Real-life efficiency and safety comparison study of Calmapherolu S.C ointment based on glycerophosphoinositol (GPI choline) salt of choline and other products in patients with atopic dermatitis.

Summary

Background: Emollients are the first therapeutic line in the treatment of atopic dermatitis (AD) due to their occlusive properties. We have investigated the effectiveness and safety of emollient preparations prescribed in Poland in comparison with emollient ointment containing glycerophosphoinositol salt of choline (GPI).

Methods: We evaluated effectiveness of AD emollient treatment by using scales: Eczema Area and Severity Index (EASI), Three Item Severity (TIS), Visual Analogue Scale (VAS) and Four-item itch questionnaire. 300 patients with moderate AD (according to Rajka and Langeland scale) were stratified into two groups: patients who applied GPIemollient ointment and patients applied other emollient (150 patients in each group).

Results: Statistically significant difference of means in AD symptoms and severity reduction were observed during a control visit after therapy with GPI emollient ointment in comparison with first visit (***p<0,001): itching severity (-1,15 ±0,077), sleep disturbances (-1,56 ± 0,15), TIS (-2,24 ± 0,13), EASI (-13,74 ± 1,14), RL Score (-1,65 ± 0,09) and VAS (-2,49 ± 0,15). Negative values mean that the patient’s health is improving. The group of patients taking a different emollient also obtained statistically significant improvement in AD, however smaller than the group using GPI emollient ointment (***p<0,001).

Conclusion: Emollients show high tolerance among patients and significantly improves their quality of life, previously reduced by symptoms associated with atopic dermatitis, such as persistent pruritus. However, the ointment containing GPI salts was more effective, which shed some light on the potential supportive effect of this ingredient in the treatment of AD.

Keywords: atopic dermatitis, atopic dermatitis therapy, skin care, emollient, Calmapherol SC ointment, SCORAD

Słowa kluczowe: atopowe zapalenie skóry, terapia atopowego zapalenia skóry, pielęgancja skóry, emollient, Calmapherol SC maść, SCORAD.

Monika Marko, Prof. dr hab. n. med. Rafał Pawliczak

Department of Immunopathology, Faculty of Medicine, Medical University of Lodz

Introduction

Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder, affecting both children and adults. AD constitutes a huge social and economic burden, as it can significantly impact the quality of life of affected individuals as well as entire families. It is a disease characterized by complex pathogenesis (1). The key feature of the disease is the fact that it causes defects in skin barrier functions, which lead to drying of the skin. AD typical distinguishing symptoms are, for example, polymorphous skin lesions and intense itch.

The assessment of the severity of AD is based on clinical symptoms and subjective patient feedback. It is an important element of the examination of AD as the determination of the level of its severity allows the choice of the correct therapeutic option and the assessment of treatment’s efficiency, both in everyday practice conditions and clinical trials (2). To assess the severity of AD, we use a range of appropriate measurement scales. Nowadays, we can distinguish over 20 severity measurement scales, which include different aspects of the disease. The most popular measurement scales are SCORAD (Scoring Atopic Dermatitis), EASI (The Eczema Area and Severity Index), TIS (The Three-Item Severity) and VAS (Visual Analogue Scale) (3).

Emollient therapy is considered to be one of the main pillars of AD treatment. In addition to patient education and hygiene, it is an essential part of both disease control and its prevention (4). Emollients and preparation, whose main function is to moisturize the skin by water retention. Emollients create a protective barrier over the skin to lock in moisture, consequently improving the skin appearance and condition and also making it more elastic and soft. It is known that daily emollient care speeds up the formation of proper skin’s barrier, which makes it more resistant to external factors (5). The regular use of an emollient in patients with AD, even if the disease is asymptomatic, relieves dry skin and reduces the risk of exacerbation of the disease by restoring the damaged epidermal barrier and reducing the absorption of irritants and allergens. In cases of the lower severity of AD, emollients used in monotherapy may be enough to control the course of the disease. There is also some evidence that regular use of emollients after withdrawal of topical anti-inflammatory treatment contributes to remission maintenance. Emollients can be found in various creams, ointments, lotions, emulsions, body washes, oils, gels or washing liquids. The knowledge of patients’ preferences can help to choose appropriate preparation, which in consequence increases the efficiency of the therapy (6).

Cosmeceuticals are a new group of topical preparations, whose healing and skin-caring properties are a result of their active ingredients. The aim of cosmeceuticals is not only to restore the epidermis but also to reduce inflammation. The non-steroid Calmapherol S.C. ointment is one of the preparations which combines the features of emollients and anti-inflammatory properties. Some of its ingredients are:

• Glycerophosphoinositol salt of choline ‘GPI choline’ – GPI choline is an innovative active ingredient of plant origin, a lecithin derivative. GPI choline supports the physiological control system. It controls the release of fatty acids responsible for the inflammatory response. It has soothing properties and reduces redness and skin irritation.
• Zinc oxide – Zinc oxide has anti-inflammatory, healing, and regenerating properties. It promotes the healing process of irritations and reduces skin inflammation.
• Vitamin E – Vitamin E helps to hydrate the skin and restore its natural protective functions by preventing moisture loss. It strongly regenerates dry, irritated, and sensitive skin, soothes redness, and eliminates the feeling of tight and rough skin. Its moisturizing properties prevent drying and cracking of the skin.
• Vaseline – Vaseline’s structure creates an occlusive layer over the skin, preventing water evaporation. What is more, it is an emollient, which means that it has softening and soothing properties. 

The purpose of the study: Evaluation of the effectiveness of the emollient preparation Calmapherol S.C ointment and assessment of tolerance of its antipruritic properties in patients with AD.

Additional purpose: Obtaining the information about patients’ satisfaction with the current treatment and their preferences regarding emollient choice, such as consistency, ease of the usage, absorption, efficiency and relieving AD symptoms.

Patients and Methods

The study was an open-ended, non-randomised, real-life, based on doctors’ personal decisions. The study included a group of 300 participants, children and adults aged 1 to 70 with moderate symptoms of AD – classification according to the Rajka and Langeland scale (7). Patients were divided into two groups (150 participants per group): the first was using the preparation Calmapherol S.C ointment while the second was using other emollient recommended by the doctor. Patients were advised to first cleanse and dry the skin surface and then apply the preparation topically and leave it on the skin till fully absorbed at least 2 times a day. Patients’ skin condition was assessed by a dermatologist at the beginning of the study (before the first application of Calmapherol S.C ointment or other emollient) and after 1 month ± 2 weeks since the beginning of the treatment with Calmapherol S.C ointment or other emollient. The changes in the disease progression and its severity, both in children and adults, were assessed basing on the EASI and TIS scales. In order to evaluate pruritus intensity, we used a four-point Pruritus Assessment Questionnaire (according to Szepietowski J., Reich A.), assessing, among other things, sleep disorder, which is one of the symptoms accompanying pruritus in AD. We also subjectively assessed pruritus intensity presented by the VAS scale.

The obtained data was subjected to statistical analysis. Continuous variables were presented as the mean and standard error of the mean (Mean ± SEM). The normal distribution was verified by the Shapiro-Wilk test. The Student’s T-test was used in order to compare continuous variables in two groups, which are both close to normal distribution. Statistical analysis was conducted using GraphPad Prism 8.0 (San Diego, CA, USA).

Results: The skin condition in all patients using Calmapherol S.C ointment was visibly better. There was a statistically significant reduction of AD symptoms after the implementation of topical treatment with Calmapherol S.C ointment. The tables below show the results of comparative analysis of the group of patients using Calmapherol S.C and the second group of patients using other emollients after the first and second doctor’s appointments.

(slide no. 2 from PDF file)

Average difference between 1^st and 2^nd appointment. The obtained results were averaged and presented as the mean ± the standard error of the mean (Mean ± SEM). The statistically significant differences were found at *** p<0,001

(slide no. 14 and 17 from PDF file)

Average difference between 1^st and 2^nd appointment. The obtained results were averaged and presented as the mean ± the standard error of the mean (Mean ± SEM). The statistically significant differences were found at *** p<0,001

(slide no. 9 from PDF file)

Average difference between 1^st and 2^nd appointment. The obtained results were averaged and presented as the mean ± the standard error of the mean (Mean ± SEM). The statistically significant differences were found at * p <0,05

*** p<0,001

Negative values indicate an improvement in the patient’s health state. The higher the negative value, the less symptoms of AD can be observed.

(slide no. 10 from PDF file)

Average difference between 1^st and 2^nd appointment. The obtained results were averaged and presented as the mean ± the standard error of the mean (Mean ± SEM). The statistically significant differences were found at *** p<0,001

Negative values indicate an improvement in the patient’s health state. The higher the negative value, the less symptoms of AD can be observed.

Discussion

The standard treatment regimen for atopic dermatitis (AD) is a combination of emollient therapy with anti-inflammatory therapy (1). There are three therapeutic regimens proposed. The first includes emollients, whereas the second includes topical glucocorticosteroids, tannins and calcineurin inhibitors (2). The third treatment regimen is based on systemic therapy, which is applied to patients who do not show improvement after topical anti-inflammatory therapy (2,3). In the cases of mild to moderate AD, emollients used in monotherapy may be enough to control the disease. Moreover, the regular use of emollients after the withdrawal of topical anti-inflammatory treatment contributes to remission maintenance (4). 

The obtained data provides evidence of the high effectiveness of Calmapherol S.C. Ointment, which significantly improves the skin condition of patients with AD. According to this study, emollient preparations which are available in the Polish market are also able to reduce the symptoms of AD, but to a lesser extent than Calmapherol S.C ointment. The greater effectiveness of Calmapherol S.C emollient ointment is noticeable because of its distinctive ingredients, one of which is Glycerophosphoinositol salt of choline ‘GPI choline’.

GPI choline is an innovative active ingredient of plant origin, a lecithin derivative. GPI choline supports the physiological control system and controls the release of fatty acids responsible for the inflammatory response. It has soothing properties and reduces redness and skin irritation. What is more, it reduces redness and skin irritation (5). Products of plant origin are common ingredients of emollients. The most common are colloidal oats, aloes, shea butter and coconut oil (6). According to Verallo-Rowell et al., (7) and Evangelista et al. (8), coconut oil is able to significantly reduce the severity of AD but is also used due to its antibacterial properties. What is more, in Lisante’s et al. (9) studies, they described the properties of colloidal oats in the treatment of mild and moderate AD in children. In comparison with these common ingredients of plant origin (colloidal oats, coconut oil), GPI salts have not been described so well, which makes it a relatively new ingredient that requires more research. Calmapherol S.C ointment also contains vaseline, which retains moisture in the skin and has the ability to bind and retain water in the corneal layer of the epidermis (6). Czarnowiski et al. (10) described cases in which the skin ‘closed’ by vaseline began the process of restoration of the granular layer and the proper orthokeratosis. An additional ingredient of Calmapherol S.C ointment is zinc oxide, which is used in the treatment of many skin diseases because of its antioxidant, antibacterial and anti-inflammatory properties (11). Faghihi et al. (12) observed a statistically significant improvement in AD patients’ health state after the use of a cream containing 2.5% of zinc sulfate and 0.005% of clobetasol propionate. Similarly, according to the study of Wiegand et al. (13) regarding the use of fabrics coated with zinc oxide in AD treatment, patients showed a significant reduction of AD severity and itching, comparing to the clinical control group. Vaseline and zinc oxide, unlike GPI salt, are common ingredients in many emollients which are available on the pharmaceutical market. Vitamin E is another ingredient of Calmapherol S.C. Vitamin E prevents moisture loss, increases hydration, and restores the natural protective functions of the epidermis. It strongly regenerates dry, irritated, and sensitive skin, and prevents its drying and cracking. Moreover, it soothes redness and eliminates the feeling of tight and rough skin (14). Jaffary et al. (15) in their study reported that vitamin E (400 IU/day) reduced the symptoms of AD (according to SCORAD index) and improved patients’ quality of life, including the insomnia reduction caused by pruritus. 

Emollient preparations available in Poland, compared in this study with Calmapherol S.C ointment, contain ingredients that may cause some side effects in patients with AD. Irritation is more likely to appear in atopic dermatitis. Even lanolin, which is a very common ingredient, can cause intolerance. Some additives used in emollient preparations, such as vitamin C, emulsifiers and detergents, such as sodium lauryl sulfate (SLS) and ethylenediaminetetraacetic acid (EDTA), can also irritate the skin. Contact allergens found in moisturizers include preservatives (parabens), fragrances and emulsifiers (6).

In comparison with commonly used emollients, the ingredients of Calmapherol S.C ointment are efficient and safe to use by patients with AD. Therefore, when choosing an emollient therapy, it is necessary to familiarize yourself with the ingredients of the product, since it determines its therapeutic properties. Basing on the results of this study, it can be said that GPI choline is a promising ingredient that can contribute to the development of emollient therapy of AD. 

Conclusions:

In 2016, our team conducted a similar study on Calmapherol S.C cream (Evaluation of the Effectiveness of Calmapherol S.C in the Treatment of Atopic Dermatitis. The Therapy of Atopic Dermatitis), which also has in its composition an innovative ingredient – GPI choline salt. The purpose of our previous study was to evaluate the effectiveness of Calmapherol S.C in the treatment of AD using a clinical tool for assessing the severity of atopic dermatitis – SCORAD.

Our latest study was extended in order to compare the effectiveness of another preparation containing GPI choline – Calmapherol S.C ointment with other emollients, which are already used in Poland for AD symptoms. In this study, we applied other scales to assess the severity of AD, such as TIS, VAS and ESI. Similarly, as in our previous study, the results of this study indicated a significant improvement of AD patients’ health state after the treatment with Calmapherol S. C ointment in all test scales.

The group of patients applying other emollients also experienced an improvement, but to a lesser extent than the group using Calmapherol S.C ointment. Patients of the study followed recommendations regarding the dose and regularity when experiencing severe AD symptoms. While the symptoms were abating, a significant number of patients (in both groups) were omitting the recommended dose. According to patients, the most important feature of emollient preparation is its effectiveness in alleviating the symptoms of AD. Then there are characteristics such as the product’s efficiency and its absorption.

The results of this study confirm that the preparation Calmapherol S.C ointment is effective in the treatment of AD due to its innovative (GPI choline salt) and rich composition and proves high tolerance among patients, both children and adults. This preparation significantly improves patients’ quality of life, previously reduced by AD symptoms such as insistent itch. The study showed that Calmapherol S.C ointment is also able to reduce sleep disorders caused by pruritus. The results prove the validity of the usage of Calmapherol S.C ointment in the treatment of AD symptoms. An important aspect in assessing the effectiveness of an emollient preparation is the observance of recommendations such as systematicity since it has a large impact on the effectiveness of therapy. This study suggests that we should pay greater attention to increasing patients’ awareness regarding the correct usage of emollients, which may increase the effectiveness of AD treatment. When choosing emollient therapy, doctors should be governed not only by the effectiveness of the drug but also by the patient’s preferences. The obtained data indicates that Calmapherol S.C ointment, in addition to its effectiveness in alleviating the symptoms of AD, also showed high patients’ tolerance and satisfaction with the therapy. 

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