Intermittent Therapy for Flare Prevention and Long-term Disease Control in Stabilized Atopic Dermatitis: A Randomized Comparison of 3-Times-Weekly Applications of Tacrolimus Ointment Versus Vehicle
Breneman D, Fleischer AB Jr, Abramovits W, et al. J Am Acad Dermatol. 2008;58(6):990–999
PURPOSE OF THE STUDY. To determine the efficacy and safety of 3 times per week maintenance use of tacrolimus in the prevention of atopic dermatitis (AD) exacerbations.
STUDY POPULATION. Multicenter, randomized, double-blind, placebo-controlled study of 383 patients over the age of 2 years with moderate-to-severe AD.
METHODS. The study consisted of stabilization and maintenance phases. During stabilization, subjects received tacrolimus ointment (0.03% [2–16 years] or 0.1% [>16 years]) or corticosteroid (alclometasone diproprionate, 0.05% ointment [2–16 years], or triamcinolone acetonide, 0.1% ointment [>16 years]) twice daily for 4 days at AD flare sites, followed by a 2-week, open-label phase. Subjects demonstrating a response to tacrolimus were then asked to participate in the maintenance portion of the study. The maintenance phase was a randomized, double-blind, vehicle-controlled, 40-week study in which topical application was performed once daily, 3 times per week, at previous eczema flare sites.
RESULTS. Subjects receiving tacrolimus experienced more symptom-free days (177 vs 134 days; P = .003). Time to relapse was longer in patients treated with tacrolimus versus vehicle (169 vs 43 days; P = .037). Patients receiving tacrolimus seemed less likely to experience relapse (62% vs 66% with ≥1 relapse during treatment; P = .55) and had fewer relapses during the treatment period (maximum of 3 relapses in 5.6% of the tacrolimus group versus 3–6 relapses in 16.9% of the vehicle group). The severity of relapses was milder in the treatment group, with only 29% in the tacrolimus group having moderate relapse, compared with 51% in the vehicle group. During the open-label trial, 83% of patients in both the tacrolimus and vehicle groups responded to tacrolimus treatment of relapse. With regard to safety, patients treated during the stabilization phase with tacrolimus versus topical steroid were more likely to have cutaneous site reactions (18% vs 9%; P = .015) during the first 4 days of treatment; this was not seen during the rest of the treatment course.
CONCLUSIONS. Tacrolimus maintenance therapy increased the number of symptom-free days and the time to relapse, compared with vehicle alone.
REVIEWERS COMMENTS. AD is a disease characterized by intermittent flares and symptom-free periods. Maintenance, intermittent, topical corticosteroid dosing regimens have been successful in preventing relapse. The use of maintenance steroid-sparing therapies is desirable. This study indicates that maintenance therapy may prevent relapse occurrence and decrease the severity of disease and provides an interesting treatment option for patients with AD with frequent relapses. Also, in light of recent Food and Drug Administration warnings concerning topical calcineurin inhibitors, it is valuable to know that dosing could be reduced to 3 times weekly for maintenance. Overall, this well-designed study provides convincing support for maintenance therapy of AD with topical nonsteroidal calcineurin inhibitors. Similar results were seen in 3 other studies using 2 or 3 times per week dosing schedules for topical steroids and topical calcineurin inhibitors. These studies indicate that maintenance therapy is superior to as-needed use of topical medications for patients with moderate-to-severe AD.
- Copyright © 2009 by the American Academy of Pediatrics