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Current Medical Research and Opinion
Vol. 3, No. 4,1975
Double-blind comparison between two new toDical corticosteroids. hakinonid; 0.1 % and clobetasol propionate cream 0.05 X,
Johsn Bleeker, M.D. Dermatology Department, General Hospital, Lidkoping und Skovde, Sweden
Curr. med. Res. Opin., (1975), 3,225.
Received: 5th May, 1975
Summary A new steroid, halcinonide, was compared with clobetasol propionate cream in 100 patients with a variety of skin disorders. The study was conducted as a double-blind, paired comparison with the preparations being given twice daily. Results obtained over a 14-da.y period of therapy showed remarkably similar eficacy for both preparations.
Kelp wordr: Halcinonide - rlohetasol- closage forms - skin diseases
Introduction Since hydrocortisone was first introduced for topical use in 1952, the synthesis of other topically-active corticosteroids continues to add to the dermatologists’ armamentarium. In recent years, the improved anti-inflammatory effect of these drugs has been further enhanced by an awareness of the importance the vehicle plays in the formulation.3 For example, it has been shown that the solubility of the corticosteroid in the vehicle influences the amount released, the greatest release being obtained from preparations in which the active ingredient is optimally soluble. Recently, a new corticosteroid, halcinonide, has been made available in a specifically designed base, with a high content of propylene glycol, but containing sufficient water to maintain proper hydration of the stratum corneum.2 Leibsohn and Bagatell compared halcinonide with betamethasone 17-valeratein a double-blind paired comparison study and showed halcinonide to be statistically superior to betamethasone 17-valerate (p < 0.00 I). Clobetasol propionate,4 like halcinonide, is another double halogenated corticosteroid and obviously a comparison of these two preparations was the next logical step in research.
Material and methods One hundred patients with psoriasis or eczema were enrolled in a double-blind, paired comparison study. Only patients with bilateral lesions similar in severity, persistency and aetiology were included in the study. They were also selected for their ability to follow instructions carefully regarding application of the medication. The diagnoses were as follows: 53 patients had psoriasis (23 severe, 29 moderate, 225
Curr Med Res Opin Downloaded from informahealthcare.com by Cornell University on 12/27/14 For personal use only.
Double-blind comparison between two new topical corticosteroids,halcinonide 0.1% and clobetasol propionate cream 0.05%)
1 mild), 27 had atopic dermatitis (11 severe, 16 moderate) and 20 other types of eczema (1 2 severe, 8 moderate). The test preparations (halcinonide 0.1 % and clobetasol propionate cream 0.05 %) were packed identically in 30 g. tubes and designated for each patient’s left or right side in accordance with a table of random assignment. Tubes were labelled with the patient’s number and the side of the body to which its contents were to be applied. Patients were instructed to apply both preparations in similar fashion twice daily. All patients were examined after Week 1 and Week 2, so any difference in the rapidity of response of the lesions could be determined. Objective criteria for judging therapeutic response included a decrease in erythema, oedema, transudation, lichenification and scaling. Subjective criteria included relief of pruritus and pain. The following factors were taken into account in rating the overall therapeutic response for the entire treatment period: rapidity of onset of any therapeutic response; the maximum degree of clearing of lesions; and the maintenance of any response for the remainder of the treatment period. Apart from weekly assessments and preferences, an overall assessment for the 2-week period was made at the end of the trial.
Results The code was broken only after the I00 case reports were completed. The results are summarised in Tables I to IV.
Psoriasis Fifty-three patients had psoriasis and the preference for each preparation is given in Table I. Table I. Objective comparativeclinical response to treatment En patients with psoriasis
Time
No. Halcinonide patients superior evaluated Markedly Slightly
Clobetasol propionate superior
Drugs equally effective
Neither effective
3
Markedly Slightly
Week 1
53
3
13
1
11
22
Week 2
53
4
10
3
14
22
Overall
53
4
11
3
10
25
There was no statistical difference between the two preparations and a further analysis of the ‘equal’ responses showed that of the 25 patients an ‘excellent’ response was obtained with both preparations in 15, a ‘good’ response in 8, and a ‘fair’ response in 2. 226
Johan Bleeker
Atopic dermatitis Twenty-seven patients had atopic eczema and the results are shown in Table 11. Table II. Objective comparative dinical response to treatment in patients with atopic dermatitis
No. Halcinonide patients superior evaluated Markedly Slightly
Clobetasol propionate superior
Week 1
21
4
3
2
Week 2
27
4
2
Overall
21
4
3
Curr Med Res Opin Downloaded from informahealthcare.com by Cornell University on 12/27/14 For personal use only.
Time
Drugs equally effective
Neither effective
3
14
1
2
4
15
2
4
14
Markedly Slightly
Again, the 14 patients with an equal response were further analysed and 13 of these had an ‘excellent’ response and 1 had a ‘good’ response. Other types of eczema Twenty patients were included under a miscellaneous group of corticosteroid responsive dermatoses and the analysis of the group is shown in Table 111. Table IU. Objective comparative clinical response in patients with a variety of other dennatoses
No. Halcinonide patients superior evaluated Markedly Slightly
Time
20
Week 1
20
Overall
20
~
Drugs equally effective
Neither effective
Markedly Slightly
1 ~
Week 2
Clobetasol propionate superior
14
4
1 ~
~
~~
~
I
2
3
14
1
I
4
14
~
Again, the 14 patients with an equal response showed that 11 were ‘excellent’and 1 ‘good’ on both preparations. Overall response to treatment Table IV summarises the overall response to treatment in the 100 patients studied. Table IV. Overall clinical response in 100 patients studied Diagnosis
Excellent
Fair
Psoriasis
27
25
19
21
6
7
I
Atopic dermatitis
20
19
5
6
1
2
I
Others
12
14
8
5
Total
59
58
32
32
Good
Poor
1
7
10
2
221
Curr Med Res Opin Downloaded from informahealthcare.com by Cornell University on 12/27/14 For personal use only.
Double-blind comparison between two new topical corticosteroids, halcinonide 0.01?(, and cloberatol propionate cream 0.05”,,
The results show a remarkably consistent effect from the two double halogenated corticosteroids. Of the 2 patients who thought that halcinonide was ‘poor’, one complained of stinging and the other was a ‘difficult to please’ patient who thought clobetasol ‘fair’. Only 3 patients complained of side-effects out of 100 in the trial. One on clobetasol complained of stinging and of the 2 on halcinonide, one complained of stinging and the other of burning with erythema.
Discussion While each week’s response was assessed separately, the overall results were assessed at the second visit and some of these differed from the first and second assessment at Week 1 and Week 2 due to the initial differences diminishing or increasing from the first to the second week. The two preparations were remarkably similar in their efficacy and in their rapid onset of action. The clinical response was of a very high order and this is probably due to the fact that both are Group 111 double halogenated corticosteroids. Halcinonide has been formulated in a special bi-phasic base which has part of the steroid in solution with the other part in suspension. Bagatell’ has shown in in v i f m studies that this bi-phasic formulation gives a prolonged period of activity. It might be advantageous to test this hypothesis by carrying out a trial using halcinonide in this formulation once daily. It would certainly be in keeping with dermatological thinking to find ways of reducing total amounts of corticosteroid applied in chronic dermatoses amenable to this form of therapy, and a once-a-day regime for a limited period of time would be welcome to patients.
References
I . Bagatell, F. K . , (1974). Halcinonide: a qew potent topical anti-inflammatory drug. Cutictic, 14,459. 2. Leibsohn, E., and Bagatell, F. K . , (1974). Halcinonide in the treatment of corticosteroid responsive derniatoses. Brit. J . Derm., 90,435. 3. Maibach, H. I., and Stoughton, R. B., (1973). Topical corticosteroids. Med. Clinics N . Amer., 57, 1253. 4. Sparkes, C. G., and Wilson, L., (1974). The clinical evaluation of a new topical corticosteroid, clobetasol propionate. Brit. J . Deim., 90, 197.
228
Current Medical Research and Opinion
Vol. 3, No. 4,1975
Double-blind comparison between two new toDical corticosteroids. hakinonid; 0.1 % and clobetasol propionate cream 0.05 X,
Johsn Bleeker, M.D. Dermatology Department, General Hospital, Lidkoping und Skovde, Sweden
Curr. med. Res. Opin., (1975), 3,225.
Received: 5th May, 1975
Summary A new steroid, halcinonide, was compared with clobetasol propionate cream in 100 patients with a variety of skin disorders. The study was conducted as a double-blind, paired comparison with the preparations being given twice daily. Results obtained over a 14-da.y period of therapy showed remarkably similar eficacy for both preparations.
Kelp wordr: Halcinonide - rlohetasol- closage forms - skin diseases
Introduction Since hydrocortisone was first introduced for topical use in 1952, the synthesis of other topically-active corticosteroids continues to add to the dermatologists’ armamentarium. In recent years, the improved anti-inflammatory effect of these drugs has been further enhanced by an awareness of the importance the vehicle plays in the formulation.3 For example, it has been shown that the solubility of the corticosteroid in the vehicle influences the amount released, the greatest release being obtained from preparations in which the active ingredient is optimally soluble. Recently, a new corticosteroid, halcinonide, has been made available in a specifically designed base, with a high content of propylene glycol, but containing sufficient water to maintain proper hydration of the stratum corneum.2 Leibsohn and Bagatell compared halcinonide with betamethasone 17-valeratein a double-blind paired comparison study and showed halcinonide to be statistically superior to betamethasone 17-valerate (p < 0.00 I). Clobetasol propionate,4 like halcinonide, is another double halogenated corticosteroid and obviously a comparison of these two preparations was the next logical step in research.
Material and methods One hundred patients with psoriasis or eczema were enrolled in a double-blind, paired comparison study. Only patients with bilateral lesions similar in severity, persistency and aetiology were included in the study. They were also selected for their ability to follow instructions carefully regarding application of the medication. The diagnoses were as follows: 53 patients had psoriasis (23 severe, 29 moderate, 225
Curr Med Res Opin Downloaded from informahealthcare.com by Cornell University on 12/27/14 For personal use only.
Double-blind comparison between two new topical corticosteroids,halcinonide 0.1% and clobetasol propionate cream 0.05%)
1 mild), 27 had atopic dermatitis (11 severe, 16 moderate) and 20 other types of eczema (1 2 severe, 8 moderate). The test preparations (halcinonide 0.1 % and clobetasol propionate cream 0.05 %) were packed identically in 30 g. tubes and designated for each patient’s left or right side in accordance with a table of random assignment. Tubes were labelled with the patient’s number and the side of the body to which its contents were to be applied. Patients were instructed to apply both preparations in similar fashion twice daily. All patients were examined after Week 1 and Week 2, so any difference in the rapidity of response of the lesions could be determined. Objective criteria for judging therapeutic response included a decrease in erythema, oedema, transudation, lichenification and scaling. Subjective criteria included relief of pruritus and pain. The following factors were taken into account in rating the overall therapeutic response for the entire treatment period: rapidity of onset of any therapeutic response; the maximum degree of clearing of lesions; and the maintenance of any response for the remainder of the treatment period. Apart from weekly assessments and preferences, an overall assessment for the 2-week period was made at the end of the trial.
Results The code was broken only after the I00 case reports were completed. The results are summarised in Tables I to IV.
Psoriasis Fifty-three patients had psoriasis and the preference for each preparation is given in Table I. Table I. Objective comparativeclinical response to treatment En patients with psoriasis
Time
No. Halcinonide patients superior evaluated Markedly Slightly
Clobetasol propionate superior
Drugs equally effective
Neither effective
3
Markedly Slightly
Week 1
53
3
13
1
11
22
Week 2
53
4
10
3
14
22
Overall
53
4
11
3
10
25
There was no statistical difference between the two preparations and a further analysis of the ‘equal’ responses showed that of the 25 patients an ‘excellent’ response was obtained with both preparations in 15, a ‘good’ response in 8, and a ‘fair’ response in 2. 226
Johan Bleeker
Atopic dermatitis Twenty-seven patients had atopic eczema and the results are shown in Table 11. Table II. Objective comparative dinical response to treatment in patients with atopic dermatitis
No. Halcinonide patients superior evaluated Markedly Slightly
Clobetasol propionate superior
Week 1
21
4
3
2
Week 2
27
4
2
Overall
21
4
3
Curr Med Res Opin Downloaded from informahealthcare.com by Cornell University on 12/27/14 For personal use only.
Time
Drugs equally effective
Neither effective
3
14
1
2
4
15
2
4
14
Markedly Slightly
Again, the 14 patients with an equal response were further analysed and 13 of these had an ‘excellent’ response and 1 had a ‘good’ response. Other types of eczema Twenty patients were included under a miscellaneous group of corticosteroid responsive dermatoses and the analysis of the group is shown in Table 111. Table IU. Objective comparative clinical response in patients with a variety of other dennatoses
No. Halcinonide patients superior evaluated Markedly Slightly
Time
20
Week 1
20
Overall
20
~
Drugs equally effective
Neither effective
Markedly Slightly
1 ~
Week 2
Clobetasol propionate superior
14
4
1 ~
~
~~
~
I
2
3
14
1
I
4
14
~
Again, the 14 patients with an equal response showed that 11 were ‘excellent’and 1 ‘good’ on both preparations. Overall response to treatment Table IV summarises the overall response to treatment in the 100 patients studied. Table IV. Overall clinical response in 100 patients studied Diagnosis
Excellent
Fair
Psoriasis
27
25
19
21
6
7
I
Atopic dermatitis
20
19
5
6
1
2
I
Others
12
14
8
5
Total
59
58
32
32
Good
Poor
1
7
10
2
221
Curr Med Res Opin Downloaded from informahealthcare.com by Cornell University on 12/27/14 For personal use only.
Double-blind comparison between two new topical corticosteroids, halcinonide 0.01?(, and cloberatol propionate cream 0.05”,,
The results show a remarkably consistent effect from the two double halogenated corticosteroids. Of the 2 patients who thought that halcinonide was ‘poor’, one complained of stinging and the other was a ‘difficult to please’ patient who thought clobetasol ‘fair’. Only 3 patients complained of side-effects out of 100 in the trial. One on clobetasol complained of stinging and of the 2 on halcinonide, one complained of stinging and the other of burning with erythema.
Discussion While each week’s response was assessed separately, the overall results were assessed at the second visit and some of these differed from the first and second assessment at Week 1 and Week 2 due to the initial differences diminishing or increasing from the first to the second week. The two preparations were remarkably similar in their efficacy and in their rapid onset of action. The clinical response was of a very high order and this is probably due to the fact that both are Group 111 double halogenated corticosteroids. Halcinonide has been formulated in a special bi-phasic base which has part of the steroid in solution with the other part in suspension. Bagatell’ has shown in in v i f m studies that this bi-phasic formulation gives a prolonged period of activity. It might be advantageous to test this hypothesis by carrying out a trial using halcinonide in this formulation once daily. It would certainly be in keeping with dermatological thinking to find ways of reducing total amounts of corticosteroid applied in chronic dermatoses amenable to this form of therapy, and a once-a-day regime for a limited period of time would be welcome to patients.
References
I . Bagatell, F. K . , (1974). Halcinonide: a qew potent topical anti-inflammatory drug. Cutictic, 14,459. 2. Leibsohn, E., and Bagatell, F. K . , (1974). Halcinonide in the treatment of corticosteroid responsive derniatoses. Brit. J . Derm., 90,435. 3. Maibach, H. I., and Stoughton, R. B., (1973). Topical corticosteroids. Med. Clinics N . Amer., 57, 1253. 4. Sparkes, C. G., and Wilson, L., (1974). The clinical evaluation of a new topical corticosteroid, clobetasol propionate. Brit. J . Deim., 90, 197.
228
