PRE~ENTED AT THE SYMPOSIUM, "RETINOIDS: PRESENT AND FUTURE," AT THE 18TH WORLD CONGRESS OF. DERMATOLOGY, SUPPORTED BY EDUCATIONAL GRANTS FROM F. HOFFMANN-LA ROCHE LTD AND ROCHE DERMATOLOGICS I
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Topical isotretinoin for photodamaged skin Enrique Sendagorta, MD, a Jeanne Lesiewicz, PhD, b and Robert B. Armstrong, MD b
Strasbourg, France, and Nutley, New Jersey Photodamaged skin is characterized clinically by coarseness, telangiectasia, wrinkling, discrete hyperpigmentedand hypopigmentedmacules, atrophy, and ultimately the development of neoplasms. Studies on the UVB-irradiated hairless mouse indicate that topical application of tretinoin or isotretinoin induces structural modifications at the dermal level. Clinical trials indicate that tretinoin improves skin appearance in patients who have photodamage. This double-blind, vehicle-controlled clinical trial was conducted to determine whether 36 weeks of treatment with topical isotretinoin improves mildly to moderately photodamaged facial skin. After they gave written informed consent 776 patients were randomly assigned to 36 weeks of treatment with either vehicle cream or isotretinoin cream, applied once nightly. Efficacy was evaluated by means of physician and patient assessment and a blinded analysis of standardized photographs taken before and after treatment. When compared with vehicle, treatment with isotretinoin resulted in statistically significant improvement in overall appearance, fine wrinkling, discrete pigmentation, sallowness, and texture. Isotretinoin cream was well tolerated. (J AM ACADDZRMATOL1992;27:S15-S18.)
Photodamage, or chronic actinic damage, denotes changes in appearance and function of the skin that result from long-term sun exposure rather than the passage of time. Photodamaged skin is characterized clinically by coarseness, wrinkling, discrete pigmentation, atrophy, and ultimately premalignant and malignant neoplasms on sun-exposed areas.1 Although photodamaged skin was believed to be irreversibly altered, studies have found that tretinoin (all-trans-retinoic acid) is capable of enhancing the repair of ultraviolet-damaged connective tissue in the hairless mouse. 2 Recent clinical studies have also shown that topically applied tretinoin is an effective treatment of pliotodamage in humans.36 Histologic changes have confirmed the biologic activity of topically applied tretinoin in photodamaged skin. 7 Treatment with tretinoin is associated with local irritation (retinoid dermatitis) in many patients, 4, 5 a factor that may limit its therapeutic usefulness. Our research has been aimed at the identification of other retinoids that may have an improved therapeutic profile for the treatment of photodamaged From the Department of Cfinical Research (Dermatology), Roche International Clinical Research Center, a and Hoffmann-La Roche, Nutley, N.J. b Reprints not available.
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skin. In the UVB-irradiated hairless mouse model, isotretinoin (13-cis-retinoic acid) was active in inducing structural modifications at the dermal level and in wrinkle effacement) This retinoid was well tolerated in toxicologic and clinical tolerability studies. We describe the preliminary results of a large, multicenter clinical study. MATERIAL AND METHODS
A double-blind, randomized, vehicle-controlled, parallel-grouped, multicenter study was conducted. After they gave informed consent 776 patients with mild-to-moderate photodamage were entered into the study at 17 centers in different locations in the United States. Of the total, 67 were men and 709 were women, and they ranged in age from 20 to 76 years (mean, 45 years). Patients were assigned to receive either isotretinoin 0.05% cream for 12 weeks followed by isotretinoin 0.1% cream during the next 24 weeks or vehicle for 36 weeks. Test creams were applied to the entire face nightly, and all patients were instructed to use a sun protection factor 15 sunscreen daily and minimize exposure to sunlight. Efficacy was evaluated by means of a physician's assessment of clinical features (overall skin appearance, fine wrinkles, discrete pigmentation, sallowness, and texture), the patient's self-assessment, and a clinical panel review of photographs. $15
American
S16
Sendagorta et al.
J o u r n a l of the A c a d e m y of
Dermatology
Table I. Physician's clinical assessment at week 36 (change from baseline for clinical skin parameters)* Parameter
Isotretlnoin (n = 307)? mean +_ SE:~
Overall skin appearance Fine wrinkles Discrete pigmentation Sallowness Texture
8.3 _+ 0.55 7.4 + 0.58 5.1 + 0.59 6.2 + 0.50 9.4 __+.0.56
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Vehicle (n = 306)t mean =t=SE~
6.4 5.3 3.6 4.3 7.7
p value
_+ 0.56 _+ 0.57 _ 0.60 __+0.50 +_ 0.57
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Topical isotretinoin for photodamaged skin Enrique Sendagorta, MD, a Jeanne Lesiewicz, PhD, b and Robert B. Armstrong, MD b
Strasbourg, France, and Nutley, New Jersey Photodamaged skin is characterized clinically by coarseness, telangiectasia, wrinkling, discrete hyperpigmentedand hypopigmentedmacules, atrophy, and ultimately the development of neoplasms. Studies on the UVB-irradiated hairless mouse indicate that topical application of tretinoin or isotretinoin induces structural modifications at the dermal level. Clinical trials indicate that tretinoin improves skin appearance in patients who have photodamage. This double-blind, vehicle-controlled clinical trial was conducted to determine whether 36 weeks of treatment with topical isotretinoin improves mildly to moderately photodamaged facial skin. After they gave written informed consent 776 patients were randomly assigned to 36 weeks of treatment with either vehicle cream or isotretinoin cream, applied once nightly. Efficacy was evaluated by means of physician and patient assessment and a blinded analysis of standardized photographs taken before and after treatment. When compared with vehicle, treatment with isotretinoin resulted in statistically significant improvement in overall appearance, fine wrinkling, discrete pigmentation, sallowness, and texture. Isotretinoin cream was well tolerated. (J AM ACADDZRMATOL1992;27:S15-S18.)
Photodamage, or chronic actinic damage, denotes changes in appearance and function of the skin that result from long-term sun exposure rather than the passage of time. Photodamaged skin is characterized clinically by coarseness, wrinkling, discrete pigmentation, atrophy, and ultimately premalignant and malignant neoplasms on sun-exposed areas.1 Although photodamaged skin was believed to be irreversibly altered, studies have found that tretinoin (all-trans-retinoic acid) is capable of enhancing the repair of ultraviolet-damaged connective tissue in the hairless mouse. 2 Recent clinical studies have also shown that topically applied tretinoin is an effective treatment of pliotodamage in humans.36 Histologic changes have confirmed the biologic activity of topically applied tretinoin in photodamaged skin. 7 Treatment with tretinoin is associated with local irritation (retinoid dermatitis) in many patients, 4, 5 a factor that may limit its therapeutic usefulness. Our research has been aimed at the identification of other retinoids that may have an improved therapeutic profile for the treatment of photodamaged From the Department of Cfinical Research (Dermatology), Roche International Clinical Research Center, a and Hoffmann-La Roche, Nutley, N.J. b Reprints not available.
16/0/42347
skin. In the UVB-irradiated hairless mouse model, isotretinoin (13-cis-retinoic acid) was active in inducing structural modifications at the dermal level and in wrinkle effacement) This retinoid was well tolerated in toxicologic and clinical tolerability studies. We describe the preliminary results of a large, multicenter clinical study. MATERIAL AND METHODS
A double-blind, randomized, vehicle-controlled, parallel-grouped, multicenter study was conducted. After they gave informed consent 776 patients with mild-to-moderate photodamage were entered into the study at 17 centers in different locations in the United States. Of the total, 67 were men and 709 were women, and they ranged in age from 20 to 76 years (mean, 45 years). Patients were assigned to receive either isotretinoin 0.05% cream for 12 weeks followed by isotretinoin 0.1% cream during the next 24 weeks or vehicle for 36 weeks. Test creams were applied to the entire face nightly, and all patients were instructed to use a sun protection factor 15 sunscreen daily and minimize exposure to sunlight. Efficacy was evaluated by means of a physician's assessment of clinical features (overall skin appearance, fine wrinkles, discrete pigmentation, sallowness, and texture), the patient's self-assessment, and a clinical panel review of photographs. $15
American
S16
Sendagorta et al.
J o u r n a l of the A c a d e m y of
Dermatology
Table I. Physician's clinical assessment at week 36 (change from baseline for clinical skin parameters)* Parameter
Isotretlnoin (n = 307)? mean +_ SE:~
Overall skin appearance Fine wrinkles Discrete pigmentation Sallowness Texture
8.3 _+ 0.55 7.4 + 0.58 5.1 + 0.59 6.2 + 0.50 9.4 __+.0.56
I I
Vehicle (n = 306)t mean =t=SE~
6.4 5.3 3.6 4.3 7.7
p value
_+ 0.56 _+ 0.57 _ 0.60 __+0.50 +_ 0.57
