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Multicenter trial for long-term safety and efficacy comparison of 0.05% desonide and 1% hydrocortisone ointments in the treatment of atopic dermatitis in pediatric patients
Multicenter trial for long-term safety and efficacy comparison of 0.05% desonide and 1% hydrocortisone ointments in the treatment of atopic dermatitis in pediatric patients Joseph Jorizzo, MD, a Moise Levy, MD, b Anne Lucky, MD, c Joel Shavin, MD, d Gerald Goldberg, MD, e Frank Dunlap, MD, e Ann Hinds, PA, a Laura Strelka, RN, a Michael Baker, BS, f Michael Tuley, PhD, f and Janusz M. Czernielewski, M D f
Winston-Salem, North Carolina; Houston and Fort Worth, Texas; Cincinnati, Ohio; Snellville, Georgia; and Tucson, Arizona
Background:Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children. Objective:Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopie dermatitis. Methods: One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration. Results: No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment (p < 0.05). Conclusion: Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months. (J AM ACADDERMATOL1995;33:74-7.)
Desonide is a topical, nonfluorinated, class 6 steroid that is effective in treating pruritic eczematous diseases.I, 2 Desonide cream has demonstrated a good safety and efficacy profile during the many years (since the early 1970s) it has been used. 3-9 Ointments are generally preferred for patients with atopic dermatitis, in part because of their lubricating effect and the simplicity of the formulation (i.e.,
ointments have significantly fewer ingredients and generally no preservatives). Hydrocortisone in a concentration up to 1% is a nonprescription product and is generally considered to be the mildest of the topical corticosteroids. The purpose of this study was to compare 0.05% desonide ointment with 1.0% hydrocortisone ointment in the treatment of children with atopic dermatitis. MATERIAL AND METHODS
From The Bowman Gray School of Medicine, Winston-Salema; Baylor College of Medicine, Texas Children's Hospital, Houstonb; Dermatology Research Associates, CincinnatiC; Gwinnett Clinical Research Center, Snellvillea;Argus Research, Tucsone; and Galderrna Laboratories Inc., Fort Worth. f Reprint requests: Michael D. Baker, BS, P.O. Box 331329, Fort Worth, TX 76163. Copyright © 1995 by the American Academy of Dermatology, Inc. 0190-9622/95 $3.00 + 0 16/1/62389
74
Both ointments were formulated in similar bases: 0.05% desonide in polyethylene and mineral oil and 1.0% hydrocortisone in mineral oil, petrolatum, and sorbitan sesqueoleate (a nonionic emulsifier). This study was a multicenter, randomized, investigator-masked, parallel-group design that included children up to and including 12 years of age. Before initiation of the study, each patient and guardian or parent was corn-
Journal of the American Academy of Dermatology Volume 33, Number 1
Jorizzo et al.
68
70
75
69
60 50 41 40 30 20 10 0 Week 1
Week 3
Week 5
EndPoint
i_Uyes?r~ ide .IJ'-7 ,ydr°cor tls°neI Fig. 1. Percentageofpatientswhohadclearingormarkedimprovementateachevaluation. Asterisk, Chi-square test, p < 0.05.
pletely informed about pertinent details and purpose of the study. A written informed consent was signed by both the patient, depending on age, and the guardian or parent. Patients were not to use any interfering topical medication for 14 days, systemic antihistamines for 7 days, or systemic corticosteroids for 30 days before the start of the study but could use emollients during this period. However, the physician could enter a patient into the study before the end of the washout period, if the patient had worsening pruritus that required treatment. Study treatments were to be applied twice daily. Compliance was monitored by examination of the returned tubes for approximate use, and all tubes were weighed on return to the sponsor. In addition, parents were provided a diary to record any missed doses. Patients were provided with a nonmedicated cleansing bar (Cetaphil). Shampoos, sunscreens, and emollients were left to the parents' choice. At each follow-up evaluation (weeks 1,3, and5, and monthly visits at months 2 to 6), the patient's response to treatment was assessed. Specific lesions were selected for evaluation, but the patients were allowed to apply the medications to all areas of involvement. Signs of atrophy9 were evaluated with an 8x magnifying lamp. Subjective evaluations of stinging and burning were recorded. Efficacy was determined by objective evaluation of global improvement, erythema, lichenification, excoriations, oozing and crusting, and induration ~nd pap~ules. The patients, guardians, or parents subjectively assessed pruritus. Each safety and efficacy feature was ranked on a scale of 0 through 3 (0 = none, 1 = mild, 2 = moderate, and 3 = severe). Patients were required to have a sum of the scores of 5 or higher to qualify for entry into the study. The primary efficacy variable was the physician's overall global assessment of improvement compared with
Table I. Patient distribution according to age range and treatment Distribution ( % ) 5-wk study (n = 113)
I
Age range J (yr)
Up to 3 4-6 7-9 10-12
20-wk extension
(n = 3o3
Desonide Hydrocortisone Desonifle Hydrocortisone
47.4 21.1 15.8 15.8
39.3 30.4 19.6 10.7
43.8 25 6.3 25
25 30 30 15
baseline assessment. This assessment was categorized as follows: clear, 100% clearing except for residual discoloration; marked improvement, 50% to 74% clearing; slight improvement, less than 50% clearing; no change; and exacerbation. The global assessment of improvement was summarized by treatment and category at each evaluation. The proportion of patients receiving each treatment regimen who had had clearing or marked improvement from baseline was tested for significant differences with a chisquare test. Other efficacy variables were also summarized by treatment and category at each evaluation time and end point (Table I). The proportion of patients who had no signs or symptoms at each visit was tested for significance between treatment groups with a chi-square test. The mean change from baseline at each evaluation time and end point was computed and tested for significant treatment, investigator, and treatment-by-investigator interaction with a two-way analysis of variance. The
76
Journal of the American Academy of Dermatology July 1995
Jorizzo et al.
O
=.
Baseline
Week 1
Week 3
i Desonide
Week 5
Endpoint
[ ] Hydrocortisone 1
Fig. 2. Mean summary score (sum of erythema, lichenification, excoriations, oozing or crusting, induration, and pruritus scores, each of which was scored as 0 to 3) at each visit. Asterisk, Analysis of variance, p < 0.05. Table II. Patients without signs or symptoms at end point (last observation) No. (%) of patients Hydrocortisone 1%
Between-lreatment comparison (/, Value)
19 (33.9) 25 (44.6) 32 (57.1) 34 (60.7) 25 (44.6) 22 (39.3)
<0.05 NS <0.05 <0.05 NS <0.05
I
Desonide0.05%
I i
Erythema Lichenification Excoriations Oozing/crusting Induration/papules Pruritus
29 (52.7) 27 (49.1) 42 (76.4) 43 (78.2) 33 (60.0) 32 (58.2)
NS, Not significant.
summary scores (sum of the individual rank scores of all efficacy variables) were analyzed in the same way as the individual features. The safety variables were compared with two-sided nonparametric methods. RESULTS A total of 113 patients, 62 girls and 51 boys, were enrolled at five centers. Fifty-seven patients were randomly assigned to receive desonide ointment and 56 to receive hydrocortisone ointment. The patients' ages ranged from 10 months to 12 years (mean age, 4.8 years). The majority of patients (90) completed 5 weeks of treatment, and, of those, 36 (16 receiving desonide and 20 hydrocortisone) chose to continue treatment for up to an additional 20 weeks (Table I). Each patient applied approximately 4 gm of ointment each treatment day. Of the 113 patients, 111 were assessable for efficacy. Two patients were in the desonide group with no follow-up data. A baseline comparison of demo-
graphics and disease severity revealed no significant differences between treatment groups at the start of the study. Neither treatment produced signs of atrophy, and any stinging or burning sensation that occurred was slight. By week 1 physician's global assessment revealed that the percentage of patients in the desonide group who had cleared or marked improvement (36%) was significantly (p = 0.05) greater than that of those in the hydrocortisone group (20%). Improvement continued throughout the study with both treatments. End-point analysis, which is the last observation made, shows that the difference between treatments is highly significant (p = 0.003), with 69% in the desonide group showing clearing or marked improvement compared with 41% in the hydrocortisone group during the first 5 weeks of treatment (Fig. 1). Analysis of the week 1 data revealed that des-
Journal of the American Academy of Dermatology Volume 33, Number 1
onide-treated patients had significantly (p < 0.05) more rapid improvement of erythema and induration than patients treated with hydrocortisone ointment. Desonide demonstrated greater improvement of erythema, oozing and crusting, excoriations, and pruritus. A significantly greater number of patients treated with desonide were without these signs and symptoms at end point (Table II). When the efficacy summary scores were analyzed, patients treated with desonide ointment showed a significantly (p < 0.05) better improvement at both week 1 and end point for mean improvementfrom baseline (Fig. 2). Likewise, in the percentage of patients who had improvementin their summary scores of less than the minimum entry criterion of 5, the difference was significantly better (p < 0.05) at week 1 and at end point for patients in the desonide group. Both treatment groups continued to improve during the extended portion of the study. The desonide group included a significantly greater percentage (83% vs 33% p < 0.05) of patients who cleared or had marked improvement through 3 months. From month 3 through month 6 the improvement for both treatment groups leveled off and there was no significant difference in the overall severity rating in the two groups. DISCUSSION Both ointments were found to be safe and effective in treating atopic dermatitis, but the investiga-
Jorizzo et aL
77
tor's global assessment of improvement in disease severity was significantly better (p < 0.05) for desonide at all evaluations and at end point. There were no reports of atrophy in either treatment group at the 6-month evaluation. We conclude that both ointments were safe and effective in treating atopic dermatitis in children. However, 0.05% desonide ointment demonstrated better efficacy and had a topical safety profile equal to 1.0% hydrocortisone ointment. REFERENCES
1. Lucky AW. Principles of the use of glucocorticosteroids in the growing child. Pediatr Dermatol 1984;3:226-35. 2. Barsky S. Clinical comparison of desonide cream with fluocinonide cream in steroid-responsive dermatological disorders. Cutis 1976;18:826-30. 3. Bluefarb SM. Clinical comparison of desonide with betamethasone valerate cream: a double-blind randomized study. Int J Dermatol 1972;11:73-6. 4. Cornell RC, Stoughton RB. The use of topical steroids in psoriasis. Dermatol Clin 1984;2:397-409. 5. Donsky HJ. A comparative double-blind randomized clinical study of a new nonfluorinated topical corticosteroid. Cutis 1972;9:46-8. 6. Gentry WC, Rosenberg EW, Goltz RW. A clinical evaluation of 0.05% desonide cream. Arch Dermatol 1973; 107:870-1. 7. Reque PG. The treatment of common dermatoses with topically applied 0.05% desonide cream. J Med Assoc Ala 1972;42:1:25-7. 8. Smith EB, Gregory JF, Bartruff JK. Desonide: a potent nonfluorinated topical steroid, vasoconstriction assay, and clinical trial. South Med J 1972;66:325-8. 9. Henrijean A, Lapiere CM. Clinical evaluation of desonide cream. Curr Ther Res 1983;33:775-81.
Winston-Salem, North Carolina; Houston and Fort Worth, Texas; Cincinnati, Ohio; Snellville, Georgia; and Tucson, Arizona
Background:Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children. Objective:Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopie dermatitis. Methods: One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration. Results: No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment (p < 0.05). Conclusion: Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months. (J AM ACADDERMATOL1995;33:74-7.)
Desonide is a topical, nonfluorinated, class 6 steroid that is effective in treating pruritic eczematous diseases.I, 2 Desonide cream has demonstrated a good safety and efficacy profile during the many years (since the early 1970s) it has been used. 3-9 Ointments are generally preferred for patients with atopic dermatitis, in part because of their lubricating effect and the simplicity of the formulation (i.e.,
ointments have significantly fewer ingredients and generally no preservatives). Hydrocortisone in a concentration up to 1% is a nonprescription product and is generally considered to be the mildest of the topical corticosteroids. The purpose of this study was to compare 0.05% desonide ointment with 1.0% hydrocortisone ointment in the treatment of children with atopic dermatitis. MATERIAL AND METHODS
From The Bowman Gray School of Medicine, Winston-Salema; Baylor College of Medicine, Texas Children's Hospital, Houstonb; Dermatology Research Associates, CincinnatiC; Gwinnett Clinical Research Center, Snellvillea;Argus Research, Tucsone; and Galderrna Laboratories Inc., Fort Worth. f Reprint requests: Michael D. Baker, BS, P.O. Box 331329, Fort Worth, TX 76163. Copyright © 1995 by the American Academy of Dermatology, Inc. 0190-9622/95 $3.00 + 0 16/1/62389
74
Both ointments were formulated in similar bases: 0.05% desonide in polyethylene and mineral oil and 1.0% hydrocortisone in mineral oil, petrolatum, and sorbitan sesqueoleate (a nonionic emulsifier). This study was a multicenter, randomized, investigator-masked, parallel-group design that included children up to and including 12 years of age. Before initiation of the study, each patient and guardian or parent was corn-
Journal of the American Academy of Dermatology Volume 33, Number 1
Jorizzo et al.
68
70
75
69
60 50 41 40 30 20 10 0 Week 1
Week 3
Week 5
EndPoint
i_Uyes?r~ ide .IJ'-7 ,ydr°cor tls°neI Fig. 1. Percentageofpatientswhohadclearingormarkedimprovementateachevaluation. Asterisk, Chi-square test, p < 0.05.
pletely informed about pertinent details and purpose of the study. A written informed consent was signed by both the patient, depending on age, and the guardian or parent. Patients were not to use any interfering topical medication for 14 days, systemic antihistamines for 7 days, or systemic corticosteroids for 30 days before the start of the study but could use emollients during this period. However, the physician could enter a patient into the study before the end of the washout period, if the patient had worsening pruritus that required treatment. Study treatments were to be applied twice daily. Compliance was monitored by examination of the returned tubes for approximate use, and all tubes were weighed on return to the sponsor. In addition, parents were provided a diary to record any missed doses. Patients were provided with a nonmedicated cleansing bar (Cetaphil). Shampoos, sunscreens, and emollients were left to the parents' choice. At each follow-up evaluation (weeks 1,3, and5, and monthly visits at months 2 to 6), the patient's response to treatment was assessed. Specific lesions were selected for evaluation, but the patients were allowed to apply the medications to all areas of involvement. Signs of atrophy9 were evaluated with an 8x magnifying lamp. Subjective evaluations of stinging and burning were recorded. Efficacy was determined by objective evaluation of global improvement, erythema, lichenification, excoriations, oozing and crusting, and induration ~nd pap~ules. The patients, guardians, or parents subjectively assessed pruritus. Each safety and efficacy feature was ranked on a scale of 0 through 3 (0 = none, 1 = mild, 2 = moderate, and 3 = severe). Patients were required to have a sum of the scores of 5 or higher to qualify for entry into the study. The primary efficacy variable was the physician's overall global assessment of improvement compared with
Table I. Patient distribution according to age range and treatment Distribution ( % ) 5-wk study (n = 113)
I
Age range J (yr)
Up to 3 4-6 7-9 10-12
20-wk extension
(n = 3o3
Desonide Hydrocortisone Desonifle Hydrocortisone
47.4 21.1 15.8 15.8
39.3 30.4 19.6 10.7
43.8 25 6.3 25
25 30 30 15
baseline assessment. This assessment was categorized as follows: clear, 100% clearing except for residual discoloration; marked improvement, 50% to 74% clearing; slight improvement, less than 50% clearing; no change; and exacerbation. The global assessment of improvement was summarized by treatment and category at each evaluation. The proportion of patients receiving each treatment regimen who had had clearing or marked improvement from baseline was tested for significant differences with a chisquare test. Other efficacy variables were also summarized by treatment and category at each evaluation time and end point (Table I). The proportion of patients who had no signs or symptoms at each visit was tested for significance between treatment groups with a chi-square test. The mean change from baseline at each evaluation time and end point was computed and tested for significant treatment, investigator, and treatment-by-investigator interaction with a two-way analysis of variance. The
76
Journal of the American Academy of Dermatology July 1995
Jorizzo et al.
O
=.
Baseline
Week 1
Week 3
i Desonide
Week 5
Endpoint
[ ] Hydrocortisone 1
Fig. 2. Mean summary score (sum of erythema, lichenification, excoriations, oozing or crusting, induration, and pruritus scores, each of which was scored as 0 to 3) at each visit. Asterisk, Analysis of variance, p < 0.05. Table II. Patients without signs or symptoms at end point (last observation) No. (%) of patients Hydrocortisone 1%
Between-lreatment comparison (/, Value)
19 (33.9) 25 (44.6) 32 (57.1) 34 (60.7) 25 (44.6) 22 (39.3)
<0.05 NS <0.05 <0.05 NS <0.05
I
Desonide0.05%
I i
Erythema Lichenification Excoriations Oozing/crusting Induration/papules Pruritus
29 (52.7) 27 (49.1) 42 (76.4) 43 (78.2) 33 (60.0) 32 (58.2)
NS, Not significant.
summary scores (sum of the individual rank scores of all efficacy variables) were analyzed in the same way as the individual features. The safety variables were compared with two-sided nonparametric methods. RESULTS A total of 113 patients, 62 girls and 51 boys, were enrolled at five centers. Fifty-seven patients were randomly assigned to receive desonide ointment and 56 to receive hydrocortisone ointment. The patients' ages ranged from 10 months to 12 years (mean age, 4.8 years). The majority of patients (90) completed 5 weeks of treatment, and, of those, 36 (16 receiving desonide and 20 hydrocortisone) chose to continue treatment for up to an additional 20 weeks (Table I). Each patient applied approximately 4 gm of ointment each treatment day. Of the 113 patients, 111 were assessable for efficacy. Two patients were in the desonide group with no follow-up data. A baseline comparison of demo-
graphics and disease severity revealed no significant differences between treatment groups at the start of the study. Neither treatment produced signs of atrophy, and any stinging or burning sensation that occurred was slight. By week 1 physician's global assessment revealed that the percentage of patients in the desonide group who had cleared or marked improvement (36%) was significantly (p = 0.05) greater than that of those in the hydrocortisone group (20%). Improvement continued throughout the study with both treatments. End-point analysis, which is the last observation made, shows that the difference between treatments is highly significant (p = 0.003), with 69% in the desonide group showing clearing or marked improvement compared with 41% in the hydrocortisone group during the first 5 weeks of treatment (Fig. 1). Analysis of the week 1 data revealed that des-
Journal of the American Academy of Dermatology Volume 33, Number 1
onide-treated patients had significantly (p < 0.05) more rapid improvement of erythema and induration than patients treated with hydrocortisone ointment. Desonide demonstrated greater improvement of erythema, oozing and crusting, excoriations, and pruritus. A significantly greater number of patients treated with desonide were without these signs and symptoms at end point (Table II). When the efficacy summary scores were analyzed, patients treated with desonide ointment showed a significantly (p < 0.05) better improvement at both week 1 and end point for mean improvementfrom baseline (Fig. 2). Likewise, in the percentage of patients who had improvementin their summary scores of less than the minimum entry criterion of 5, the difference was significantly better (p < 0.05) at week 1 and at end point for patients in the desonide group. Both treatment groups continued to improve during the extended portion of the study. The desonide group included a significantly greater percentage (83% vs 33% p < 0.05) of patients who cleared or had marked improvement through 3 months. From month 3 through month 6 the improvement for both treatment groups leveled off and there was no significant difference in the overall severity rating in the two groups. DISCUSSION Both ointments were found to be safe and effective in treating atopic dermatitis, but the investiga-
Jorizzo et aL
77
tor's global assessment of improvement in disease severity was significantly better (p < 0.05) for desonide at all evaluations and at end point. There were no reports of atrophy in either treatment group at the 6-month evaluation. We conclude that both ointments were safe and effective in treating atopic dermatitis in children. However, 0.05% desonide ointment demonstrated better efficacy and had a topical safety profile equal to 1.0% hydrocortisone ointment. REFERENCES
1. Lucky AW. Principles of the use of glucocorticosteroids in the growing child. Pediatr Dermatol 1984;3:226-35. 2. Barsky S. Clinical comparison of desonide cream with fluocinonide cream in steroid-responsive dermatological disorders. Cutis 1976;18:826-30. 3. Bluefarb SM. Clinical comparison of desonide with betamethasone valerate cream: a double-blind randomized study. Int J Dermatol 1972;11:73-6. 4. Cornell RC, Stoughton RB. The use of topical steroids in psoriasis. Dermatol Clin 1984;2:397-409. 5. Donsky HJ. A comparative double-blind randomized clinical study of a new nonfluorinated topical corticosteroid. Cutis 1972;9:46-8. 6. Gentry WC, Rosenberg EW, Goltz RW. A clinical evaluation of 0.05% desonide cream. Arch Dermatol 1973; 107:870-1. 7. Reque PG. The treatment of common dermatoses with topically applied 0.05% desonide cream. J Med Assoc Ala 1972;42:1:25-7. 8. Smith EB, Gregory JF, Bartruff JK. Desonide: a potent nonfluorinated topical steroid, vasoconstriction assay, and clinical trial. South Med J 1972;66:325-8. 9. Henrijean A, Lapiere CM. Clinical evaluation of desonide cream. Curr Ther Res 1983;33:775-81.