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

Authors

  • C. Queille-Roussel,

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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  • C. Paul,

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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  • L. Duteil,

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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  • M-C. Lefebvre,

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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  • G. Rapatz,

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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  • M. Zagula,

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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  • J-P. Ortonne

    1. 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
      *Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland
      †Novartis Pharma SA, Rueil-Malmaison, France
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Dr Catherine Queille-Roussel. E-mail: cpcad_skinpharma@wanadoo.fr

Abstract

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.

Objectives  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.

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