J In! Med Res (1982) 10,414

Alclometasone Dipropionate in Psoriasis: A Clinical Study Anand Aggerwal, MB, BS, PhD, Associate Area Director, International Medical Research, Schering Canada Inc., Pointe Claire, Quebec, Canada Stuart Maddin, MD, FRCP, Clinical Professor of Dermatology, Department of Medicine. University ofBritish Columbia, Vancouver, B.C.. Canada

In a parallel group design, and using a 'blind evaluator' technique, alclometasone cream 0·05% and clobetasone butyrate cream 0·5% applied twice a day for 21 days were compared in thirty-one patients presenting with psoriasis. Erythema, induration and scaling were assessed at the start of treatment. Seven, 14 and 21 days later, effects of the two treatments were assessed and recorded together with the physician's global evaluation of overall improvement. Both drugs had similar beneficial effects on the clinical signs. No adverse experience was reported and the overall results indicate that alclometasone and clobetasone have comparable efficacy and safety.

Introduction Psoriasis, a chronic dermatitis and a life-long disorder, affects all ages (Schneidman 1982) and is estimated to be present in approximately 2·5% of the population. The disease is characterized by thickened and reddened plaques of skin, formed by rapid turn-over of cells in the epidermis (Champion 1981). The plaques shed scales and itch; they occur most commonly on the scalp, elbows, knees and legs and respond favourably to topical applications of corticosteroids. (7a-chloro-ll~,17a,21Alclometasone trihydroxy-16 a methyl-l,4- pregnadiene-3,20 dione 17,21-dipropionate) is a new synthetic non-fluorinated corticoid of mild to moderate potency. It has topical anti-inflammatory activity and a low potential for producing local

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and systemic corticosteroid side-effects. The objectives of this study were to compare the efficacy and safety of alclometasone cream (0·05%) and c1obetasone butyrate cream (0·5%), applied topically twice a day for 21 days, in the treatment of psoriasis. Study Design, Materials and Methods A. Study Design This was a comparative study using a randomized, parallel group design and a blind evaluator technique. Adults over the age of 18 years who met the following criteria were eligible for enrollment: • Skin condition pre-established for at least I month and diagnosed as stable. • Presence of three clinical signs, erythema, induration, and scaling with a severity score totaling 6 or more, graded on the following scale, 0 = absent, 1 = mild, 2 = moderate, 3 = severe.

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A Aggerwal and S Maddin Patients were randomly assigned to one of the two treatment groups. They were instructed to apply a thin layer of cream twice daily for 3 weeks, without occlusion, to areas of inflammation. Medication was given out by the unblinded research assistant; evaluations of drug efficacy and safety were made by one of us (S.M.) who did not know which drug the patients received (blind evaluator). Study areas could be located on the face, neck, trunk, and upper and lower extremities, but not on the hands, feet, or scalp. At a pre-trial visit, study procedures were discussed and each patient gave written, informed consent to participate in the study. Patients were to observe the following restrictions during the study: • No medication other than the study preparation was to be applied to the study area or administered systemically. • Tar baths, ultraviolet light or Grenz ray therapy were not to be used. • Keratolytic or tar shampoos could be used if necessary, but treatment areas were to be avoided. • If a hypnotic agent had been customary, its use could be continued. • Sun exposure and changes in exercise habits or environment were to be avoided. Patients were given medication at the initial visit, and at the end of 1 and 2 weeks of treatment. Weekly follow-up visits could be made 1 day earlier or 1 day later, but missing more than three applications or applying three additional treatments invalidated the case report. Additionally, patients were not to apply treatment for at least 3 hours prior to the follow-up visits.

B. Study Population Thirty-one patients (sixteen alclometasone, fifteen clobetasone) were empanelled; all were evaluated for safety and efficacy. The two treatment groups were not statistically different with respect to age, race, or per cent of the body involved with the skin condition (P> 0·10). Patients were between the ages of 20 and 73 years. Sixty-eight per cent of the patients had up to 25% of the body involved with the skin condition.

C. Evaluation ofEfficacy

Each of the three clinical signs (erythema, induration and scaling) was graded separately at the pre-treatment visit and after Weeks 1,2 and 3 of therapy using the same scoring system presented in Section A, Study Design. Physician's global evaluation of overall improvement in the condition of the treated areas was made at each of the three weekly follow-up visits as follows: 1 = Cleared: 100% improvement except for residual discoloration. 2 = Marked improvement: 75% improvement but less than 100% clearance of signs and symptoms monitored. 3 = Moderate improvement: 50% improvement to less than 75% clearance of signs and symptoms monitored. 4 = Slight improvement: less than 50% improvement of signs and symptoms monitored. 5 = No change: no detectable improvement from baseline evaluation. 6 = Exacerbation: flare at sites being studied.

D. Evaluation ofSafety Patients were queried and evaluated clinically at each follow-up visit for evidence of adverse experiences. The relationship of the adverse experience to treatment was characterized as none, possible, probable, or definite. In the final tabulation, experiences characterized as possible, probable, or definite were attributed to treatment; those included in the 'none' category were not attributed to treatment.

E. Statistical Methods Demographic data were tested for treatment group comparability at entry into the study using the Wilcoxon two sample test and Fisher's exact test. Pre-treatment disease severity in the two groups was analyzed by the t test. Between group comparisons of efficacy parameters, individual and total disease sign scores (sum of scores for erythema, induration, and scaling) and the physician's global evaluation at each follow-up visit were made using the t test. Results for each week

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The Journal ofInternational Medical Research

were analyzed separately. Data from the last valid visit for each patient end-point of treatment were also used in the statistical analysis whenever patients dropped out of the study. If the last visit was invalid only because of visit spacing, it was included in the endpoint analysis.

end-point of treatment. Changes in mean scores from pre-treatment to end-point in the clobetasone group were of comparable magnitude. Mean improvement in total disease sign score at the end-point of treatment was 45% for alclometasone-treated patients and 50% for clobetasone-treated patients. There were no statistically significant differences between the treatment groups (P > o· 10). As shown in Table 2 when improvement following treatment was categorized by percentiles, similar numbers of alclometasoneand clobetasone-treated patients were in each percentile at each of the three weekly evaluations, and at end-point of treatment. There were no statistically significant differences between the groups (P > 0·10). The physician's global evaluation of treatment also showed similar improvement in both alclometasone and clobetasone patients in the signs and symptoms of the skin condition at end-point of treatment (Table 3).

Results

Alclometasone and clobetasone had similar beneficial effects on each of the clinical signs, erythema, induration and scaling and on the total clinical sign score (Table 1). In the alclometasone group, erythema and scaling had mean pre-treatment sign scores in the moderate to severe range (2·56, respectively) improving to 1·56 erythema and 1·50 scaling in the slight to moderate severity range at endpoint of treatment. Mean induration score pretreatment was 1·63 in the slight to moderate range improving to 0·69, of slight severity, at

Table 1 Mean clinical sign scores"

Number of patients

Erythema

Induration

Scaling

Total« sign score

2·56 2·67

1·63 1·33

2·56 2·60

6·75 6·60

-

2·25 2·07

1·06 1·00

2·00 1·80

5·31 4·87

22 26

1·67 1·73

0·73 0·73

1·47 1·47

3·87 3·93

43 40

1·53 1·40

0·67 0·53

1·47 1·33

3·67 3·27

50

IS 16 15

1·56 1·40

0·69 0·53

1·50 1·33

3·75 3·27

45 50

Visit

Treatment

Pre-treatment

Alc1ometasone Clobetasonc butyrate

16

Alclometasone Clobetasone butyrate

16

Alclometasone Clobetasone butyrate

15#

Alclometasone Clobetasone butyrate

15#

Alc1ometasone Clobetasone butyrate

Week I

Week 2

Week 3

I End-point

IS

IS

IS

Clinical signs t

Percent» improvement -

SO

-No significance between group differences for any parameter (P > 0·05) tErythema, induration and scaling scores: I = slight; 2 = moderate; and 3 = severe Difference between the total scores at treatment and pre-treatment divided by the total score at pre-treatment multiplied by 100 # Patient dropped out of the study for extraneous reasons not related to treatment

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Table 2 Number of patients showing improvement"

Visit

Number of patients

Improvement