Efficacy and Safety of Pimecrolimus Cream in the Long-Term Management of Atopic Dermatitis in Children

Abstract

ABSTRACT. Objective. Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD).We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.Methods. Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.Results. Baseline Characteristics of the Patients. The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline.Patient Follow-up and Exposure to Study Medication. The mean duration of follow-up (؎standard error) was 303.7 (؎5.30) days in the pimecrolimus group and 235.2 (؎9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.Efficacy. Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (logrank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators'...

Atopic Dermatitis: Skin-Directed Management

“…Reassuringly, TCIs have been used in children for more than 15 years, there have been no reports of malignancy in children, and there is little to no concern for systemic absorption or systemic immunosuppression. 47 Indeed, in 1 adult study, there was a lower rate of nonmelanoma skin cancer in patients with AD who used TCIs to treat their inflammatory disease. 48 …”

Atopic Dermatitis: an Update and Review of the Literature

“…It is important in ADS treatment with pimecrolimus and tacrolimus according guidelines and recommendation to include optimal skin care, identification of triggers, treatment of infections and avoidance of allergens (35). FDA raised concerns about potential malignancy risk that can be observed with increased concerns for risk for Both agents proved to be effective, with a good safety profile for a treatment period of up to 2 years with pimecrolimus and up to 4 years with tacrolimus (10,37). Current FDA guidelines recommend that topical pimecrolimus nad tacrolimus are indicated for the shortterm or intermittent-long-term treatment of AD in patients 2 years of age or older who are unresponsive to or intolerant of other conventional therapies or in whom there therapies are inadvisable because of potential cancer risk (35).…”

Topical Calcineurin Inhibitors and Malignancy Risk

“…Considering that systemically administered calcineurin inhibitors for graft rejection in organ transplant patients are highly associated with an increased rate of lymphomas, melanomas and non-melanoma skin cancers, theoretically substantial systemic absorption of TCIs could also increase the risk (11). However, there is no evidence that topical use of calcineurin inhibitors leads to systemic immunosuppression considering normal immune response to vaccination, appropriate delayed-type hypersensitivity reaction and no increased incidence of cutaneous and systemic infections in patients treated with TCIs (32)(33)(34)(35). According to pharmacokinetic studies, the systemic absorption rate for both TCIs was very low in more than 99% of the patients presenting with moderate or severe AD including infants and adults making the risk of systemic immunosuppression not biologically plausible.…”