Tacrolimus Ointment: Advancing the Treatment of Atopic Dermatitis
A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients,☆☆,,★★,,♢♢

https://doi.org/10.1067/mjd.2001.109813Get rights and content

Abstract

The safety and efficacy of 0.03% and 0.1% tacrolimus ointment for the treatment of atopic dermatitis were evaluated in a 12-week, randomized, double-blind, vehicle-controlled study of 351 children 2 to 15 years of age with moderate to severe atopic dermatitis. The mean age of patients was 6.1 years. A total of 61.5% of patients had severe atopic dermatitis at baseline. The mean percentage of body surface area affected was 47.7%, and 83.5% of patients were affected on the head and/or neck. Significantly more patients (P < .001) achieved clinical improvement of 90% or better with 0.03% or 0.1% tacrolimus ointment compared with vehicle. Significant improvements in the signs and symptoms of atopic dermatitis, percent body surface area affected, and the patient's assessment of pruritus were also observed early in treatment and were maintained throughout the study. Adverse events with a statistically significantly greater incidence in the 0.03% tacrolimus ointment treatment group compared with vehicle were limited to the sensation of skin burning, pruritus, varicella, and vesiculobullous rash (“blisters”). Varicella and vesiculobullous rash occurred at a low incidence (<5%). No adverse event occurred at a statistically higher incidence in the 0.1% tacrolimus ointment-treated group compared with vehicle. Tacrolimus ointment was equally safe for younger (2-6 years) and older (7-15 years) children. Both tacrolimus ointment concentrations (0.03% and 0.1%) were safe and significantly more effective than vehicle for the treatment of atopic dermatitis in children. (J Am Acad Dermatol 2001;44:S47-57.)

Section snippets

Study design

This randomized, double-blind, parallel group, 3-arm, vehicle-controlled study was conducted at 23 centers in the United States between August 1997 and June 1998. Pediatric patients applied either vehicle control (ointment base), 0.03% tacrolimus ointment, or 0.1% tacrolimus ointment. Patients who met entry criteria were randomized with a 1:1:1 allocation ratio and were stratified before randomization by age (≤ 6 years or ≥ 7 years) within each center. The investigator, patient,

Patient disposition and characteristics

A total of 351 patients were enrolled and received at least one dose of randomized study medication; 116 patients received vehicle, 117 received 0.03% tacrolimus ointment, and 118 received 0.1% tacrolimus ointment. A total of 105 patients did not complete the study, the majority (n = 65) of whom were in the vehicle treatment group. Of these vehicle-treated patients, 71% discontinued because of lack of efficacy. The most common reason for discontinuation in either tacrolimus ointment treatment

Discussion

Both concentrations of tacrolimus ointment (0.03% and 0.1%) were demonstrated to be safe and effective for the treatment of moderate to severe atopic dermatitis in children 2 to 15 years of age. Both concentrations of tacrolimus ointment produced substantial clinical improvement and rapidly (generally during the first week of treatment) decreased the amount of affected body surface area while relieving such signs and symptoms as pruritus, edema, erythema, excoriation, lichenification, oozing,

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    Supported by an educational grant from Fujisawa Healthcare, Inc, Deerfield, Illinois

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    This article is part of a supplement sponsored by Fujisawa Healthcare, Inc.

    Dr Paller has received grant support, been a consultant, and has been on the speaker's bureau of Fujisawa Healthcare, Inc. Dr Eichenfeld has received grant/research support and been a consultant for Fujisawa. Dr Leung has received grant/research support from Tanox, Fujisawa Healthcare, and Novartis and has been on the speakers' bureaus of Glaxo and Schering. Dr Stewart has received grant/research support from Fujisawa. Dr Appell has received support via Hill Top Research, Inc.

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    Reprint requests: Amy Paller, MD, Division of Dermatology #107, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614. E-mail: [email protected].

    Additional members of the Tacrolimus Ointment Study Group: Maggie Ayers, Fujisawa Healthcare, Inc, Deerfield, Ill; Mark Boguniewicz, MD, National Jewish Medical and Research Center, Denver, Colo; Debra Breneman, MD, University Dermatology Consultants, Inc, Cincinnati, Ohio; Kevin D. Cooper, MD, University Hospital of Cleveland, Cleveland, Ohio; Loretta Davis, MD, Medical College of Georgia, Augusta, Ga; Lynn Drake, MD, Oklahoma University Health Sciences Center, Oklahoma City, Okla; Jay Erdman, Fujisawa Healthcare, Inc, Deerfield, Ill; Alan Fleischer, MD, Wake Forest University School of Medicine, Winston-Salem, NC; Jon M. Hanifin, MD, Oregon Health Sciences University, Portland, Ore; Ellen Hodosh, PhD, Fujisawa Healthcare, Inc, Deerfield, Ill; Eileen Jaracz, PharmD, Fujisawa Healthcare, Inc, Deerfield, Ill; Teri Kahn, MD, Cleveland Clinic Foundation, Cleveland, Ohio; Sewon Kang, MD, University of Michigan Medical Center, Ann Arbor, Mich; Gerald T. Kilpatrick, MD, Hill Top Research, Inc, West Palm Beach, Fla; Ira D. Lawrence, MD, Fujisawa Healthcare, Inc, Deerfield, Ill; Mark R. Ling, MD, PhD, Emory University (currently at MedaPhase), Atlanta, Ga; Jan M. Logan, Fujisawa Healthcare, Inc, Deerfield, Ill; Anne W. Lucky, MD, Dermatology Research Associates, Cincinnati, Ohio; Rochelle M. Maher, Fujisawa Healthcare, Inc, Deerfield, Ill; Calvin O. McCall, MD, Emory University, Atlanta, Ga; Mamoru Miyake, Fujisawa Healthcare, Inc, Deerfield, Ill; Eugene Monroe, MD, Advanced HealthCare, SC, Milwaukee, Wis; David Pariser, MD, Eastern Virginia Medical School, Norfolk, Va; Linda Pedersen, Fujisawa Healthcare, Inc, Deerfield, Ill; Scott Phillips, MD, University of Chicago, Chicago, Ill; Elyse Rafal, MD, University Medical Center at Stony Brook, Stony Brook, NY; Yoichi Satoi, Fujisawa Healthcare, Inc, Deerfield, Ill; Ronald Savin, MD, Savin Dermatology Center, New Haven, Conn; Lynda C. Schneider, MD, Children's Hospital—Harvard Medical School, Boston, Mass; Daniel Shrager, MD, Fujisawa Healthcare, Inc, Deerfield, Ill; Elaine Siegfried, MD, Saint Louis University Health Sciences Center, St Louis, Mo; Atsushi Tanase, PharmD, Fujisawa Pharmaceutical Ltd, Osaka, Japan; Suzanne Zheng, Fujisawa Healthcare, Inc, Deerfield, Ill.

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    J Am Acad Dermatol 2001;44:S47-57.

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