Topical pimecrolimus for eczema Edited (no change to conclusions)

Abstract

Abstract Background

Pimecrolimus was developed as an alternative to topical corticosteroids for treating eczema (atopic dermatitis) but its efficacy and safety compared with existing treatments remains unclear.

Objectives

To assess the effects of topical pimecrolimus for treating eczema.

Search methods

We searched the Cochrane Skin Group Specialised Register (to October 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2006), MEDLINE (from 2003 to October 2006), and EMBASE (from 2005 to October 2006). We also contacted researchers and manufacturers in the field.

Selection criteria

Randomised controlled trials of 1.0% topical pimecrolimus used twice daily compared against other topical comparators for treating eczema.

Data collection and analysis

Two authors independently examined each retrieved study for eligibility and extracted data for efficacy, tolerability and safety. A random‐effects model was used to estimate the pooled risk ratios (RRs) and 95% confidence intervals (95% CIs).

Main results

We included 31 trials (8019 participants) in the analysis. In short‐term (≤ 6 weeks) trials, pimecrolimus cream was significantly more effective and well‐tolerated than vehicle (cream base, but not containing pimecrolimus). In long‐term trials (≥ 6 months), pimecrolimus was significantly better than vehicle in preventing flares (9 trials, 3091 participants, RR 1.47, 95% CI 1.32 to 1.64 at six months) and in improving quality of life. 
 
 Pimecrolimus was significantly less effective than two topical corticosteroids, i.e. 0.1% triamcinolone acetonide for investigators' global assessment (1 trial, 658 participants, RR 0.75, 95% CI 0.67 to 0.83) and 0.1% betamethasone valerate for participants' global assessment (1 trial, 87 participants, RR 0.61, 95% CI 0.45 to 0.81) at three weeks. Pimecrolimus was also associated with significantly more overall withdrawals and skin burning. None of the trials reported on key adverse effects such as thinning of skin.

Pimecrolimus was significantly less effective than 0.1% tacrolimus for investigators' global assessment at 6 weeks (RR 0.58, 95% CI 0.46 to 0.74) and led to more withdrawals due to lack of efficacy (RR 2.37, 95% CI 1.10 to 5.08) based on 2 trials involving 639 participants, but there was no significant difference in proportions of participants experiencing any adverse events.

Authors' conclusions

Topical pimecrolimus is less effective than moderate and potent corticosteroids and 0.1% tacrolimus. The therapeutic role of topical pimecrolimus is uncertain due to the absence of key comparisons with mild corticosteroids.

Author(s)

Darren M Ashcroft, Li‐Chia Chen, Ruth Garside, Ken Stein, Hywel C Williams

Abstract

Plain language summary

Topical pimecrolimus for eczema 

This review of clinical trials aimed to find out whether topical pimecrolimus is better than topical corticosteroids or tacrolimus for treating eczema in infants, children and adults by assessing the improvement of eczema and adverse events associated with treatments.

Eczema (atopic dermatitis) is a very common and long‐lasting skin disease caused by both genetic and environmental factors, and most often begins in infancy and childhood. Corticosteroid creams have been used to treat eczema but may cause unwanted side effects, including thinning of the skin. Pimecrolimus cream was developed as an alternative to topical corticosteroids, but it is much more expensive than corticosteroids. It is also not clear whether pimecrolimus is more effective or better tolerated than corticosteroids or a similar drug called tacrolimus.

This review included data from 31 clinical trials involving 8019 participants. In the short‐term (less than six weeks) treatment of eczema, we found pimecrolimus was more effective and well‐tolerated when compared against vehicle (cream base not containing any pimecrolimus). Likewise, pimecrolimus was better than vehicle cream in preventing deterioration in eczema based on data from 9 trials involving 3091 participants. However, we found that 3 weeks treatment with pimecrolimus was less effective than a moderate (triamcinolone acetonide, data from 1 trial with 658 participants) and a potent topical corticosteroid (betamethasone valerate, data from 1 trial with 87 participants). Furthermore, 6‐weeks treatment with pimecrolimus was less effective and caused more participants to drop out of treatment due to lack of efficacy than tacrolimus based on 2 trials involving 639 participants.

Pimecrolimus caused a similar rate of adverse events to vehicle cream but had a lower overall dropout rate. In contrast, pimecrolimus had higher dropout rates and caused more skin burning than topical corticosteroids. None of the trials reported on key adverse effects, such as thinning of skin. Pimecrolimus caused a similar rate of adverse events to tacrolimus. There were no cancer‐related events reported in any of the 31 clinical trials.

This review did not find evidence to support the notion that pimecrolimus was better than moderate or potent corticosteroids or tacrolimus in treating eczema. However, there is a distinct lack of trials comparing pimecrolimus against mild‐potency corticosteroids.

Author(s)

Darren M Ashcroft, Li‐Chia Chen, Ruth Garside, Ken Stein, Hywel C Williams

Reviewer's Conclusions

Authors' conclusions

Implications for practice

Our systematic review shows that pimecrolimus is effective when compared against vehicle with short bursts of topical corticosteroids for flare‐ups of eczema. However, there is limited evidence on the comparative efficacy, tolerability, and adverse events associated with pimecrolimus compared against existing optimal treatments, such as mild topical corticosteroids and tacrolimus. The clinical role of pimecrolimus is therefore uncertain owing to a lack of relevant comparative data. There is no evidence at present to suggest that pimecrolimus is effective in people who fail to respond to topical corticosteroids. Whilst topical pimecrolimus might have a useful role in treating eczema at sensitive sites such as the face where skin thinning may become a problem, no comparative studies have addressed this issue and demonstrated any advantage over existing therapy. Whilst short‐term studies on drug safety are reassuring, more long term studies evaluating the possible risks associated with skin immunosuppression are needed.

Implications for research

More vehicle controlled studies are not needed and may even be considered as unethical. Pragmatic randomised controlled trials lasting at least 12 months are needed to compare topical pimecrolimus and 1% hydrocortisone acetate in children and adults with mild to moderate eczema. More trials are needed to see if topical pimecrolimus works in people who fail to respond adequately to topical corticosteroids. Trials are needed that evaluate topical pimecrolimus in sensitive sites such as the face. Outcome data should include clearing capacity, relapse, quality of life, adverse events (including skin thinning), and costs. Although several trials have been undertaken on participants who responded poorly to topical corticosteroids, current evidence is insufficient to support using pimecrolimus as a second line treatment of eczema despite recommendation by the UK National Institute of Health and Clinical Excellence (NICE 2004) and the US Food and Drug Administration to use it in such circumstances (FDA 2005). Experience of long term use of topical pimecrolimus is limited and the risk of rare but more serious adverse effects remains a concern. Further long term surveillance of these agents is needed (Williams 2002).

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