Eczematous dermatitis is associated with impairment of epidermal barrier function, leading to increased transepidermal water loss. Patient education regarding proper general skin care is a vital component of treatment success.
This article reports results from a randomized, comparative, 6-week trial evaluating a branded skin cleanser versus a soap-based cleanser in patients undergoing treatment of eczematous dermatitis with clocortolone pivalate 0.1% cream (Cloderm Cream) (n=50).
The duration of treatment ranged from 3 weeks to 8 weeks, depending on response to therapy. A comparison of response to treatment was quantified in both groups using the parameters of change in investigator global assessment and subject global assessment from baseline to study endpoint. Patient preference and skin tolerability data are also reported.
Role of Proper Skin Cleanser and Moisturizer Selection
The importance of proper skin care, especially selecting an appropriate cleanser and moisturizer, is well established in managing eczematous dermatitis.1-3 Although various inflammatory pathways may be triggered during development and progression of specific eczematous dermatoses, such as atopic dermatitis, nummular eczema and asteatotic eczema, epidermal barrier dysfunction is an integral component involved in the pathophysiology of these disorders.3,4 Using appropriate gentle skin cleanser formulations and moisturizers during treatment with prescribed topical medications has been shown to enhance therapeutic response.3,5-8 Proper skin care and moisturizer use may also exert both prophylactic and corticosteroid-sparing effects in patients who have atopic dermatitis and corticosteroid-sparing benefit in patients with psoriasis.8
MVE Formulation as an Advanced SkinCare Technology
Emulsions have characteristically been formulated as two immiscible phases (inner and outer phases), usually oil and water, held together by surface active agents referred to as emulsifiers.
When water comprises the inner phase, the emulsion is classified as water in oil (w/o).
In an oil in water emulsion (o/w), the inner phase is composed of oil. Newer formulation technologies have altered the conventional emulsion systems with the development of water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/0) systems. Additional modifications have resulted in the development of a multiple layer vehicle, which has been applied thus far to cleanser, lotion and cream formulations. This multilamellar emulsion system is referred to as multivesicular emulsion (MVE).9
MVE is composed of concentric layers of multilamellar droplets called vesicles, essentially forming a vehicle comprised of ‘vesicles within vesicles within vesicles and so on’. The patented MVE system allows for one or more ingredients to be incorporated into one (oil or water) or both (oil and water) phases, with potential for controlled release of individual ingredients.9 The MVE system itself has been incorporated into a brand line of skin care products (Cerave) including a hydrating cleanser, moisturizer cream and moisturizer lotion, as well as salicyclic acid 6% cream and lotion (Salex).
The ability of an MVE lotion formulation to reduce transepidermal water loss after epidermal barrier injury as compared to untreated skin has been established. In another study, the MVE hydrating cleanser formulation exhibited a 9% increase in skin hydration
over an 8-hour period after use and rinsing as compared to baseline, with an increase in skin hydration noted within 30 minutes.10
The MVE hydrating cleanser and moisturizer formulations incorporate multiple ceramides (ceramides 1,3,6-11), phytosphingosine (ceramide precursor), cholesterol (lipid), hyaluronic acid (humectant), glycerin (humectant), dimethicone (occlusive, emollient) and petrolatum (occlusive). This article reports results from a randomized, double blind, comparative, open-label 6-week trial evaluating a branded MVE hydrating skin cleanser (Cerave) versus a soap-based cleanser in patients undergoing treatment of eczematous dermatitis with clocortolone pivalate 0.1% cream (Cloderm) twice daily. An additional arm evaluated the impact of an MVE moisturizer cream (Cerave) vs. no treatment in a split-body comparison using a specified target area affected symmetrically at baseline.
A Look at the Study
The objectives of the study were to:
1. Compare the impact of an MVE hydrating cleanser vs. a soap-based cleanser on resolution of signs and symptoms of eczematous dermatitis in patients treated with a mid-potency topical corticosteroid.
2. Evaluate the impact of use of an MVE moisturizer cream vs. no moisturizer use in the same setting.
In the study, the following types of patients were evaluated:
• Adult patients and children ≥5 years of age presenting with eczematous dermatitis diagnosed as atopic dermatitis, nummular eczema or asteatotic eczema rated as mild or moderate severity were included.
The scale used for severity rating required at least a 3 out of 12 based on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) totaling scores for erythema (score of at least 1 required), pruritus (score of at least 1 required), infiltration/papulation and excoriation.
Patients with atopic dermatitis presenting with involvement of the extremities with or without trunk and/or face involvement were included.
Patients who had nummular eczema presenting with involvement of the extremities and/or trunk with at least five discrete areas were included. Where applicable clinically, a potassium hydroxide (KOH) preparation was used to exclude dermatophyte infection.
Patients with asteatotic dermatitis presenting with involvement on the lower extremities were included.
Patients with evidence of secondary infection, those treated with a topical corticosteroid, systemic corticosteroid, topical calcineurin inhibitor or topical antipruritic agent within one week of study entry were excluded.
Patients treated with systemic antihistamines up until the time of entry were included provided the agent(s) were discontinued prior to study initiation and not used throughout the entire study period.
Patients undergoing treatment with immunosuppressive therapies such as cyclosporin, azathioprine (Imuran), systemic tacrolimus (Prograf) and those treated with phototherapy, including use of commercial tanning beds, were excluded.
Patients presenting with any condition determined by the investigator as possibly interfering with study results were excluded.
The trial included three study groups:
• Group 1 (n=22): MVE hydrating cleanser applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area. Regimen completed twice daily (morning and evening).
Average baseline severity score at study entry was 4/12.
• Group 2 (n=20): Soap-based product applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area. Regimen completed twice daily (morning and evening).
Average baseline severity score at study entry was 4/12.
• Group 3 (n=15): MVE hydrating cleanser applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area followed by application of MVE moisturizer cream on one side and no moisturizer cream on the opposite side using designated target areas symmetrically affected at baseline. Regimen completed twice daily (morning and evening). Average baseline severity score at study entry was 5/12.
All patients in groups 1 and 2 were randomized and the investigator and subjects were blinded regarding the cleanser product used. The trial involving the group 3 study arm was investigator blinded. In this study phase, the investigator was blinded as to which side was being actively treated with moisturizer. Side selection was randomized.
Study design indicated a duration of 6 weeks, with patients evaluated at screening, baseline, and at weeks 2, 4 and 6 (+/- 3-day window) for evaluation. All subjects were asked to rate visible clearance (improved, completely gone, worse) of the eruption and response of pruritus (improved, gone, worse) on a daily diary. Parents were allowed to assist children under the age of 12 years.
At any follow-up visit, if the visible eruption and symptoms cleared completely earlier than 6 weeks, the clocortolone pivalate 0.1% cream was discontinued and the designated skincare product(s) (depending on study group) were continued through study endpoint.
Some patients (n=6) were treated for up to 8 weeks as a result of inability to keep their 6-week appointment due to scheduling conflicts. It was determined to not withdraw these six patients as they continued with treatment in accordance with the study protocol.
At study endpoint, all subjects completed a questionnaire related to product preference.
In the group 3 study phase, included were eight patients with atopic dermatitis (upper extremities used as target area for bilateral comparison) and seven patients with either nummular eczema or asteatotic dermatitis (legs used as target area for bilateral comparison).
The age range of included patients was 5 years to 76 years (average age 33 years).
A total of 65 patients were enrolled, with 57 completing the trial (32 females, 25 males); the remainder of the participants were lost to follow-up. Racial distribution was 28 Caucasian, 12 Hispanic, 10 Asian and 7 African-American.The breakdown of included patients by diagnosis was 29 with atopic dermatitis, 17 with nummular eczema and 11 with asteatotic dermatitis. There were no withdrawals or discontinuations related to the reporting of any adverse events.
Assessing Patients’ Treatment Responses
• Investigator global assessment (IGA) was used at each follow-up visit to determine complete clearance, marked improvement, moderate improvement, minimal improvement, no improvement or worsening of the overall visible eruption.
• Subject global assessment (SGA) was used at each follow-up visit to determine complete clearance, marked improvement, moderate improvement, minimal improvement, no improvement or worsening of pruritus.
• Diary responses were evaluated to assess for patterns of response.
• Patient questionnaire on product preference completed at study endpoint.
The study results based on IGA (evaluation of visible eruption) and SGA (evaluation of pruritus) are tabulated in Tables 1 and 2.
Diary Evaluations
As study visits were spaced out over 2-week time periods, IGA and SGA assessment results did not allow for a thorough comparison of rapidity of response separated by study group, especially since all patients were undergoing active topical corticosteroid therapy. Diaries were used to evaluate rapidity of response and were only included if entries were made on at least 80% of total study days.
A review of daily diaries indicated the following results:
• Patients in Group 1 (MVE hydrating cleanser plus clocortolone pivalate 0.1% cream twice daily) demonstrated complete clearance of the visible eruption (redness and rash resolved) an average of 2.6 days faster than patients treated in Group 2 (Soap-based cleanser plus clocortolone pivalate 0.1 % cream twice daily).
• Patients in Group 1 (MVE hydrating cleanser plus clocortolone pivalate 0.1% cream twice daily) demonstrated complete clearance or marked improvement of pruritus an average of 2.2 days faster than patients treated in Group 2 (soap-based cleanser plus clocortolone pivalate 0.1% cream twice daily).
• Among patients in group 3, the sides treated with MVE moisturizer cream completely cleared 3.7 days faster than the sides not treated with the moisturizer. Pruritus completely cleared or markedly improved 3.6 days faster on the moisturizer-treated sides as compared to sides not treated with moisturizer.
Patient Preference
Of the 22 patients in Group 1 and 15 patients in Group 3 who used the MVE hydrating cleanser, 33 of 37 (89.1%) preferred the MVE hydrating cleanser over previously used products. When asked to indicate the primary reason for selecting the MVE hydrating cleanser, the two most common responses related to liking the way the product made the skin feel “soft” or “smooth”.
Points to Remember
• The MVE emulsion system allows for incorporation of several ingredients within vesicles incorporated in concentric lamellar units. This system has been shown with specific formulations to reduce transepidermal water loss and enhance skin hydration.
• The use of a patented MVE hydrating cleanser was shown to enhance therapeutic response when used in combination with a mid-potency topical corticosteroid in patients with atopic dermatitis, nummular eczema and asteatotic dermatitis.
• Based on IGA and SGA assessments, a trend toward more rapid response was observed in the study group using the MVE hydrating cleanser.
• Assessment of daily diaries demonstrated complete clearance of the visible eruption an average of 2.6 days faster, and complete clearance or marked improvement of pruritus an average of 2.2 days faster in patients using the MVE hydrating cleanser as compared to the soap-based cleanser.
• In the side-to-side comparison arm (Group 3), the sides treated with MVE moisturizer cream completely cleared 3.7 days faster than the sides not treated with the MVE moisturizer cream. Pruritus completely cleared or markedly improved 3.6 days faster on the moisturizer-treated sides as compared to sides not treated with the moisturizer.
• The majority of patients utilizing the MVE hydrating cleanser preferred this product over previously used skin cleansers.
Disclosures: Dr. Del Rosso currently serves or has served as a consultant for Coria, Connetics, Galderma, Medicis, Stiefel and Unilever.
Eczematous dermatitis is associated with impairment of epidermal barrier function, leading to increased transepidermal water loss. Patient education regarding proper general skin care is a vital component of treatment success.
This article reports results from a randomized, comparative, 6-week trial evaluating a branded skin cleanser versus a soap-based cleanser in patients undergoing treatment of eczematous dermatitis with clocortolone pivalate 0.1% cream (Cloderm Cream) (n=50).
The duration of treatment ranged from 3 weeks to 8 weeks, depending on response to therapy. A comparison of response to treatment was quantified in both groups using the parameters of change in investigator global assessment and subject global assessment from baseline to study endpoint. Patient preference and skin tolerability data are also reported.
Role of Proper Skin Cleanser and Moisturizer Selection
The importance of proper skin care, especially selecting an appropriate cleanser and moisturizer, is well established in managing eczematous dermatitis.1-3 Although various inflammatory pathways may be triggered during development and progression of specific eczematous dermatoses, such as atopic dermatitis, nummular eczema and asteatotic eczema, epidermal barrier dysfunction is an integral component involved in the pathophysiology of these disorders.3,4 Using appropriate gentle skin cleanser formulations and moisturizers during treatment with prescribed topical medications has been shown to enhance therapeutic response.3,5-8 Proper skin care and moisturizer use may also exert both prophylactic and corticosteroid-sparing effects in patients who have atopic dermatitis and corticosteroid-sparing benefit in patients with psoriasis.8
MVE Formulation as an Advanced SkinCare Technology
Emulsions have characteristically been formulated as two immiscible phases (inner and outer phases), usually oil and water, held together by surface active agents referred to as emulsifiers.
When water comprises the inner phase, the emulsion is classified as water in oil (w/o).
In an oil in water emulsion (o/w), the inner phase is composed of oil. Newer formulation technologies have altered the conventional emulsion systems with the development of water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/0) systems. Additional modifications have resulted in the development of a multiple layer vehicle, which has been applied thus far to cleanser, lotion and cream formulations. This multilamellar emulsion system is referred to as multivesicular emulsion (MVE).9
MVE is composed of concentric layers of multilamellar droplets called vesicles, essentially forming a vehicle comprised of ‘vesicles within vesicles within vesicles and so on’. The patented MVE system allows for one or more ingredients to be incorporated into one (oil or water) or both (oil and water) phases, with potential for controlled release of individual ingredients.9 The MVE system itself has been incorporated into a brand line of skin care products (Cerave) including a hydrating cleanser, moisturizer cream and moisturizer lotion, as well as salicyclic acid 6% cream and lotion (Salex).
The ability of an MVE lotion formulation to reduce transepidermal water loss after epidermal barrier injury as compared to untreated skin has been established. In another study, the MVE hydrating cleanser formulation exhibited a 9% increase in skin hydration
over an 8-hour period after use and rinsing as compared to baseline, with an increase in skin hydration noted within 30 minutes.10
The MVE hydrating cleanser and moisturizer formulations incorporate multiple ceramides (ceramides 1,3,6-11), phytosphingosine (ceramide precursor), cholesterol (lipid), hyaluronic acid (humectant), glycerin (humectant), dimethicone (occlusive, emollient) and petrolatum (occlusive). This article reports results from a randomized, double blind, comparative, open-label 6-week trial evaluating a branded MVE hydrating skin cleanser (Cerave) versus a soap-based cleanser in patients undergoing treatment of eczematous dermatitis with clocortolone pivalate 0.1% cream (Cloderm) twice daily. An additional arm evaluated the impact of an MVE moisturizer cream (Cerave) vs. no treatment in a split-body comparison using a specified target area affected symmetrically at baseline.
A Look at the Study
The objectives of the study were to:
1. Compare the impact of an MVE hydrating cleanser vs. a soap-based cleanser on resolution of signs and symptoms of eczematous dermatitis in patients treated with a mid-potency topical corticosteroid.
2. Evaluate the impact of use of an MVE moisturizer cream vs. no moisturizer use in the same setting.
In the study, the following types of patients were evaluated:
• Adult patients and children ≥5 years of age presenting with eczematous dermatitis diagnosed as atopic dermatitis, nummular eczema or asteatotic eczema rated as mild or moderate severity were included.
The scale used for severity rating required at least a 3 out of 12 based on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) totaling scores for erythema (score of at least 1 required), pruritus (score of at least 1 required), infiltration/papulation and excoriation.
Patients with atopic dermatitis presenting with involvement of the extremities with or without trunk and/or face involvement were included.
Patients who had nummular eczema presenting with involvement of the extremities and/or trunk with at least five discrete areas were included. Where applicable clinically, a potassium hydroxide (KOH) preparation was used to exclude dermatophyte infection.
Patients with asteatotic dermatitis presenting with involvement on the lower extremities were included.
Patients with evidence of secondary infection, those treated with a topical corticosteroid, systemic corticosteroid, topical calcineurin inhibitor or topical antipruritic agent within one week of study entry were excluded.
Patients treated with systemic antihistamines up until the time of entry were included provided the agent(s) were discontinued prior to study initiation and not used throughout the entire study period.
Patients undergoing treatment with immunosuppressive therapies such as cyclosporin, azathioprine (Imuran), systemic tacrolimus (Prograf) and those treated with phototherapy, including use of commercial tanning beds, were excluded.
Patients presenting with any condition determined by the investigator as possibly interfering with study results were excluded.
The trial included three study groups:
• Group 1 (n=22): MVE hydrating cleanser applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area. Regimen completed twice daily (morning and evening).
Average baseline severity score at study entry was 4/12.
• Group 2 (n=20): Soap-based product applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area. Regimen completed twice daily (morning and evening).
Average baseline severity score at study entry was 4/12.
• Group 3 (n=15): MVE hydrating cleanser applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area followed by application of MVE moisturizer cream on one side and no moisturizer cream on the opposite side using designated target areas symmetrically affected at baseline. Regimen completed twice daily (morning and evening). Average baseline severity score at study entry was 5/12.
All patients in groups 1 and 2 were randomized and the investigator and subjects were blinded regarding the cleanser product used. The trial involving the group 3 study arm was investigator blinded. In this study phase, the investigator was blinded as to which side was being actively treated with moisturizer. Side selection was randomized.
Study design indicated a duration of 6 weeks, with patients evaluated at screening, baseline, and at weeks 2, 4 and 6 (+/- 3-day window) for evaluation. All subjects were asked to rate visible clearance (improved, completely gone, worse) of the eruption and response of pruritus (improved, gone, worse) on a daily diary. Parents were allowed to assist children under the age of 12 years.
At any follow-up visit, if the visible eruption and symptoms cleared completely earlier than 6 weeks, the clocortolone pivalate 0.1% cream was discontinued and the designated skincare product(s) (depending on study group) were continued through study endpoint.
Some patients (n=6) were treated for up to 8 weeks as a result of inability to keep their 6-week appointment due to scheduling conflicts. It was determined to not withdraw these six patients as they continued with treatment in accordance with the study protocol.
At study endpoint, all subjects completed a questionnaire related to product preference.
In the group 3 study phase, included were eight patients with atopic dermatitis (upper extremities used as target area for bilateral comparison) and seven patients with either nummular eczema or asteatotic dermatitis (legs used as target area for bilateral comparison).
The age range of included patients was 5 years to 76 years (average age 33 years).
A total of 65 patients were enrolled, with 57 completing the trial (32 females, 25 males); the remainder of the participants were lost to follow-up. Racial distribution was 28 Caucasian, 12 Hispanic, 10 Asian and 7 African-American.The breakdown of included patients by diagnosis was 29 with atopic dermatitis, 17 with nummular eczema and 11 with asteatotic dermatitis. There were no withdrawals or discontinuations related to the reporting of any adverse events.
Assessing Patients’ Treatment Responses
• Investigator global assessment (IGA) was used at each follow-up visit to determine complete clearance, marked improvement, moderate improvement, minimal improvement, no improvement or worsening of the overall visible eruption.
• Subject global assessment (SGA) was used at each follow-up visit to determine complete clearance, marked improvement, moderate improvement, minimal improvement, no improvement or worsening of pruritus.
• Diary responses were evaluated to assess for patterns of response.
• Patient questionnaire on product preference completed at study endpoint.
The study results based on IGA (evaluation of visible eruption) and SGA (evaluation of pruritus) are tabulated in Tables 1 and 2.
Diary Evaluations
As study visits were spaced out over 2-week time periods, IGA and SGA assessment results did not allow for a thorough comparison of rapidity of response separated by study group, especially since all patients were undergoing active topical corticosteroid therapy. Diaries were used to evaluate rapidity of response and were only included if entries were made on at least 80% of total study days.
A review of daily diaries indicated the following results:
• Patients in Group 1 (MVE hydrating cleanser plus clocortolone pivalate 0.1% cream twice daily) demonstrated complete clearance of the visible eruption (redness and rash resolved) an average of 2.6 days faster than patients treated in Group 2 (Soap-based cleanser plus clocortolone pivalate 0.1 % cream twice daily).
• Patients in Group 1 (MVE hydrating cleanser plus clocortolone pivalate 0.1% cream twice daily) demonstrated complete clearance or marked improvement of pruritus an average of 2.2 days faster than patients treated in Group 2 (soap-based cleanser plus clocortolone pivalate 0.1% cream twice daily).
• Among patients in group 3, the sides treated with MVE moisturizer cream completely cleared 3.7 days faster than the sides not treated with the moisturizer. Pruritus completely cleared or markedly improved 3.6 days faster on the moisturizer-treated sides as compared to sides not treated with moisturizer.
Patient Preference
Of the 22 patients in Group 1 and 15 patients in Group 3 who used the MVE hydrating cleanser, 33 of 37 (89.1%) preferred the MVE hydrating cleanser over previously used products. When asked to indicate the primary reason for selecting the MVE hydrating cleanser, the two most common responses related to liking the way the product made the skin feel “soft” or “smooth”.
Points to Remember
• The MVE emulsion system allows for incorporation of several ingredients within vesicles incorporated in concentric lamellar units. This system has been shown with specific formulations to reduce transepidermal water loss and enhance skin hydration.
• The use of a patented MVE hydrating cleanser was shown to enhance therapeutic response when used in combination with a mid-potency topical corticosteroid in patients with atopic dermatitis, nummular eczema and asteatotic dermatitis.
• Based on IGA and SGA assessments, a trend toward more rapid response was observed in the study group using the MVE hydrating cleanser.
• Assessment of daily diaries demonstrated complete clearance of the visible eruption an average of 2.6 days faster, and complete clearance or marked improvement of pruritus an average of 2.2 days faster in patients using the MVE hydrating cleanser as compared to the soap-based cleanser.
• In the side-to-side comparison arm (Group 3), the sides treated with MVE moisturizer cream completely cleared 3.7 days faster than the sides not treated with the MVE moisturizer cream. Pruritus completely cleared or markedly improved 3.6 days faster on the moisturizer-treated sides as compared to sides not treated with the moisturizer.
• The majority of patients utilizing the MVE hydrating cleanser preferred this product over previously used skin cleansers.
Disclosures: Dr. Del Rosso currently serves or has served as a consultant for Coria, Connetics, Galderma, Medicis, Stiefel and Unilever.
Eczematous dermatitis is associated with impairment of epidermal barrier function, leading to increased transepidermal water loss. Patient education regarding proper general skin care is a vital component of treatment success.
This article reports results from a randomized, comparative, 6-week trial evaluating a branded skin cleanser versus a soap-based cleanser in patients undergoing treatment of eczematous dermatitis with clocortolone pivalate 0.1% cream (Cloderm Cream) (n=50).
The duration of treatment ranged from 3 weeks to 8 weeks, depending on response to therapy. A comparison of response to treatment was quantified in both groups using the parameters of change in investigator global assessment and subject global assessment from baseline to study endpoint. Patient preference and skin tolerability data are also reported.
Role of Proper Skin Cleanser and Moisturizer Selection
The importance of proper skin care, especially selecting an appropriate cleanser and moisturizer, is well established in managing eczematous dermatitis.1-3 Although various inflammatory pathways may be triggered during development and progression of specific eczematous dermatoses, such as atopic dermatitis, nummular eczema and asteatotic eczema, epidermal barrier dysfunction is an integral component involved in the pathophysiology of these disorders.3,4 Using appropriate gentle skin cleanser formulations and moisturizers during treatment with prescribed topical medications has been shown to enhance therapeutic response.3,5-8 Proper skin care and moisturizer use may also exert both prophylactic and corticosteroid-sparing effects in patients who have atopic dermatitis and corticosteroid-sparing benefit in patients with psoriasis.8
MVE Formulation as an Advanced SkinCare Technology
Emulsions have characteristically been formulated as two immiscible phases (inner and outer phases), usually oil and water, held together by surface active agents referred to as emulsifiers.
When water comprises the inner phase, the emulsion is classified as water in oil (w/o).
In an oil in water emulsion (o/w), the inner phase is composed of oil. Newer formulation technologies have altered the conventional emulsion systems with the development of water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/0) systems. Additional modifications have resulted in the development of a multiple layer vehicle, which has been applied thus far to cleanser, lotion and cream formulations. This multilamellar emulsion system is referred to as multivesicular emulsion (MVE).9
MVE is composed of concentric layers of multilamellar droplets called vesicles, essentially forming a vehicle comprised of ‘vesicles within vesicles within vesicles and so on’. The patented MVE system allows for one or more ingredients to be incorporated into one (oil or water) or both (oil and water) phases, with potential for controlled release of individual ingredients.9 The MVE system itself has been incorporated into a brand line of skin care products (Cerave) including a hydrating cleanser, moisturizer cream and moisturizer lotion, as well as salicyclic acid 6% cream and lotion (Salex).
The ability of an MVE lotion formulation to reduce transepidermal water loss after epidermal barrier injury as compared to untreated skin has been established. In another study, the MVE hydrating cleanser formulation exhibited a 9% increase in skin hydration
over an 8-hour period after use and rinsing as compared to baseline, with an increase in skin hydration noted within 30 minutes.10
The MVE hydrating cleanser and moisturizer formulations incorporate multiple ceramides (ceramides 1,3,6-11), phytosphingosine (ceramide precursor), cholesterol (lipid), hyaluronic acid (humectant), glycerin (humectant), dimethicone (occlusive, emollient) and petrolatum (occlusive). This article reports results from a randomized, double blind, comparative, open-label 6-week trial evaluating a branded MVE hydrating skin cleanser (Cerave) versus a soap-based cleanser in patients undergoing treatment of eczematous dermatitis with clocortolone pivalate 0.1% cream (Cloderm) twice daily. An additional arm evaluated the impact of an MVE moisturizer cream (Cerave) vs. no treatment in a split-body comparison using a specified target area affected symmetrically at baseline.
A Look at the Study
The objectives of the study were to:
1. Compare the impact of an MVE hydrating cleanser vs. a soap-based cleanser on resolution of signs and symptoms of eczematous dermatitis in patients treated with a mid-potency topical corticosteroid.
2. Evaluate the impact of use of an MVE moisturizer cream vs. no moisturizer use in the same setting.
In the study, the following types of patients were evaluated:
• Adult patients and children ≥5 years of age presenting with eczematous dermatitis diagnosed as atopic dermatitis, nummular eczema or asteatotic eczema rated as mild or moderate severity were included.
The scale used for severity rating required at least a 3 out of 12 based on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) totaling scores for erythema (score of at least 1 required), pruritus (score of at least 1 required), infiltration/papulation and excoriation.
Patients with atopic dermatitis presenting with involvement of the extremities with or without trunk and/or face involvement were included.
Patients who had nummular eczema presenting with involvement of the extremities and/or trunk with at least five discrete areas were included. Where applicable clinically, a potassium hydroxide (KOH) preparation was used to exclude dermatophyte infection.
Patients with asteatotic dermatitis presenting with involvement on the lower extremities were included.
Patients with evidence of secondary infection, those treated with a topical corticosteroid, systemic corticosteroid, topical calcineurin inhibitor or topical antipruritic agent within one week of study entry were excluded.
Patients treated with systemic antihistamines up until the time of entry were included provided the agent(s) were discontinued prior to study initiation and not used throughout the entire study period.
Patients undergoing treatment with immunosuppressive therapies such as cyclosporin, azathioprine (Imuran), systemic tacrolimus (Prograf) and those treated with phototherapy, including use of commercial tanning beds, were excluded.
Patients presenting with any condition determined by the investigator as possibly interfering with study results were excluded.
The trial included three study groups:
• Group 1 (n=22): MVE hydrating cleanser applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area. Regimen completed twice daily (morning and evening).
Average baseline severity score at study entry was 4/12.
• Group 2 (n=20): Soap-based product applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area. Regimen completed twice daily (morning and evening).
Average baseline severity score at study entry was 4/12.
• Group 3 (n=15): MVE hydrating cleanser applied liberally to affected area, gently washed off and patted dry. Clocortolone pivalate 0.1% cream applied and rubbed in gently to affected area followed by application of MVE moisturizer cream on one side and no moisturizer cream on the opposite side using designated target areas symmetrically affected at baseline. Regimen completed twice daily (morning and evening). Average baseline severity score at study entry was 5/12.
All patients in groups 1 and 2 were randomized and the investigator and subjects were blinded regarding the cleanser product used. The trial involving the group 3 study arm was investigator blinded. In this study phase, the investigator was blinded as to which side was being actively treated with moisturizer. Side selection was randomized.
Study design indicated a duration of 6 weeks, with patients evaluated at screening, baseline, and at weeks 2, 4 and 6 (+/- 3-day window) for evaluation. All subjects were asked to rate visible clearance (improved, completely gone, worse) of the eruption and response of pruritus (improved, gone, worse) on a daily diary. Parents were allowed to assist children under the age of 12 years.
At any follow-up visit, if the visible eruption and symptoms cleared completely earlier than 6 weeks, the clocortolone pivalate 0.1% cream was discontinued and the designated skincare product(s) (depending on study group) were continued through study endpoint.
Some patients (n=6) were treated for up to 8 weeks as a result of inability to keep their 6-week appointment due to scheduling conflicts. It was determined to not withdraw these six patients as they continued with treatment in accordance with the study protocol.
At study endpoint, all subjects completed a questionnaire related to product preference.
In the group 3 study phase, included were eight patients with atopic dermatitis (upper extremities used as target area for bilateral comparison) and seven patients with either nummular eczema or asteatotic dermatitis (legs used as target area for bilateral comparison).
The age range of included patients was 5 years to 76 years (average age 33 years).
A total of 65 patients were enrolled, with 57 completing the trial (32 females, 25 males); the remainder of the participants were lost to follow-up. Racial distribution was 28 Caucasian, 12 Hispanic, 10 Asian and 7 African-American.The breakdown of included patients by diagnosis was 29 with atopic dermatitis, 17 with nummular eczema and 11 with asteatotic dermatitis. There were no withdrawals or discontinuations related to the reporting of any adverse events.
Assessing Patients’ Treatment Responses
• Investigator global assessment (IGA) was used at each follow-up visit to determine complete clearance, marked improvement, moderate improvement, minimal improvement, no improvement or worsening of the overall visible eruption.
• Subject global assessment (SGA) was used at each follow-up visit to determine complete clearance, marked improvement, moderate improvement, minimal improvement, no improvement or worsening of pruritus.
• Diary responses were evaluated to assess for patterns of response.
• Patient questionnaire on product preference completed at study endpoint.
The study results based on IGA (evaluation of visible eruption) and SGA (evaluation of pruritus) are tabulated in Tables 1 and 2.
Diary Evaluations
As study visits were spaced out over 2-week time periods, IGA and SGA assessment results did not allow for a thorough comparison of rapidity of response separated by study group, especially since all patients were undergoing active topical corticosteroid therapy. Diaries were used to evaluate rapidity of response and were only included if entries were made on at least 80% of total study days.
A review of daily diaries indicated the following results:
• Patients in Group 1 (MVE hydrating cleanser plus clocortolone pivalate 0.1% cream twice daily) demonstrated complete clearance of the visible eruption (redness and rash resolved) an average of 2.6 days faster than patients treated in Group 2 (Soap-based cleanser plus clocortolone pivalate 0.1 % cream twice daily).
• Patients in Group 1 (MVE hydrating cleanser plus clocortolone pivalate 0.1% cream twice daily) demonstrated complete clearance or marked improvement of pruritus an average of 2.2 days faster than patients treated in Group 2 (soap-based cleanser plus clocortolone pivalate 0.1% cream twice daily).
• Among patients in group 3, the sides treated with MVE moisturizer cream completely cleared 3.7 days faster than the sides not treated with the moisturizer. Pruritus completely cleared or markedly improved 3.6 days faster on the moisturizer-treated sides as compared to sides not treated with moisturizer.
Patient Preference
Of the 22 patients in Group 1 and 15 patients in Group 3 who used the MVE hydrating cleanser, 33 of 37 (89.1%) preferred the MVE hydrating cleanser over previously used products. When asked to indicate the primary reason for selecting the MVE hydrating cleanser, the two most common responses related to liking the way the product made the skin feel “soft” or “smooth”.
Points to Remember
• The MVE emulsion system allows for incorporation of several ingredients within vesicles incorporated in concentric lamellar units. This system has been shown with specific formulations to reduce transepidermal water loss and enhance skin hydration.
• The use of a patented MVE hydrating cleanser was shown to enhance therapeutic response when used in combination with a mid-potency topical corticosteroid in patients with atopic dermatitis, nummular eczema and asteatotic dermatitis.
• Based on IGA and SGA assessments, a trend toward more rapid response was observed in the study group using the MVE hydrating cleanser.
• Assessment of daily diaries demonstrated complete clearance of the visible eruption an average of 2.6 days faster, and complete clearance or marked improvement of pruritus an average of 2.2 days faster in patients using the MVE hydrating cleanser as compared to the soap-based cleanser.
• In the side-to-side comparison arm (Group 3), the sides treated with MVE moisturizer cream completely cleared 3.7 days faster than the sides not treated with the MVE moisturizer cream. Pruritus completely cleared or markedly improved 3.6 days faster on the moisturizer-treated sides as compared to sides not treated with the moisturizer.
• The majority of patients utilizing the MVE hydrating cleanser preferred this product over previously used skin cleansers.
Disclosures: Dr. Del Rosso currently serves or has served as a consultant for Coria, Connetics, Galderma, Medicis, Stiefel and Unilever.
