J Int Med Res (1974) 2, 71

A Comparison of Metosyn and Betnovate in the Treatment of Eczema and Psoriasis W J Cunliffe, M D , BSc, MRCP, Leeds General Infirmary, Leeds, J Τ NichoUs, MA, MB, BS, Imperial Chemical Industries Limited, Mereside, Alderley Park, Macclesfield, England

England Pharmaceuticals

Division,

A double-blind, paired-lesion comparison of fluocinonide 0-05% in a fatty alcohol propylene glycol base and betameihasone-\l-valerate 0-1% cream in the treatment of patients with eczema or psoriasis, is described. The fluocinonide preparation, 'Metosyn\ was significantly superior to betamethasone-n-valerate in the treatment of patients with eczema. Both topical steroids were equally effective in the treatment of psoriasis. The advantage of fluocinonide over betamethasone-^-valerate was seen mainly in those patients who had been treated with betamethasone-\l-valerate preparations before the start of the investigation. Tolerance was equally good with both preparations.

Introduction The clinical effectiveness of a topical steroid preparation is dependent on the inherent potency of the steroid itself and the nature of the vehicle in which it is presented (Sarkany et al 1965, Busse et al 1969, Burdick, Poulsen & Place 1970, and Christie & MooreRobinson 1970). In order to use each of these factors to advantage, a new, highly active steroid, fluocinonide, has been formulated in a new type of base consisting of a fatty alcohol and propylene glycol (FAPG), the proportions of which have been chosen to enhance the release of the steroid (Poulsen et al 1968). Fluocinonide has been compared with standard topical steroids in the McKenzie blanching test (McKenzie & Stoughton 1962) and in this was found to be more effective than betamethasone-17-valerate (Stoughton

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• CH' -ch:

Fig 1 Fluocinonide (6ot, 93.-difluoro 11 β, 16α, 17α, 21 letrahydro.xy-pregna-í,4-diene-i, 20-dione 2\-acetate \e,\l-acetonide)

72

The Journal of International

1969, Coldman, Lockerbie & Laws 1971, and Sarkany, Hadgraft & Baker, unpublished data). Early open clinical assessments of fluocinonide 0 - 0 5 % in F A P G base ('Metosyn')* suggested that it is both an effective and an acceptable treatment for steroidresponsive inflammatory dermatoses (Nicholls 1972). Further studies of 'Metosyn' in which it was compared under double-blind con­ ditions with betamethasone-17-valerate (Portnoy & Sarkany 1972, Rosenberg 1971, and Binder & McCleary 1971), fluocortolone (Kalkoff 1972) and flumethasone pivalate (Baran 1972) creams in the treatment of eczema and psoriasis showed the new pre­ paration to have advantages over each of the established ones.

random code. Assessments of erythema, scaling, weeping, itching and percentage improvement were made at up to weekly intervals for a maximum of six weeks of the treatment. Any side-effects were also noted.

The present investigation was undertaken to compare 'Metosyn' with betamethasone17-valerate 0 - 1 % as 'Betnovate C r e a m ' t in the treatment of patients with eczema or psoriasis, and to determine the influence of previous treatment with betamethasone.

The simplest measure of comparative efficacy was based on the final global percen­ tage improvement score and the examining physician's opinion as to which side had improved more. The preferences are shown in Table 2 and Table 3 for eczema and psoriasis respectively. Probability values were cal­ culated using the sign test (Smart 1963), and values are given in brackets where levels of significance were detected.

Patients and Method A total of forty-seven patients entered the trial. Their distribution by sex, age and diagnosis is shown in Table 1. As can be seen from this table there was reasonable homogeneity of the groups. Further, the duration of the eczema or psoriasis prior to the study was very similar for the two sexes. This study comprised a double-blind, paired-lesion comparison of 'Metosyn' and 'Betnovate Cream' for the treatment of out­ patients with eczema or psoriasis. On entry to the trial, the duration of symptoms and a careful history of previous topical therapy was recorded for each patient. Pre-treatment assessments of the symmetrical bilateral lesions were made in which the characteristics erythema, scaling, weeping and itching were scored on the four point scale—absent, slight, moderate and severe. Patients were then given two tubes marked left and right, one con­ taining the fluocinonide formulation and the other the betamethasone cream. Applications of the two topical preparations were made three times a day without occlusion, the side of application being determined from a * Trademark—property of ICI Limited t Trademark—property of G l a x o Limited

Medical

Research

Efßcacy A patient was regarded as having responded if he showed some improvement in any of the parameters at the time of the final assessment. Of the twenty patients with eczema only one failed to show any response to 'Metosyn' and two failed to respond to 'Betnovate Cream'. Of the twenty-seven patients with psoriasis, twenty responded to both prepara­ tions, five to neither, one to 'Metosyn' only and one to 'Betnovate Cream' only.

As far as the individual symptoms of erythema, scaling, weeping and itching in eczema were concerned, fluocinonide proved to be significantly better (p < 0-01) than betamethasone in reducing erythema. Al­ though, numerically, fluocinonide improved the other symptoms more than beta­ methasone-17-valerate, these differences did not reach levels of statistical significance. In psoriasis both topical preparations were equally effective in alleviating the four symptoms. It was found that the preferences for 'Meto­ syn' over 'Betnovate Cream' mainly occurred in those patients who had received beta­ methasone-17-valerate preparations in the past (Tables 4 and 5). In only one psoriatic patient, who had previously been treated with betamethasone, was betamethasone-17valerate cream superior to the fluocinonide formulation. The results for those patients who had not received betamethasone-17-valerate cream preparations in the past are shown in Tables 6 and 7 for comparison.

f f J Cunliffe and J Τ Nicholls

73

Table 1 Shows distribution by sex, age and diagnosis

Condition

Sex

Eczema

Male

Eczema

Number patients

of Average

age

Age

range

8

30 years

4 - 7 0 years

Female

12

29 years

4 - 7 6 years

Psoriasis

Male

14

32 years

7 - 6 4 years

Psoriasis

Female

13

38 years

11-69 years

Table 2 Shows the results in patients with eczema

Number of patients better on Fluocinonide

Sex

Number of patients better on Betamethasone

Number of patients equally affected

Total

Male

2

1

5

8

Female

8

0(p < 001)

4

12

10

1 (p < 0 02)

9

20

Sex

Number of patients better on Fluocinonide

Number of patients better on Betamethasone

Number of patients equally affected

Total

Male

3

2

9

14

Female

2

2

9

13

Total

5

4

18

27

Total

Table 3 Shows the results in patients with psoriasis

Table 4 Shows the results in eczema patients who had received Betamethasone in the past

Sex

Number of patients better on Fluocinonide

Number of patients better on Betamethasone

Number of patients equally affected

Total

Male

2

0

0

2

Female

5

0(p < 01)

1

6

Total

7

0 ( p < 0 02)

1

8

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The Journal of International

Medical

Research

Table 5 Shows the results in psoriasis patients who had received Betamethasone in the past

Sex

Number of patients better on Fluocinonide

Number of patients better on Betamethasone

Number of patients equally affected

Male

3

0

1

4

Female

1

1

4

6

Total

4

1

5

10

Total

Table 6 Shows the results in eczema patients who had not received Betamethasone in the past

Sex

Number of patients better on Fluocinonide

Number of patients better on Betamethasone

Number of patients equally affected

Male

0

1

5

6

Female

4

0

2

6

Total

4

1

7

12

Total

Table 7 Shows the results in psoriasis patients who had not received Betamethasone in the past

Sex

Number of patients better on Fluocinonide

Number of patients better on Betamethasone

Male

0

2

8

10

Female

1

1

7

9

Total

1

3

15

19

Number of patients equally affected

Total

Tolerance

Discussion

Both topical preparations were well tolerated. Only two patients were reported to have complained of side-effects. A male patient with psoriasis complained of a burning sensation on applying the fluocinonide for­ mulation and another male psoriatic patient reported marked irritation on application of the betamethasone-17-valerate cream.

These results should be viewed with a certain amount of caution as there were relatively small numbers of patients in each group. Superficially, they suggest that the fluocino­ nide formulation was more effective than the betamethasone-17-valerate cream for the treatment of patients with eczema but that there was no appreciable difference in the

fVJ Cunliffe and J Τ Nicholls abilities of the two steroids to benefit patients with psoriasis. This is somewhat in contrast with the findings of other centres where the superiority of the ñuocinonide preparation over betamethasone-17-valerate cream has tended to be more evident in the treatment of psoriatic patients. It is interesting to note, however, that the fluocinonide formulation is only clearly superior to betamethasone-17-valerate in the treatment of those patients who had previously received betamethasone. Both topical steroids were equally effective in the treatment of patients who had not received betamethasone in the past. This finding is not entirely surprising for it is frequently observed in clinical practice that dermatoses may become resistant to the continued use of one particular topical steroid and yet respond to different ones. It would seem, therefore, that in order to compare two topical steroids rigorously, the patients involved should not have received either of the preparations in the past. In this investigation, both the fluocinonide preparation and the cream formulation of betamethasone-17-valerate were well-tolerated. Only one patient on each of the two treatments complained of some skin irritation. It may be concluded that the new steroid formulation, 'Metosyn", is equally effective and acceptable as betamethasone-17-valerate cream in the treatment of patients with eczema or psoriasis who have received neither drug in the past. However, it may well be of therapeutic value for those patients who have failed to respond or have become unresponsive to betamethasone. REFERENCES Baran R (1972) Double-Blind Clinical Trial Comparing Fluocinonide F A P G Cream with Flumethasonc Pivalate Cream. Acta Dermatovener (Suppl 67) 5 2 , 79

75 Binder R & McCleary J (1971) Comparison of Fluocinonide in a DoubleBlind Study with Betamethasone Valerate. Current Therapeutic Research 14, 35 Burdick Κ Η, Poulsen Β & Place V A (1970) Extemporaneous Formulation of Cortico­ steroids for Tropical Usage. Journal of the American Busse Μ J, Hunt P, Lees Κ A, Haggs Ρ Μ D & Medical Association 2 1 1 , 462 McCarthy Τ Μ (1969) Release of Betamethasone Derivatives from Ointments—'In Vivo' and 'In Vitro' Studies. British Journal of Dermatology (Suppl 4) 8 1 , 103 Christie G A & Moore-Robinson Μ (1970) Vehicle Assessment-Methodology and Results. British Journal of Dermatology (Suppl 6) 82, 93 Goldman Μ F, Lockerbie L & Laws Ε A (1971) T h e Evaluation of a N o v e l Corticosteroid Formulation, Fluocinonide in ' F A P G ' Base in the Blanching Test. British Journal of Dermatology 85, 573 KalkofT Κ W (1972) The Activity of Fluocinonide on Diseased and Healthy Skin in Comparison with other Topical Corticosteroids. Acta Dermatovener (Suppl 67) 52, 51 McKenzie A W & Stoughton R Β (1962) Method for Comparing Percutaneous Absorp­ tion of Steroids. Archives of Dermatology 86, 608 Nicholls J Τ (1972) A Multi-Centre Trial of 'Metosyn', a N e w Topical Steroid in a Complex Two-Phase Base. Current Therapeutic Research 14, 259 Portnoy Β & Sarkany I (1972) 'Metosyn' in Psoriasis and Eczema. British Journal of Dermatology 86, 310 Poulsen Β J, Young Ε Coquilla V & Katz Μ (1968) Effect of Topical Vehicle Composition on the 'In Vitro' Release of Fluocinolone Acetonide and its Acetate Ester. Journal of Pharmaceutical Sciences 57, 928 Rosenberg Ε W (1971) Fluocinonide—Preliminary Evaluation of a N e w Topically Applied Corticosteroid. Archives of Dermatology 104, 632 Sarkany I, Hadgraft J W & Baker Β (Unpublished Data) Sarkany I, Hadgraft J W, Caron G A & Barrett C W (1965) T h e R o l e of Vehicles in the Percutaneous Absorption of Corticosteroids—An Experimental and Clinical Study. British Journal of Dermatology 77, 569 Smart J V (1963) The Sign Test. Elements of Medical Statistics 103 Stoughton R Β (1969) Vasoconstrictor Activity and Percutaneous Absorption of Glucocorticosteroids—A Direct C o m ­ parison. Archives of Dermatology 9 9 , 753