EFFECTIVENESS OF THE ASCOMYCIN MACROLACTAM SDZ-ASM-981 IN THE TOPICALTREATMENT OF ATOPIC-DERMATITIS

Objective: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a matching placebo cream in the treatment of patients with moderat e atopic dermatitis. Design: A randomized, double-blind, placebo-contr olled, right-and-left comparison study. Setting: Academic referral cen ter. Patients: Thirty-four adult patients with moderate atopic dermati tis. Intervention: Topical 1% SDZ ASM 981 cream was applied twice dail y (n=16) or once daily (n=18) and compared with a corresponding placeb o cream base. Main Outcome Measures: Efficacy was measured using a 4-p oint (0-3) scale for erythema, pruritus, exudation, excoriation, and l ichenification (Atopic Dermatitis Severity Index [ADSI]). The ADSI sco re was defined as the sum of these 5 ratings (range, 0-15) and was det ermined on the pretreatment day (1 to 14 days before day 0) and on day s 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from ba seline (day 0) in the ADSI score was calculated on each of these days. Safety was evaluated by monitoring of adverse events, physical examin ation, hematologic examination, clinical chemistry studies, urinalysis , and measurement of blood levels of SDZ ASM 981. Results: Of the 38 p atients recruited, 34 started and 28 completed treatment according to the protocol. Sixteen patients used the cream twice daily, with signif icant improvement after 2 days of treatment. Within 3 weeks of topical therapy with 1% SDZ ASM 981 cream twice daily, a mean reduction of 71 .9% in the ADSI score was observed at the actively treated test sites compared with a mean reduction of 10.3% at the placebo-treated test si tes (P<.001). Efficacy was significantly less in the group treated onc e daily (n=18),with mean reductions of 37.7% and 6.2%, respectively. T he efficacy was especially apparent for pruritus and excoriation. Ther e were no clinically relevant drug-related adverse effects. Conclusion s: Treatment with 1% SDZ ASM 981 cream was well tolerated. Twice-daily application of 1% SDZ ASM 981 cream was significantly more effective than use of the corresponding placebo and more effective than once-dai ly treatment. The new macrolactam ascomycin derivative SDZ ASM 981 is a promising agent for the treatment of patients with atopic dermatitis . More elaborate phase 2 and 3 trials are under way to fully investiga te the potential of this medication.