimecrolimus studies was generally good. In the third study of pimecrolimus versus vehicle in children, it is unclear why separate but identical multicentre studies were initially set up by the sponsoring company and then combined in a final analysis.8 The study was reasonably reported, except that the method of randomisation and subsequent concealment and the success of blinding were unclear. It was also unclear whether participants were allowed to use any concomitant treatments such as emollients or rescue therapy for uncontrolled flares (which would have been likely given that 65% "failed" to achieve "success" in the pimecrolimus group).
Topical pimecrolimus has not been compared head to head with topical tacrolimus. However, there is a hint from the second RCT that pimecrolimus is not as effective as potent topical corticosteroids that are of similar strength to tacrolimus.7,12 This may explain why pimecrolimus has been targeted for mild-to-moderate atopic eczema.
So far, all we are able to say is that 1% pimecrolimus cream is more effective than placebo and that it is much less effective than a potent topical steroid. It appears safe in the RCTs that have been conducted to date, although these are not suitable for excluding long-term rare and more serious risks such as internal and skin malignancies, however unlikely they may seem due to current known mechanisms.
As with tacrolimus, the manufacturers have not performed a long-term study comparing pimecrolimus against typical current best treatment of bursts of potent or even mild topical steroids, and no cost-effectiveness data are available for such head-to-head comparisons. Pimecrolimus has not been evaluated in patients in whom topical corticosteroid have failed, making it difficult to say whether it will be useful as a second-line agent.
As with tacrolimus, it is good to see new and effective topical treatments for atopic eczema that appear to be safe in the short term. What is more difficult for the prescribing physician or patient at the moment is to be clear about the indications for use of the drug in the absence of some key studies. The wording of the indications in the opening paragraph of this section are vague and unhelpful and could include every person with a concern about using topical corticosteroids, however unjustified that may seem.
It is also unclear from the studies whether pimecrolimus should be used continuously or intermittently for flares. The RCTs that have been conducted to date have used treatment regimens that involve applying the cream continuously for several weeks. A recently completed study (published in abstract form only at the time of writing) hints at another way in which the manufacturers may like to see pimecrolimus being used. This was a 6-month study involving 250 infants aged 3-23 months, in whom pimecrolimus was used as soon as the signs of eczema or itching occurred and was compared against a vehicle ointment to see how many flare ups requiring topical corticosteroids could be prevented.13 Only 32% of those in the control group were free from flare ups compared with 70% of those in the active group. Another similar study of 713 patients aged 2-17 years showed that 51% of those in the pimecrolimus group did not have flare ups requiring potent topical corticosteroids, compared with 28% using emollients only.14 At face value, both these studies appear convincing until one realises that they are effectively placebo-controlled studies. It could have been the case that early treatment with 1% hydrocortisone ointment would have averted the development of flares equally well. Again, the physician and patient is left guessing how pimecrolimus compares with best standard therapy.
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