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.
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ABSTRACT: Topical calcineurin inhibitors (TCIs), commercially available since 2000-2001, are the first and only topical medications approved for chronic treatment of atopic dermatitis (AD) in pediatric patients and remain a welcomed alternative to topical corticosteroids. In January 2006, the US Food and Drug Administration (FDA) issued a boxed warning requirement based on a theoretical risk of malignancy (including lymphoma) with TCI use. However, in the years since, analyses of epidemiologic and clinical data have failed to demonstrate a causal relationship between TCI use and malignancy or lymphoma risk, especially for pimecrolimus cream. In fact, the observed number of malignancies and lymphomas observed both in post-marketing surveillance and reported to the FDA using its adverse events reporting system is much lower among TCI-exposed patients than the expected number for the general population. Furthermore, among children enrolled in post-marketing pediatric registry studies for both tacrolimus and pimecrolimus followed for up to 5.5 years [10,724 patient-years (PY)] or 6.5 years (16,219 PY), respectively, the observed number of malignancies and lymphomas is very low and similar to the number expected for a sample of similar size in the general population. In addition to reporting these comparative malignancy and lymphoma data, this article provides a historical overview of the boxed warning requirement and critically evaluates the preclinical, clinical, and epidemiological evidence that has thus far failed to substantiate a relationship between TCI use and malignancy. The authors also provide practical clinical advice for optimizing AD management and patient care in the context of the boxed warning.American Journal of Clinical Dermatology 05/2013; · 2.52 Impact Factor
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ABSTRACT: Topical calcineurin inhibitors (TCI) are a relatively new class of drugs used in dermatology. There are two drug forms available - tacrolimus 0.03% or 0.1% ointment and 1.0% pimecrolimus cream. The drugs act by inhibiting synthesis of proinflammatory cytokines. The only approved indication for using TCI is treatment of atopic dermatitis. The TCI may be used as an alternative therapy to corticosteroids. Tacrolimus is used to treat moderate-to-severe atopic dermatitis, pimecrolimus - mild-to-moderate atopic dermatitis. Topical calcineurin inhibitors do not cause skin atrophy and the drug absorption through the skin is minimal. The TCI have been well-studied, their efficacy was evaluated in a number of vast, long-term studies. The anti-inflammatory potency of tacrolimus ointment is similar to a corticosteroid with moderate activity, while the latter is clearly more active than pimecrolimus cream. Topical calcineurin inhibitors significantly relieve pruritus in atopic eczema.Postepy Dermatologii I Alergologii 06/2013; 30(3):165-169. · 0.66 Impact Factor
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ABSTRACT: Introduction: New knowledge on the pathogenesis of atopic dermatitis (AD) gives us new treatment options. This review emphasizes long-term treatment results. Areas covered: This study includes basic pathogenic factors in AD and presents present and future treatment options. Topical corticosteroids treat the inflammation effectively short term. Topical calcineurin inhibitors (TCIs) show better benefit/risk ratio in long-term treatment. For topical treatment, an effective maintenance treatment results in optimal control of the AD. Of systemic immunosuppressive treatments, efficacy has been shown with azathioprine, ciclosporin, methotrexate and mycophenolate-free sodium. With these compounds, the treatment outcome was ∼ 50% improvement in clinical signs compared with baseline. New treatments under study include systemic compounds, which suppress the T helper type 2 cells. The importance of adherence to treatment is often overlooked, although it has a major impact on treatment outcome. For the present review, PubMed was used as a primary source. Expert opinion: Combination of future TH2-specific systemic treatment with optimal topical treatment with TCI, especially tacrolimus ointment, could help to completely control the skin inflammation in AD. The ultimate goal is to control AD completely, which should help to control the atopic airway disease as well.Expert Opinion on Pharmacotherapy 05/2014; · 2.86 Impact Factor