Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment.
Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2-15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of >or=60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was -11.8%, exceeding the non-inferiority limit of -15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 +/- 5.0 and 8.6 +/- 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep.
Doss
N
N
Department of Dermatology, Military Hospital of Tunis, Tunis, Tunisia. nejib.doss@voila.fr
Kamoun
M-R
MR
Dubertret
L
L
Cambazard
F
F
Remitz
A
A
Lahfa
M
M
de Prost
Y
Y
D000293:Adolescent; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D009824:Ointments; D011537:Pruritus / Q000188:drug therapy; D012008:Recurrence; D012893:Sleep Wake Disorders / Q000188:drug therapy; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000730:Androstadienes; D065095:Calcineurin Inhibitors; D003879:Dermatologic Agents; D009824:Ointments; D000068298:Fluticasone; D016559:Tacrolimus