Topical calcineurin inhibitors in the treatment of atopic dermatitis: a meta-analysis of current evidence.
OBJECTIVE
To summarize success rates of the topical calcineurin inhibitors tacrolimus and pimecrolimus in treating atopic dermatitis.


METHODS
Randomized controlled trials (RCTs) comparing either drug to themselves (i.e. dose-ranging studies), each other, the vehicle (or placebo), or corticosteroids were obtained from Medline, EMBASE, and Cochrane databases. Two reviewers identified studies and extracted data, a third reviewer adjudicated disagreements. Outcomes included success, as defined by 90%, 75%, or 50% reductions from baseline in Eczema Area and Severity Index (EASI) scores or equivalent at 1, 3, 6, and 12 months, and also the difference between drug and vehicle (placebo). Rates were combined using a random effects meta-analytic model.


RESULTS
Of 180 articles identified, 165 were rejected (142 not RCTs/inappropriate outcome, 23 inappropriate/unextractable data). We included 15 articles reporting on 16 trials (nine tacrolimus and seven pimecrolimus trials) involving a total of 5301 patients, of whom 2107 received tacrolimus, 1225 received pimecrolimus and 1969 patients were controls. Tacrolimus reduced EASI scores by 65.6% at 1 month and 73.0% at 3 months; pimecrolimus reduced scores by 61.5% at 1 month, 60.3% at 6 months, and 61.9% at 12 months. When the difference in EASI score reductions were compared between active drug and placebo, tacrolimus success was 51.5% above placebo at 1 month and pimecrolimus was 45.9% higher at 1 month, 24.9% at 6 months, and 16.1% at 12 months.


CONCLUSIONS
Success rates for tacrolimus and pimecrolimus were statistically similar. However, tacrolimus rates were consistently higher numerically than those for pimecrolimus, and tacrolimus was used in patients with more severe disease. A head-to-head RCT is required to determine if true differences exist between these drugs.
Iskedjian
Michael
M
PharmIdeas Research & Consulting Inc., Oakville, Ontario, Canada.
Piwko
Charles
C
Shear
Neil H
NH
Langley
Richard G B
RG
Einarson
Thomas R
TR
D000279:Administration, Cutaneous; D065095:Calcineurin Inhibitors; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D016559:Tacrolimus