Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use.
OBJECTIVE
Long-term, safe and effective therapeutic options for managing the chronic relapsing nature of atopic dermatitis are essential for improving patient quality of life. To minimize the risks of continued topical corticosteroid usage and potentially reduce the incidence of flares, we tested the efficacy and safety of a rotational paradigm of initial brief application of topical corticosteroid followed by long-term intermittent application of non-steroidal tacrolimus ointment to previously inflamed sites of dermatitis.


METHODS
In this 2-phase study, patients who were 2 to 15 years of age and had moderate to severe atopic dermatitis were randomly assigned to 4 days of twice-daily double-blind therapy with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (Phase I acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (Phase I short-term). Patients whose disease stabilized underwent new randomization to double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week to clinically normal-appearing skin for up to 40 weeks (Phase II). Corticosteroid use was prohibited.


RESULTS
Of 206 randomly assigned patients, 152 completed Phase I; 105 of 152 were randomly assigned into Phase II (68 tacrolimus ointment and 37 vehicle). There were no differences in adverse events between alclometasone and tacrolimus (Phase I) or between tacrolimus and vehicle (Phase II). In the acute period, alclometasone-treated patients showed greater improvement in atopic dermatitis signs and symptoms; thereafter, when all patients applied tacrolimus ointment (short-term), there were no differences. In Phase II, tacrolimus-treated patients had significantly more disease-free days compared with vehicle, significantly longer time to first relapse, and significantly fewer disease relapse days.


CONCLUSIONS
For patients with stabilized moderate to severe atopic dermatitis, long-term intermittent application of tacrolimus ointment to normal-appearing but previously affected skin was significantly more effective than vehicle at maintaining disease stabilization, with a safety profile similar to vehicle.
Paller
Amy S
AS
Department of Dermatology, Northwestern University's Feinberg Medical School/Children's Memorial Hospital, 676 North St Clair St, Suite 1600, Chicago, IL 60611, USA. apaller@northwestern.edu
Eichenfield
Lawrence F
LF
Kirsner
Robert S
RS
Shull
Toni
T
Jaracz
Eileen
E
Simpson
Eric L
EL
D000287:Administration, Topical; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D015999:Multivariate Analysis; D009824:Ointments / Q000627:therapeutic use; D011336:Probability; D018570:Risk Assessment; D055502:Secondary Prevention; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D009824:Ointments; D016559:Tacrolimus