The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study.
BACKGROUND
SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases.


OBJECTIVE
In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle.


METHODS
Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone-17-valerate 0.1% cream and triamcinolone acetonide 0.1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology.


RESULTS
Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle. Conclusion The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short-term study demonstrates its potential as long-term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin-folds.
Centre de Pharmacologie Clinique Appliquée à la Dermatologie and Service de Dermatologie, Nice University Hospital, 151 route St Antoine de Ginestière, BP3079 Hôpital de L'Archet II, 06202 Nice cedex 3, Nice, France. cpcad_skinpharma@wanadoo.fr
C
C
Queille-Roussel
C
C
Paul
L
L
Duteil
M C
MC
Lefebvre
G
G
Rapatz
M
M
Zagula
J P
JP
Ortonne
D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D001284:Atrophy / Q000139:chemically induced / Q000000981:diagnostic imaging; D003879:Dermatologic Agents / Q000009:adverse effects*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D008297:Male; D009824:Ointments; D012867:Skin / Q000000981:diagnostic imaging / Q000473:pathology*; D016559:Tacrolimus / Q000009:adverse effects* / Q000031:analogs & derivatives; D014463:Ultrasonography
D000893:Anti-Inflammatory Agents; D003879:Dermatologic Agents; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D009824:Ointments; C117268:pimecrolimus; D016559:Tacrolimus