Pharmacology and Treatment Dermatology 1992;184:51-53
C. P. L. L.
Bergstedt'' Gamborg Nielsen1' Kcuisson" Stwmberga
Treatment of Nummular Psoriasis with a Clobetasol Propionate Stick
Department of Dermatology. Varbcrg Hospital. Varbcrg; Department of Pharmacological Chemistry, Central Hospital. Bodcn. Sweden
Abstract Twenty-two consecutive patients with nummular psoriasis were treated with a 0.05% clobetasol propionate stick on the right side of the body and with 0.05% clobetasol propionate ointment (Dcrmovatc®, Glaxo) on the left according to an intermittent application schedule. The trial was open and lasted for 3 weeks. The patients were assessed at the beginning and at the end of the trial. The vari ables studied included: an overall clinical assessment, assessment of the lesion area, scaling, erythema and thickness and the amount of clobetasol propionate used during the trial, and a questionnaire on patients' opinions about hygienic and cosmetic qualities of the stick. No significant difference was found between the stick and corresponding ointment. From a hygienic and cosmetic point of view, the patients preferred the stick formulation.
Introduction
Material and Methods
The potent steroids used in the treatment of skin condi tions arc usually prepared in creams and ointments. Patients, however, often consider these unhygienic and cosmetically unappealing, and more acceptable methods of application ought to be better appreciated. Previously, it has been shown that patients with nummu lar psoriasis prefer a betamethasone valerate stick to the corresponding ointment. Betnovate® (Glaxo), and that no significant difference between the two formulations w'as found [1,2]. Based on these experiences it was considered of interest to study the compliance and efficacy of a 0.05% clobetasol propionate test stick with the commercially available 0.05% clobetasol propionate ointment Dcrmo vatc® (Glaxo Lakemedel AB. Molndal. Sweden). The test stick was prepared at the Department of Pharmacological Chemistry, Central Hospital, Bodcn. Sweden.
Received: April 16. 1991
Accepted: May 3. 1991
Twenty-three consecutive patients (9 women and 14 men, average age 37 years, range 18-72 years) suffering from symmetrical nummular psoriasis entered the study. The patients had not been treated with antipsoriatic compounds in the 3 months preceding the study, and they were forbidden to use any other type of treatment besides cmmollients during the study period. The trial was performed during February, March and April and during September, October and November 1990. The trial was designed its an open study, using the 0.05% clobeta sol propionate stick on the right-hand side of the body and the 0.05% clobetasol propionate ointment on the left. The patients were pro vided with a sufficient number of sticks and 25-gram ointment tubes. The sticks were produced at the Department of Pharmacological Chemistry, Central Hospital, Bodcn. Sweden, and based on simple traditional methods - clobetasol propionate 50 mg. lactosum Eur. 450 mg. cacao oleum nord. 25 g. paraffinum solidum PB 88 25 g. vaselinum album USP ad 100 g - and dispensed into 25-gram plastic cases. The sticks were allowed to solidify while constantly rotated on a spe cially designed rotator to avoid unequal dispersion of ingredients. The concentration of clobetasol propionate in the top and bottom of ran-
P. Gamborg Nielsen, Department of Dermatology. Varbcrg Hospital. S—132 85 Varbcrg. Sw eden"
© 1992 Karger AG. Basel 1018-8665/92/1841 -(X)51 S 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 6:51:24 PM
Key Words Psoriasis Clobetasol propionate Stick formulation
Table 1. Intermittent treatment schema for Dermovatc ointment, according to Prof. Halvor M0ller. Department of Dermatology. Uni versity of Lund, Malmö. Sweden (original in Swedish)
•
Application twice daily of Dermovatc ointment for 4 days
• O Treatment with non-steroid ointments (such as Merck's O ointment base or 2% salicylic acid in white petrolatum) twice O daily for 3 days •
•
Treatment with Dermovatc ointment twice daily for 2 days
O Treatment with non-steroid ointments twice daily for 2 days O •
Treatment with Dermovatc ointment twice daily for I day
O Treatment with non-steroid ointment twice daily for 1 day •
The initial treatment is completed with Dermovatc ointment twice daily for 1 day
Maintenance treatment: Dermovatc ointment should be applied on 2 evenings a week, for example on Mondays and Thursdays. On the remaining days of the week, non-steroid ointments should be used at need.
Results Twenty-two patients completed the study. One patient did not return at the final examination despite repeated requests. Lesion areas comprised 10% of the skin surface in 5 (22.7%) patients and in the remaining 5%. No statisti cally significant difference between stick and ointment con cerning lesion thickness, scaling or lesion colour was docu mented during the 3-week treatment period (table 2). A tendency to a better clinical result of the ointment could be noticed at the final clinical .examination. Reduction of lesion areas during the trial was statistically the same on both sides of the body. However, the patients used on aver age 20% more ointment than stick (table 3). At the clinical assessment and by the patient’s subjective opinion of treat ment effect no significant difference between the two courses of treatment was shown (table 2). It was a consis tent interpretation that the ointment was more effective than the corresponding stick formulation. Results of the questionnaire, which the patients com pleted at the end of the trial, arc shown in table 4. No patients reported any local allergic or irritant reac tions due to the clobetasol propionate stick.
Discussion
32
Significant differences between the clobetasol propio nate stick and the corresponding ointment were not found; however, at the final clinical examination the efficacy of the ointment appeared more impressive. During the trial the patients consumed about 20% more ointment than stick, and since no significant difference was found between the two courses of treatment, it depended most likely on the composition of the vehicle. Apart from galenical differ ences the stick vehicle is more occlusive and probably, therefore, more effective. Application of creams and oint ments is generally imprecise compared with the use of sticks and may also explain partly the overconsumption of ointment. Generally patients preferred the stick formula tion; however, the sticks for the trial were prepared in unappealing test plastic cases, and a better compliance should be achieved by using manufactured cases with dif ferent stick dimensions and more attractive designs. A steroid stick formulation may replace creams and ointments for other dermatological disorders, especially when a high level of accuracy is demanded.
Bergstedt/Gamborg Nielsen/ Karlsson/Strömbcrg
Treatment of Nummular Psoriasis with a Clobetasol Propionate Stick
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 6:51:24 PM
domly selected sticks was assayed after extraction from different parts of the sticks by reversed-phase liquid chromatography and UV detec tion at the absorption maximum of the steroid. The stick was compared with the commercially available 0.03% clobetasol propionate ointment Dermovatc (Glaxo). Clobctasol pro pionate stick and ointment were applied according to the application schema recommended by Prof. Halvor Möller. Department of Dermatology. Lund University. Malmö. Sweden (table I) |3. 4|. Treatment was limited to psoriatic lesions on the body, and the patients were not allowed to apply the stick or ointment to the face or intertriginous regions. The average and total amount of clobetasol propionate used during the 3-weck period was calculated. Each patient underwent a clinical evaluation, selected symmetrical lesions were outlined on a transparent sheet and transferred to X-ray film and this area was cut out and weighed on an electric balance (Type AC Adapter. DC 13V. Tokyo. Japan). A clinical assessment of lesion thickness, scaling and erythema according to a simple score ranging from 0 to 3 (0 = normal skin. l=slight, 2 = medium. 3 = severe) was performed before and at the end of the trial. At the final examination an overall clinical assessment was performed, and improvement of lesions and the patient's subjec tive opinion of treatment results was classified according to the same grading scale. In connection with the final examination, the patients were interviewed about how they had applied the steroid prepara tions. whether or not they had used protective gloves and how the tubes were stored. They were also interviewed about cosmetic and hygienic aspects of the preparations. Side effects were recorded. The % test was used for the statistical calculations of difference between means.
Table 2. Clinical scores (mean values ±SD ) of psoriatic lesions in 22 patients and the overall clinical assessment together with patients' opinion of treatment effect
Stick
Scaling Erythema Thickness Objective assessment Subjective opinion
Ointment
before
after
before
after
2.(K>± 0.71 1.95 ±0.65 2.32 ±0.73 2.27 ±0.69 2.41 ±0.54
0.36 ±0.19 0.68 ±0.21 0.77 ±0.16 0.91 ±0.24 0.86 ±0.22
2.00 ±0.58 1.95 ±0.65 2.32 ±0.73 2.27 ±0.69 2.41 ±0.54
0.23 ±0.17 0.68 ±0.14 0 .5 3 ± 0 .15 0.77 ±0.20 0.73 ±0.14
0 = Normal skin; 1= slight ; 2 = medium; 3 = severe.
Table 4. Questionnaire given to patients concerning application methods, cosmetic and hygienic aspects of steroid stick and ointment (percentages in parentheses)
References
Stick Ointment
Lesion areas, cm2
Amount of stick and ointment, g
Amount of clobetasol propionate, mg
38.1 ± 12.1 42.2+15.3
9.44± 1.19 11.63 ±2.73
0.21±0.059 0.26±0.042
Yes Did you use gloves when applying creams and ointments? Did you apply creams and ointments outside lesions? Did you find creams and ointments greasy and unpleasant to use? Did you keep creams and ointments in plastic bags? Did you find the stick cosmetically more attractive? Was the stick easier to look after and transport? Is it safer not to touch steroid creams or ointments with your hands during treatment? Did you find the stick more hygienic? Was the stick easier to use than the ointment? Was it easier to avoid application around the lesion with the stick? Should you prefer the stick to the ointment in the treatment of your psoriasis?
i •>
Bergstedt C. Gamborg Nielsen P. Karlsson L. Strömberg L: Stick formulation for topical ste roid therapy. Dermatol Treat, in press. Gamborg Nielsen P: Treatment of nummular psoriasis with steroid sticks; in: Current Topics on Dermatology. Proceedings of a Symposium held at Regent's College. London. December 1989. Winchester. Theracom. 1990.
3
4
No
Indifferent
1 (4.5)
21 (95.5)
0
9 (40.9)
13 (59.1)
0
21 (95.5)
1 (4.5)
0
11 (50.0)
10 (45.5)
19 (86.4)
3 (13.6)
0
18 (81.8)
1 (4.5)
3 (13.7)
14 (63.6) 16 (72.7) 15 (68.2)
4 (18.2) 4 (18.2) 3 (13.6)
4 (18.2) 2 (9.1) 4 (18.2)
16 (72.7)
1 (4.5)
5 (22.8)
21 (95.5)
1 (4.5)
0
1 (4.5)
Hradil E. Lindström C. Möller H; Intermittent treatment of psoriasis with clobetasol propio nate. Acta Derm Vcncrcol (Stockh) 1978: 58:375-377. Möller H. Svartholm H. Dahl G: Intermittent maintenance therapy in chronic hand eczema with clobetasol propionate and flupreniden acetate. Curr Med Res Opin 1983:9:640-644.
53
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 6:51:24 PM
Table 3. The m ean±SD amount of stick, ointment and clobetasol propionate together with the m can±SD difference of cleared lesion areas in the two courses of treatment (22 patients)
C. P. L. L.
Bergstedt'' Gamborg Nielsen1' Kcuisson" Stwmberga
Treatment of Nummular Psoriasis with a Clobetasol Propionate Stick
Department of Dermatology. Varbcrg Hospital. Varbcrg; Department of Pharmacological Chemistry, Central Hospital. Bodcn. Sweden
Abstract Twenty-two consecutive patients with nummular psoriasis were treated with a 0.05% clobetasol propionate stick on the right side of the body and with 0.05% clobetasol propionate ointment (Dcrmovatc®, Glaxo) on the left according to an intermittent application schedule. The trial was open and lasted for 3 weeks. The patients were assessed at the beginning and at the end of the trial. The vari ables studied included: an overall clinical assessment, assessment of the lesion area, scaling, erythema and thickness and the amount of clobetasol propionate used during the trial, and a questionnaire on patients' opinions about hygienic and cosmetic qualities of the stick. No significant difference was found between the stick and corresponding ointment. From a hygienic and cosmetic point of view, the patients preferred the stick formulation.
Introduction
Material and Methods
The potent steroids used in the treatment of skin condi tions arc usually prepared in creams and ointments. Patients, however, often consider these unhygienic and cosmetically unappealing, and more acceptable methods of application ought to be better appreciated. Previously, it has been shown that patients with nummu lar psoriasis prefer a betamethasone valerate stick to the corresponding ointment. Betnovate® (Glaxo), and that no significant difference between the two formulations w'as found [1,2]. Based on these experiences it was considered of interest to study the compliance and efficacy of a 0.05% clobetasol propionate test stick with the commercially available 0.05% clobetasol propionate ointment Dcrmo vatc® (Glaxo Lakemedel AB. Molndal. Sweden). The test stick was prepared at the Department of Pharmacological Chemistry, Central Hospital, Bodcn. Sweden.
Received: April 16. 1991
Accepted: May 3. 1991
Twenty-three consecutive patients (9 women and 14 men, average age 37 years, range 18-72 years) suffering from symmetrical nummular psoriasis entered the study. The patients had not been treated with antipsoriatic compounds in the 3 months preceding the study, and they were forbidden to use any other type of treatment besides cmmollients during the study period. The trial was performed during February, March and April and during September, October and November 1990. The trial was designed its an open study, using the 0.05% clobeta sol propionate stick on the right-hand side of the body and the 0.05% clobetasol propionate ointment on the left. The patients were pro vided with a sufficient number of sticks and 25-gram ointment tubes. The sticks were produced at the Department of Pharmacological Chemistry, Central Hospital, Bodcn. Sweden, and based on simple traditional methods - clobetasol propionate 50 mg. lactosum Eur. 450 mg. cacao oleum nord. 25 g. paraffinum solidum PB 88 25 g. vaselinum album USP ad 100 g - and dispensed into 25-gram plastic cases. The sticks were allowed to solidify while constantly rotated on a spe cially designed rotator to avoid unequal dispersion of ingredients. The concentration of clobetasol propionate in the top and bottom of ran-
P. Gamborg Nielsen, Department of Dermatology. Varbcrg Hospital. S—132 85 Varbcrg. Sw eden"
© 1992 Karger AG. Basel 1018-8665/92/1841 -(X)51 S 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 6:51:24 PM
Key Words Psoriasis Clobetasol propionate Stick formulation
Table 1. Intermittent treatment schema for Dermovatc ointment, according to Prof. Halvor M0ller. Department of Dermatology. Uni versity of Lund, Malmö. Sweden (original in Swedish)
•
Application twice daily of Dermovatc ointment for 4 days
• O Treatment with non-steroid ointments (such as Merck's O ointment base or 2% salicylic acid in white petrolatum) twice O daily for 3 days •
•
Treatment with Dermovatc ointment twice daily for 2 days
O Treatment with non-steroid ointments twice daily for 2 days O •
Treatment with Dermovatc ointment twice daily for I day
O Treatment with non-steroid ointment twice daily for 1 day •
The initial treatment is completed with Dermovatc ointment twice daily for 1 day
Maintenance treatment: Dermovatc ointment should be applied on 2 evenings a week, for example on Mondays and Thursdays. On the remaining days of the week, non-steroid ointments should be used at need.
Results Twenty-two patients completed the study. One patient did not return at the final examination despite repeated requests. Lesion areas comprised 10% of the skin surface in 5 (22.7%) patients and in the remaining 5%. No statisti cally significant difference between stick and ointment con cerning lesion thickness, scaling or lesion colour was docu mented during the 3-week treatment period (table 2). A tendency to a better clinical result of the ointment could be noticed at the final clinical .examination. Reduction of lesion areas during the trial was statistically the same on both sides of the body. However, the patients used on aver age 20% more ointment than stick (table 3). At the clinical assessment and by the patient’s subjective opinion of treat ment effect no significant difference between the two courses of treatment was shown (table 2). It was a consis tent interpretation that the ointment was more effective than the corresponding stick formulation. Results of the questionnaire, which the patients com pleted at the end of the trial, arc shown in table 4. No patients reported any local allergic or irritant reac tions due to the clobetasol propionate stick.
Discussion
32
Significant differences between the clobetasol propio nate stick and the corresponding ointment were not found; however, at the final clinical examination the efficacy of the ointment appeared more impressive. During the trial the patients consumed about 20% more ointment than stick, and since no significant difference was found between the two courses of treatment, it depended most likely on the composition of the vehicle. Apart from galenical differ ences the stick vehicle is more occlusive and probably, therefore, more effective. Application of creams and oint ments is generally imprecise compared with the use of sticks and may also explain partly the overconsumption of ointment. Generally patients preferred the stick formula tion; however, the sticks for the trial were prepared in unappealing test plastic cases, and a better compliance should be achieved by using manufactured cases with dif ferent stick dimensions and more attractive designs. A steroid stick formulation may replace creams and ointments for other dermatological disorders, especially when a high level of accuracy is demanded.
Bergstedt/Gamborg Nielsen/ Karlsson/Strömbcrg
Treatment of Nummular Psoriasis with a Clobetasol Propionate Stick
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 6:51:24 PM
domly selected sticks was assayed after extraction from different parts of the sticks by reversed-phase liquid chromatography and UV detec tion at the absorption maximum of the steroid. The stick was compared with the commercially available 0.03% clobetasol propionate ointment Dermovatc (Glaxo). Clobctasol pro pionate stick and ointment were applied according to the application schema recommended by Prof. Halvor Möller. Department of Dermatology. Lund University. Malmö. Sweden (table I) |3. 4|. Treatment was limited to psoriatic lesions on the body, and the patients were not allowed to apply the stick or ointment to the face or intertriginous regions. The average and total amount of clobetasol propionate used during the 3-weck period was calculated. Each patient underwent a clinical evaluation, selected symmetrical lesions were outlined on a transparent sheet and transferred to X-ray film and this area was cut out and weighed on an electric balance (Type AC Adapter. DC 13V. Tokyo. Japan). A clinical assessment of lesion thickness, scaling and erythema according to a simple score ranging from 0 to 3 (0 = normal skin. l=slight, 2 = medium. 3 = severe) was performed before and at the end of the trial. At the final examination an overall clinical assessment was performed, and improvement of lesions and the patient's subjec tive opinion of treatment results was classified according to the same grading scale. In connection with the final examination, the patients were interviewed about how they had applied the steroid prepara tions. whether or not they had used protective gloves and how the tubes were stored. They were also interviewed about cosmetic and hygienic aspects of the preparations. Side effects were recorded. The % test was used for the statistical calculations of difference between means.
Table 2. Clinical scores (mean values ±SD ) of psoriatic lesions in 22 patients and the overall clinical assessment together with patients' opinion of treatment effect
Stick
Scaling Erythema Thickness Objective assessment Subjective opinion
Ointment
before
after
before
after
2.(K>± 0.71 1.95 ±0.65 2.32 ±0.73 2.27 ±0.69 2.41 ±0.54
0.36 ±0.19 0.68 ±0.21 0.77 ±0.16 0.91 ±0.24 0.86 ±0.22
2.00 ±0.58 1.95 ±0.65 2.32 ±0.73 2.27 ±0.69 2.41 ±0.54
0.23 ±0.17 0.68 ±0.14 0 .5 3 ± 0 .15 0.77 ±0.20 0.73 ±0.14
0 = Normal skin; 1= slight ; 2 = medium; 3 = severe.
Table 4. Questionnaire given to patients concerning application methods, cosmetic and hygienic aspects of steroid stick and ointment (percentages in parentheses)
References
Stick Ointment
Lesion areas, cm2
Amount of stick and ointment, g
Amount of clobetasol propionate, mg
38.1 ± 12.1 42.2+15.3
9.44± 1.19 11.63 ±2.73
0.21±0.059 0.26±0.042
Yes Did you use gloves when applying creams and ointments? Did you apply creams and ointments outside lesions? Did you find creams and ointments greasy and unpleasant to use? Did you keep creams and ointments in plastic bags? Did you find the stick cosmetically more attractive? Was the stick easier to look after and transport? Is it safer not to touch steroid creams or ointments with your hands during treatment? Did you find the stick more hygienic? Was the stick easier to use than the ointment? Was it easier to avoid application around the lesion with the stick? Should you prefer the stick to the ointment in the treatment of your psoriasis?
i •>
Bergstedt C. Gamborg Nielsen P. Karlsson L. Strömberg L: Stick formulation for topical ste roid therapy. Dermatol Treat, in press. Gamborg Nielsen P: Treatment of nummular psoriasis with steroid sticks; in: Current Topics on Dermatology. Proceedings of a Symposium held at Regent's College. London. December 1989. Winchester. Theracom. 1990.
3
4
No
Indifferent
1 (4.5)
21 (95.5)
0
9 (40.9)
13 (59.1)
0
21 (95.5)
1 (4.5)
0
11 (50.0)
10 (45.5)
19 (86.4)
3 (13.6)
0
18 (81.8)
1 (4.5)
3 (13.7)
14 (63.6) 16 (72.7) 15 (68.2)
4 (18.2) 4 (18.2) 3 (13.6)
4 (18.2) 2 (9.1) 4 (18.2)
16 (72.7)
1 (4.5)
5 (22.8)
21 (95.5)
1 (4.5)
0
1 (4.5)
Hradil E. Lindström C. Möller H; Intermittent treatment of psoriasis with clobetasol propio nate. Acta Derm Vcncrcol (Stockh) 1978: 58:375-377. Möller H. Svartholm H. Dahl G: Intermittent maintenance therapy in chronic hand eczema with clobetasol propionate and flupreniden acetate. Curr Med Res Opin 1983:9:640-644.
53
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 6:51:24 PM
Table 3. The m ean±SD amount of stick, ointment and clobetasol propionate together with the m can±SD difference of cleared lesion areas in the two courses of treatment (22 patients)
