Effectiveness of the ascomycin macrolactam SDZ ASM 981 in the
topical treatment of atopic dermatitis.
Van Leent EJ, Graber M, Thurston M, Wagenaar A, Spuls PI, Bos JD.
Department of Dermatology, Academic Medical Center, University of Amsterdam, The
Netherlands.
OBJECTIVE: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a
matching placebo cream in the treatment of patients with moderate atopic
dermatitis. DESIGN: A randomized, double-blind, placebo-controlled,
right-and-left comparison study. SETTING: Academic referral center. PATIENTS:
Thirty-four adult patients with moderate atopic dermatitis. INTERVENTION:
Topical 1% SDZ ASM 981 cream was applied twice daily (n=16) or once daily (n=18)
and compared with a corresponding placebo cream base. MAIN OUTCOME MEASURES:
Efficacy was measured using a 4-point (0-3) scale for erythema, pruritus,
exudation, excoriation, and lichenification (Atopic Dermatitis Severity Index [ADSI]).
The ADSI score was defined as the sum of these 5 ratings (range, 0-15) and was
determined on the pretreatment day (1 to 14 days before day 0) and on days 0, 2,
4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from baseline (day 0) in
the ADSI score was calculated on each of these days. Safety was evaluated by
monitoring of adverse events, physical examination, hematologic examination,
clinical chemistry studies, urinalysis, and measurement of blood levels of SDZ
ASM 981. RESULTS: Of the 38 patients recruited, 34 started and 28 completed
treatment according to the protocol. Sixteen patients used the cream twice
daily, with significant 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 sites (P<.001). Efficacy
was significantly less in the group treated once daily (n=18), with mean
reductions of 37.7% and 6.2%, respectively. The efficacy was especially apparent
for pruritus and excoriation. There were no clinically relevant drug-related
adverse effects. CONCLUSIONS: 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-daily 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 investigate the potential
of this medication.
