Efficacy and Tolerability of Pimecrolimus and Tacrolimus in the Treatment of Atopic Dermatitis: Meta-analysis of Randomised Controlled Trials

Abstract

Purpose of the Study. To determine the efficacy and tolerability of topical pimecrolimus and tacrolimus compared with other treatments for atopic dermatitis. Methods. Randomized, controlled trials of topical pimecrolimus or tacrolimus reporting efficacy outcomes or tolerability from the Cochrane Library, Medline, and Embase were identified. Eligible trials were evaluated for efficacy, identified as investigators’ global assessment of response; patients’ global assessment of response; proportions of patients with flares of atopic dermatitis; and improvements in quality of life. Trials were also evaluated for tolerability, identified as overall rates of withdrawal, withdrawal resulting from adverse events, and proportions of patients with burning of the skin and skin infections. Results. A total of 4186 of 6897 participants in 25 randomized, controlled trials received pimecrolimus or tacrolimus. Both drugs were significantly more effective than a vehicle control. Tacrolimus 0.1% was as effective as potent topical steroids at 3 weeks and more effective than combined treatment with hydrocortisone butyrate 0.1% plus hydrocortisone acetate 1% at 12 weeks (number needed to treat [NNT]: 6). Tacrolimus 0.1% was also more effective than hydrocortisone acetate 1% (NNT: 4). In comparison, tacrolimus 0.03% was more effective than hydrocortisone acetate 1% (NNT: 5) but less effective than hydrocortisone butyrate 0.1% (NNT: −8). Direct comparisons of tacrolimus 0.03% and tacrolimus 0.1% consistently favored the higher strength formulation. Pimecrolimus was far less effective than betamethasone valerate 0.1% (NNT: −3 at 3 weeks). Conclusions. Both topical pimecrolimus and topical tacrolimus are more effective than placebo treatments for atopic dermatitis, but in the absence of studies that show long-term safety gains, any advantage over topical corticosteroids is unclear. Topical tacrolimus is similar to potent topical corticosteroids and may have a place for long-term use in patients with resistant atopic dermatitis on sites at which adverse effects from topical corticosteroids might develop quickly. In the absence of key comparisons with mild corticosteroids, the clinical need for topical pimecrolimus is unclear. The usefulness of either treatment in patients whose conditions have failed to respond adequately to topical corticosteroids is also unclear. Reviewer Comments. With the recent worry of “black-box” warnings on these medications, it is useful to see a meta-analysis of controlled trials on pimecrolimus and tacrolimus as an alternative to steroids in the treatment of atopic dermatitis. The results of this study suggest that the usefulness of either treatment in patients whose conditions have failed to respond to topical corticosteroids is unclear but that they may provide an alternative to steroids in certain clinical scenarios. One should keep in mind the risk/benefit ratio of all immunosuppressive medications in the treatment of atopic dermatitis.