Tacrolimus shown better than topical steroids
"Clear/almost clear" results seen in patients with atopic dermatitis
A topic dermatitis affects adults and as much as 20 percent of school-age children. Aside from significant functional impairment and social stigma, it also brings increased risk for bacterial and viral infections, as well as asthma.
Because of problems associated with use of topical steroids, treatment of atopic dermatitis has shifted focus to nonsteroidal topical options. One of these is tacrolimus (Protopic), the first in a new class of nonsteroidal, topical calcineurin inhibitors (TCIs) developed for patients with moderate to severe atopic dermatitis.
Dr. Mary Joyce Rico, associate professor of clinical dermatology at Northwestern University, discussed this treatment option in a forum organized by Janssen Pharmaceutica in March.
The worldwide clinical-development program for tacrolimus, which was launched in Japan in 1999, involved over 19,000 patients, including 7,600 children. "Since [its approval] in the US in 2000, 1.7 million patients have already been treated, which provide a very robust database," said Rico.
Tacrolimus over corticosteroids
Among the studies were two pediatric randomized, double-blind studies (Soter N, et al. J Am Acad Dermatol 2001; Paller A, et al. J Am Acad Dermatol 2001) that compared tacrolimus versus hydrocortisone (HC) acetate. Conducted over three weeks, the treatment regimen involved tacrolimus 0.03 percent and 0.1 percent against HC acetate ointment one percent. Results revealed that tacrolimus 0.03 percent and 0.1 percent were both more effective than hydrocortisone (p < 0.001). The study also demonstrated that the 0.1-percent preparation was more effective than 0.03 percent in children.
Meanwhile, Antaya et al., in three separate but related randomized, double-blind multicenter studies involving 1,065 pediatric and adult patients (Proceedings of the Society for Pediatric Dermatology, June 2004) also showed tacrolimus ointment to be more effective than pimecrolimus cream, also a TCI. In the first week, tacrolimus produced "clear/almost clear" results in a slightly higher number of patients. But by the third week, tacrolimus showed far greater treatment success, with significant reductions in eczema area and severity index (EASI); percent body surface area (% BSA) affected, and patient's assessment of pruritus.
Since pimecrolimus may be indicated for patients with mild to moderate disease while tacrolimus is effective for moderate to severe disease, the overlap for moderate disease was also investigated. Results showed significant advantage in efficacy by tacrolimus over pimecrolimus from the third week onwards. Tacrolimus was also significantly more effective in stopping itchiness than pimecrolimus.
As for adverse events, no statistically significant difference was seen in the rate of incidence of burning, erythema, site pain, pruritus, and infection in both treatment arms. Application-site events usually occurred early and were associated with either concentration of tacrolimus. However, these were relatively minor and rarely resulted in discontinuation of treatment (under two percent of pediatric patients, under five percent of adults). Observed Rico: "In general, adverse events were less commonly reported in the pediatric patients. [Whether] the kids don't complain as much or just a little bit more tolerant of the product was hard to tell." These events usually did not last long, and tended to resolve while the skin healed.
One of the concerns in using topical medications is the degree of absorption from the site, giving rise to systemic blood levels of the drug. But evaluation in over 19,000 patients showed that tacrolimus levels in the blood were low (< 0.5 ng/ml) and usually transient, occurring early in treatment, reported Rico.
Longest, largest studies
To determine the effects of long-term tacrolimus monotherapy, 800 patients were treated for up to four years (the Longest Study) while 8,000 were treated for two years (the Largest Study). Most patients in both studies were actually treated with 0.1-percent ointment because the higher concentration was expected to provide the greater information about long-term exposure (Hanifin JM, et al. J Am Acad Dermatol. In press).
In the Longest Study, relief of symptoms was observed within one week of topical tacrolimus application. Significant improvements were also observed through the end of the study (80-percent decrease in EASI, 78-percent decrease in %BSA), while clinical improvement was maintained over three years. No evidence of tachyphylaxis was noted. The Largest Study recorded dramatic reductions in %BSA after the first and sixth months of therapy. The effect reached a plateau over time, but there was still some measure of improvement.
Summing up, Rico said Protopic is a safe, novel, and effective treatment for patients with atopic dermatitis. "It is an important addition to our therapeutic armamentarium and there is extensive clinical and postmarketing experience that demonstrates there is no increased risk for systemic infection or malignancy."
|
