Question

• A 40-year-old male brings his two sons to see you in clinic, ages 6 and 7 with moderately severe eczema. Both have had moderately successful courses with corticosteroids in the past, but he wants to know if there is any other treatment you would prescribe for his sons. In children with moderately severe eczema, is topical tacrolimus more effective than steroids?

Clinical Bottom Lines

1. Topical tacrolimus applied twice daily resulted in excellent (70%) improvement in atopic dermatitis in children ages 7 to 16.
2. No serious adverse advents were noted.
3. Topical tacrolimus appears to be safe for short-term use.
4. Other studies have demonstrated long-term safety in adults, but such studies are still ongoing in children.
5. NNT for an observed response: 3 patients for two weeks.

Summary of Key Evidence

1. 180 children between the ages of 7 and 16 with 5 to 30 % body surface area involvement of atopic dermatitis were randomized to receive twice a day applications of either tacrolimus ointment at 1 of 3 concentrations-0.03 % (n=43), 0.1% ( n=49), 0.3% (n=44), or vehicle (propylene carbonate, white wax, mineral oil, and petrolatum) for 22 days with a two week follow up period.1
2. Patients had to stop topical corticosteroids for one week, and systemic corticosteroids for six weeks. Patients receiving immunotherapy or phototherapy had to stop at least one month before enrollment.
3. Patients were randomized to one of the four treatment arms. The study was blinded-all tubes of medication looked the same.
4. Eighteen of the 180 patients discontinued treatment early; 7 in the vehicle group, 2 in 0.03% tacrolimus group, 5 in the 0.1% group, and 4 in the 0.3 % group. 4 of the 7 patients in the vehicle group and one patient in the tacrolimus group discontinued treatment because of perceived lack of efficacy, 2 of 44 and 5 of 136 discontinued treatment because of adverse events and noncompliance accounted for 1 patient in the vehicle group and 5 in the tacrolimus groups.
5. Outcomes were assessed by the Physicians' Global evaluation of clinical response, modified Eczema Severity Index, Head and Neck Total Score, and patient's assessment to overall treatment.
6. Blood levels monitored on days 0, 4 and 22. Highest level noted was 2.66 ng/ml, most under 1 ng/ml.
7. Using the Physicians' Global Evaluation of Clinical Response (greater than 75 % improvement), 69% CI 53-82% (0.03%), 67% CI 52-81% (0.1%), 70% CI 54-83% (0.3%), and 38% CI 24-54 (vehicle) reported a response. Estimating the control event rate at 62% (those that did not see a response in the vehicle group), the EER is 30%, the RRR 52% with a ARR of 32% and NNT of 3.

Additional Comments

• Tacrolimus is thought to act by penetrating cells, binding to cellular proteins (FK-binding proteins) which block the action of calcineurin, which in turn results in a suppression of cytokine gene transcription.
• Atopic dermatitis is the most common chronic skin condition in children--10% of the pediatric age population have it.
• Tacrolimus is less than 0.5% systemically absorbed
• Most of the adverse effects (burning) were described at the beginning of therapy with denuded skin. There were no systemic adverse events.
• The youngest participant in this study was 7 years old. We don't know how this would work for younger children.
• While the price of topical tacrolimus has not been set, it will likely be expensive compared with steroid treatments.

Citation

1. Boguniewicz et al. A randomized, vehicle controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Journal of Allergy & Clinical Immunology 1998; 102: 637-44.
2. Fleischer AB Jr. Treatment of atopic dermatitis: role of tacrolimus ointment as a topical noncorticosteroid therapy. Journal of Allergy & Clinical Immunology 1999; 104: S126-30.
3. Ruzicka T et al. A short-term trial of tacrolimus ointment for atopic dermatitis. NEJM 1997; 337(12): 812-21.

CAT Author: Megan Spohr, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: March 5, 2001