o5652-u1812-tap ichtyose-dexeryl.indd 1 14/01/09 14:32:51 · ichthyosis is a chronic skin disease...

o5652-U1812-TAP Ichtyose-Dexeryl.indd 1 14/01/09 14:32:51

IntroductionIchthyosis is a chronic skin disease due to a keratinisation disorder and marked by a default of desquamation with skin thickening and extreme dryness. Ichthyosis vulgaris is the most frequent form of the disease. More severe and rarer forms are X-linked reces-sive ichthyosis and non erythrodermic autosomal recessive lamellar ichthyosis (Caputo, 2006). Ichthyosis can be present at birth (congenital ichthyosis) or appear during the first months or years of life. Different classifications have been proposed based on the date of apparition of the lesions, clinical features, histological and ultrastructural aspects of the skin, enzymatic defects and associated extracutaneous clinical signs.

The following forms of the disease are commonly distinguish:• Non-congenital ichthyosis- Ichthyosis vulgaris: dominant autosomic transmission with onset during the first year of life, very frequent (1.5 – 2%), closely genetically linked to atopic dermatitis, characterised by anomalies of keratohyaline granules and a decrease of the stratum granulosum,

- X-linked recessive Ichthyosis: onset at 3 to 6 months of life.• Congenital Ichthyosis- Lamellar Ichthyosis: congenital and rare, characterised by different kinds of ultrastructural changes.- Collodion baby.- Harlequin foetus: very rare and diagnosed at birth, characterised by a thick fixed «cuirass» covering the whole body. If not lethal, the evolution is severe with an erythrodermic Ichthyosis.

The Ichthyosis skin has a dry, rough, scaly and hyperkeratosic aspect. The main cutaneous symptoms of the disease are a severe skin dryness, pruritus and a sweating defect. The dryness is associated to skin discomfort and aesthetic problems. These can have psychological and social repercussions and patients’ and their families’ quality of life can be affected and have to be taken in charge.

As Ichthyosis requires life long treatment, administrated drugs must first be safe and well tolerated. Skin improvement is mainly based on local treatment. Treatment is aimed at decreasing symptoms by providing hydration, lubrication and keratolysis. In the more severe forms of the disease, retinoids (oral or topical) can normalize the process of proliferation and differentiation of keratinocytes.

The proposed medicinal product, DEXERYL® cream, belongs to the class of moisturisers. Moisturisers are wellknown products that are extensively used to improve skin xerosis, i.e. a condition associating a dry and rough skin appearance with the presence of scales at various degree. According to severity, scales may be absent or fine in mild xerosis, of intermediate size and non-adherent in moderate forms, or large and adherent in the most severe forms. Moisturisers are frequently used in ichthyoses, conditions displaying severe xerosis and signs of hyperkeratosis of the skin (Blanchet-Bardon, 2000). Keratolytics are pres-cribed in addition to moisturisers in these conditions.

Classically, three approaches can be used to moisturise the stratum corneum (SC): 1°) humectancy, to help retain water in the skin; 2°) emolliency, to mask the rough scaly condition and soften the skin; and 3°) occlusion, to reduce water loss from the skin and inhibit excessive absorption of cutaneous irritants. Accordingly, moisturisers may be classified as humectants, emollients or barrier creams depending on which of the mechanisms of action of their active ingredients prevail.

By the combination of glycerol (15%) as humectant and emollient, together with vaselin (8%) and liquid paraffin (2%) as occlusive compound, DEXERYL® cream will achieve a moisturising effect through this whole range of actions.


Study ObjectivesThe main objective of this study was to demonstrate the efficacy of a 4-weeks treatment with DEXERYL® cream in reducing the disease severity assessed by a specified symptom sum score SRRC (Scaling Roughness Redness Cracks/fissures score) system on both legs. The primary efficacy criterion was the decrease in SRRC score by at least 50% on the external faces of both legs between baseline and Day 28, the end of the double-blind period.

The secondary objectives were:• To document the maintenance of the efficacy after 12 weeks of treatment• To evaluate the global judgement by the investigator• To evaluate if the product is pleasant to use by the parents and/or the patient• To document the clinical, local and systemic safety over 12 weeks

During the first phase in double-blind, 265 patients under 18 years were treated, after randomization, with DEXERYL® cream, or the vehicle, over the whole body, twice a day for 4 weeks. During the open-label 2nd phase, all the patients were treated with DEXERYL® cream for 8 weeks. The SRRC score was evaluated on two symmetrical areas on the outer side of the legs. The evolution in itching, the number of responsive patients after D28 as well as the overall appreciation of the treatment by the investigator and the patient (or the parents) were secondary evaluation criteria. The local and systemic tolerance were also evaluated.

Material and Methods

Study Design


Baseline CharacteristicsVehiclen = 130

DEXERYL® crèmen = 131

Age (months) 8.52 9.18Sex (% male) 63.1% 67.2%Family history 56.9% 61.1%Lesions at birth 49.2% 53.4%If no, age of first lesions (months) 14.8 17.2Type of ichthyosis:

Vulgaris (%) 81 (62.3) 78 (59.5)X-linked recessive (%) 21 (16.2) 15 (11.5)Lamellar Ichthyosis (%) 15 (11.5) 22 (16.8)Other (%) 13 (10.0) 16 (12.2)

Symptom Score Description

Scaling(visual evaluation)

0 Absent

1 Slight: small scales only, surface lightly dull in colour

2 Moderate: small scales in combination with larger scales (>0.05 mm), surface opaque or whitish

3 Severe: larger and large scales (flakes>1mm) are prominent, surface whitish

4 Extreme: larger flakes covering almost the entire skin surface in the examination field

Roughness(tactile evaluation)

0 Absent: surface perfectly smooth and soft

1 Slight: slightly irregular and scratchy and tangential tactile evaluation

2 Moderate: definitely irregular and cratchy and possibly slightly stiffened on vertical tactile evaluation

3 Severe: advanced irregular and scratchy feeling associated with some stiffening

4 Extreme: gloss irregularity and major disturbance of skin markings and definite stiffening

Redness(visual evaluation)

0 Absent:

1 Slight: small areas of minimal redness or diffuse faint redness

2 Moderate: limited areas of definite redness or diffuse faint and obvious redness

3 Severe: larger areas of definite redness or diffuse and more pronounced redness

4 Extreme: advanced redness in entire examination field (redness of cracks not included)

Cracks fissures(visual evaluation)

0 Absent:

1 Slight: single and superficial cracks in the examination field

2 Moderate: single or grouped superficial and more deep cracks

3 Severe: as 2 but with deep cracks

4 Extreme: dominated by deep cracks

SRRC (Scaling Roughness Redness Craks) ScoreThe SRRC score was the sum of these four symptom grades. The maximum score was 16.


The analysis of the results concerned 231 patients (ITT population), 4 patients were removed from the study prematurely and 30 patients excluded from the analysis (for major deviations from the protocol).

Percentage of patients with a 50% reduction of the SRRC score between D1 to D28 (Scaling, Roughness, Redness, Cracks fissures) Main efficacy criterion

Evolution of the SRRC score from baseline to Day 14 and Day 28 on the external face on the legs

Global evaluation of treatment efficacy by the investigator on Day 28

Results of efficacy of a 4-weeks treatment with DEXERYL® cream in reducing the disease severity

After 4 weeks of double-blind treatment (D28), the percentageof respondent patients was significantly greater in the DEXERYL® cream group than in the vehicle group

A greater efficacy in reducing the disease severity was observed in the DEXERYL® cream group, assessed by a significantlygreater decrease in the specified SRRC score.

The investigator considered the efficacy of treatment with DEXERYL® cream to be satisfying in about 80% of patients (quite satisfying for 42.5% of patients and very satisfying for 35.4% of patients), whereas the efficacy of treatment with vehicle was considered to be satisfying in about one half of patients (quite satisfying for 30.7% of patients and very satisfying for 20.2% of patients).


Evaluation of the SRRC score from baseline to Day 28, 56 and 84 on the external face on the legs in the DEXERYL® cream group (n=116)

Global assessment by the patient and/or the parents after 12 weeks of treatment with DEXERYL® cream

Easiness of use: 95.6% of patients or parents treated with DEXERYL® cream considered the product to be easy or very easy to use

Hydration capacity: in 92.0% of patients treated with DEXERYL® cream the hydration capacity of treatment was considered as good and very good

Evolution of sweating: Patients with ichthyosis have a reduction of sweat glands and a decrease of sweat production. A great percentage of patients or parents, 39.8%, considered sweating to have slightly or very improved with DEXERYL® cream treatment

Maintenance of efficacy after 12 weeks of treatment with DEXERYL® cream

A significant decrease in the SRRC score between Day 28 and Day 56 (p<0.001) and between Day 28 and Day 84 (p<0.001) was noted in the patients treated with DEXERYL®cream

Evolution of pruritus (Visual Analogue Scale) from baseline to Day 28 on the whole body.The decrease in the intensity of pruritus was significantly (p<0.05) greater in the DEXERYL cream group than in vehicle on D14 (-40% versus -25,7%) and on D28 (-58% versus -43,6%).


DEXERYL® cream clinical, local and systemic safety over 12 weeksNumber of Treatment Emergent Adverse Events (TEAE) similar in the DEXERYL® cream group and the Vehicle group. Majority of these TEAE concerned infections and considered to be not related to treatment. During the double-blind period (4 weeks), rare cases of skin disorders (erythema, ur ticaria and skin burning sensation) were observed in DEXERYL® cream group (7 patients) and in vehicle group (5 patients). During the open-label period, 6 cases of skin and subcutaneous disorders including atopic dermatitis, eczema and pruritus, were repor ted in 6 patients of the Vehicle group treated with DEXERYL® cream, no skin reactions were repor ted in the other group.

Overall, the 12-week twice-daily application of DEXERYL® cream to the skin of children induced no systemic and local safety concerns. DEXERYL® cream was thus found to be safe and to have a good tolerability profile.

Overall conclusions

In summary, the overall results confirmed the efficacy of DEXERYL® cream in the symptomatic treatment of ichthyosis in children: higher number of responders with DEXERYL® cream and better improvement of ichthyosis symptoms as skin dryness measured by SRRC and hydration but also pruritus and sweating.

The results of the global evaluation of treatment at the end of the double-blind period were also in favour of DEXERYL® cream.

The safety results indicate that the 12-weeks twice-daily application of DEXERYL® cream to the skin of children induce no systemic and local safety concerns. DEXERYL® cream was thus found to be safe and to have a good tolerability profile.

In conclusion, the results of this multicentre, double blind, randomised and comparative versus vehicle study demonstrated the efficacy of the DEXERYL® cream containing 15% of glycerol, 8% of vaselin and 2% of liquid paraffin in the symptomatic treatment of ichthyosis. The study also showed that the use of DEXERYL® cream is safe in children.

We thank the following persons who contributed to the conduct, analysis or communication of the study:INVESTIGATOR-COORDINATOR: Dr BLANCHET-BARDON Claudine, Hospital Saint Louis, Paris (France).INVESTIGATORS: Dr BUCKOVÁ Hana (CZECH REPUBLIC), Dr RAUDSEPP Heli (ESTONIA), Dr TUOMI Marja-Leena (FINLAND), Pr TRAUPE Heiko (GERMANY), Dr HOGER Peter (GERMANY), Pr FOELSTER-HOLST Regina (GERMANY), Dr THACI Diamant (GERMANY), Dr TADINI Gianluca (ITALY), Pr ANCUPANE Inara (LATVIA), Pr MIKAZANS Ingmars (LATVIA), Dr BALEVICIENE Geromanta (LITHUANIA), Dr VALIUKEVICIENE Skaidra (LITHUANIA), Pr LAKHDAR Hakima (MOROCCO), Pr STEIJLEN Peter Martin (NETHER-LANDS), Pr ORANJE Arnold P. (NETHERLANDS), Pr KASZUBA Andrzej (POLAND), Dr ROSINSKA-BORKOWSKA Danuta (POLAND), Dr DOLYA Olga (RUSSIA), Dr LECHA CARRELERO Marius (SPAIN), Pr DOSS Nejib (TUNISIA).

Results presented during the symposium “skin barrier disorders“ EADV Congress Paris September 2008.

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o5652-u1812-tap ichtyose-dexeryl.indd 1 14/01/09 14:32:51 · ichthyosis is a chronic skin disease...

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