Topical calcineurin inhibitors in atopic dermatitis: A systematic review and meta-analysis

Objectives: To build a critical appraisal of the available literature to evaluate the effectiveness of topical calcineurin inhibitors in treatment of atopic dermatitis (AD), in comparison to topical corticosteroids (TCs) and/or placebo. Review methods: Design: systematic review and meta-analysis. Data sources: electronic search of MEDLINE Pubmed along the last 10 years (1997-2006). Study selection: randomized control trials of TCIs reporting efficacy outcomes, in comparison to TCs or vehicle (placebo) or both. Data synthesis: of 210 articles, 19 studies were included, 10 for tacrolimus and 9 for pimecrolimus. involving 7378 patients of whom 2771 applied tacrolimus, 1783 applied pimecrolimus, and 2824 were controls. Both drugs were significantly more effective than a vehicle. However, two long-term trials comparing demonstrated the value of pimecrolimus in reduction of flares and steroid-sparing effect after 6 months. Compared to TCs, both 0.1% and 0.03% tacrolimus ointments were as effective as moderate potency TCs, and more effective than a combined steroid regimen. Tacrolimus was more effective than mild TCs. Conclusions: TCIs in AD are more effective than placebo. Although less effective than TCs, pimecrolimus has its value in long-term maintenance and as a steroid-sparing agent in AD, whenever used early enough, at first appearance of erythema and/or itching. In treatment of moderate to severe AD, topical tacrolimus is as effective as moderately potent TCs, and more effective than mild preparations. Chronic AD lesions of the face and flexures are the most justified indication for topical calcineurin inhibitors. (C) 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.