Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Long-term low-level topical anti-inflammatory therapy has been suggested as a new paradigm in the treatment of atopic eczema (AE). OBJECTIVES: To determine the efficacy and tolerability of topical corticosteroids and calcineurin inhibitors for flare prevention in AE. METHODS: Systematic review of randomized controlled trials reporting efficacy of topical corticosteroids and/or topical calcineurin inhibitors for flare prevention in AE. Identification of relevant articles by systematic electronic searches (Cochrane Library, Medline) supplemented by hand search. Primary efficacy endpoint: proportion of participants experiencing at least one flare during proactive anti-inflammatory treatment. Relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated and pooled by pharmaceutical agent using random-effects meta-analysis. Sensitivity analysis included meta-regression to explore the influence of study-specific covariates. RESULTS: Nine articles reporting on eight vehicle-controlled trials were included. Three, four and one trial(s) evaluated proactive therapy with topical tacrolimus, fluticasone propionate and methylprednisolone aceponate, respectively. Each agent under study was more efficacious to prevent flares than vehicle. Meta-analysis suggested that topical fluticasone propionate (RR 0·46, 95% CI 0·38-0·55) may be more efficacious to prevent disease flares than topical tacrolimus (RR 0·78, 95% CI 0·60-1·00). Meta-regression indicated robustness of these findings. Proactive anti-inflammatory therapy was generally well tolerated. The trials identified, however, do not allow firm conclusions about long-term safety. CONCLUSIONS: Vehicle-controlled trials indicate efficacy of proactive treatment with tacrolimus, fluticasone propionate and methylprednisolone aceponate to prevent AE flares. Indirect evidence from vehicle-controlled trials suggests that twice weekly application of the potent topical corticosteroid fluticasone propionate may be more efficacious to prevent AE flares than tacrolimus ointment. Head to head trials should be conducted to confirm these results. Future studies are also needed to evaluate the long-term safety of proactive treatment of AE.