Long-term efficacy and tolerability of tacrolimus 0.03% ointment in infants:* a two-year open-label study.
ABSTRACT Tacrolimus ointment is effective for treatment of moderate to severe atopic dermatitis (AD) in children aged ≥2 years (Br J Dermatol, 2004; 150: 554). Here, efficacy and tolerability of tacrolimus 0.03% ointment were evaluated in 50 infants aged <2 years at start of treatment.
Infants with AD previously enrolled in a tacrolimus ointment pharmacokinetics trial were eligible for a 24-month open-label phase II study. Tacrolimus 0.03% ointment was applied to affected areas until clearance. In cases of exacerbation or clinical worsening, patients restarted treatment.
Mean ± SD Eczema Area and Severity Index (EASI) score improved, from 11.2 ± 10.5 baseline to 2.6 ± 4.1 at endpoint (24 months); mean affected body surface area decreased from 25.2 ± 21.1% to 5.1 ± 9.0%, with improvement on all items of the Physicians' Assessment of Individual Signs. The Physicians' Global Evaluation of Clinical Response showed a result of "cleared"/"excellent" for 63.3% of patients; 85.7% of parents/guardians assessed symptoms as "much better." Treatment was well tolerated, with common, nonserious respiratory infections and gastroenteritis the most frequently reported adverse events. The most common application-site events were infections and pruritus. Over 98% of blood samples showed tacrolimus concentrations <1.0 ng/ml; >40% showed concentrations below the lower limit of quantification (0.0250 ng/ml).
Over a period of two years, tacrolimus 0.03% ointment was associated with substantial clinical improvement of AD in infants aged <2 years. Treatment tolerability was similar to that seen in older children.
- [show abstract] [hide abstract]
ABSTRACT: Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes. 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.British Journal of Dermatology 03/2004; 150(3):554-62. · 3.76 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The systemic exposure to tacrolimus after first and repeated application of 0.1% tacrolimus ointment was investigated in 32 adults with moderate to severe atopic dermatitis. Patients were allocated to treatment groups according to the size of the affected area to be treated: Group 1</=3000 cm(2) (N=11); Group 2>3000 cm(2)</=6000 cm(2) (N=12); Group 3>6000 cm(2)</=10,000 cm(2) (N=9). Ointment was applied twice daily for 13 d and once daily on Day 14; the size of application area remained the same irrespective of healing. Blood samples were collected on Days 1 (first application), 4, and 14 (last application) and analyzed by a validated HPLC-MS/MS method. Systemic exposure to tacrolimus was generally low with 96% of blood samples assayed containing concentrations below 1 ng per mL and 23% of samples below the lower limit of quantification (0.025 ng per mL). Peak concentrations after first ointment application were </=2.8 ng per mL, and the mean area under the concentration-time curve between 0 and 12 h using the trapezoidal rule (AUC(0-12)) values were 1.1, 1.6, and 4.8 ng h per mL for Groups 1, 2, and 3, respectively. The corresponding mean values on Day 14 were similar indicating negligible systemic accumulation of tacrolimus after repeated ointment applications. Both the rate and extent of topical absorption decreased as the skin lesions healed.Journal of Investigative Dermatology 07/2005; 125(1):68-71. · 6.19 Impact Factor
- [show abstract] [hide abstract]
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.Journal of the American Academy of Dermatology 01/2001; 44(1 Suppl):S47-57. · 4.91 Impact Factor