Tacrolimus, a
macrolide immunomodulator, is believed to control
atopic dermatitis by inhibiting T lymphocyte activation, altering cell surface expression on
antigen-presenting dendritic cells and modulating the release of inflammatory mediators from skin mast cells and basophils.
Tacrolimus ointment penetrates human skin with no systemic accumulation after repeated applications; systemic absorption is generally low, with most patients in clinical trials having blood concentrations of the
drug below the limit of quantification. Moderate to severe
atopic dermatitis significantly improved (measured using multiple end-points, including > or = 90% improvement in Physician's Global Evaluation of Clinical Response) with
tacrolimus 0.03 and 0.1%
ointment compared with vehicle in both adult (n = 304 and 328) and pediatric (n = 351) patients in three 12-week, double-blind, randomized, phase III trials. In adults,
tacrolimus ointment was effective
therapy for the treatment of
atopic dermatitis on all skin regions, including the head and neck. The 0.1% concentration was more effective than the 0.03% concentration. Clinical improvement in moderate to severe
atopic dermatitis in adult (n = 316) or pediatric (n = 255) patients was seen as early as week 1, and improvement continued and/or was maintained for up to 6 and/or 12 months in long-term studies. The 0.1% formulation was also effective and well tolerated for up to 2 years.
Tacrolimus 0.03 and 0.1%
ointment was associated with significant quality-of-life benefit in adults, children (aged 5 to 15 years) and toddlers (aged 2 to 4 years) with
atopic dermatitis in 12-week phase III trials (n = 985). Skin burning and
pruritus were the most common application site adverse events in adult and pediatric patients in short-term and long-term trials. These events were generally of short duration and mild or moderate severity. Cutaneous
infections occurred with a similar incidence
after treatment with
tacrolimus ointment to that seen after vehicle in short-term trials.
CONCLUSION: Both short- and long-term monotherapy with
tacrolimus 0.03 and 0.1%
ointment improves moderate to severe
atopic dermatitis in adult and pediatric patients. Topical
tacrolimus ointment is well tolerated, with the majority of adverse events being localized, transient in nature and of mild or moderate severity.
Tacrolimus ointment provides a promising addition to the currently available treatments for
atopic dermatitis; it can be used as a short- or long-term intermittent
therapy for moderate to severe disease, including disease on the head or neck, in adult (0.1 and 0.03% formulations) and pediatric (0.03% formulation) patients who are not adequately responsive to or are intolerant of conventional treatments.