Influence of the cream with filaggrin activity modulator for dry and sensitive skin in children with mild to moderate severity atopic dermatitis on objective indicators of skin barrier function and disease severity indices

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Atopic dermatitis (AD) is a heterogeneous relapsing skin disease that occurs in childhood and adulthood. Although atopic dermatitis is a chronic skin condition, some children grow out of it at some point in their lives and may go into long-term remission. The reported age-standardized prevalence by age group, based on data from the Global Atopic Dermatitis Report 2022, shows a bimodal curve, suggesting a high prevalence of atopic dermatitis in young children that declines into adulthood with an upward trend in later life . One of the main functions of the skin is to act as a barrier between the person and the environment, preventing water loss while preventing the entry of pathogens and allergens. Dysfunction of the skin barrier is a key clinical feature of atopic dermatitis, as it promotes allergen penetration, immunological dysfunction and, as a result, an increased risk of developing eczema. Dysfunction of the skin barrier has been associated with the etiology of the itching (pain)-scratch cycle [1]. Filaggrin protein plays a significant role in maintaining the protective function of the skin barrier, in particular maintaining pH, hydration and antimicrobial functions. Filaggrin is a multifunctional, histidine-rich, insoluble protein. Filaggrin deficiency has been associated with various dermal (eg, ichthyosis vulgaris, allergic contact dermatitis) and non-cutaneous (eg, diabetes, inflammatory conditions of the gastrointestinal tract, peanut allergy) disorders and may result from genetic, immunological, and environmental factors [ 2].
Steinert and Dale named this protein "filaggrin" in 1981 because of its ability to aggregate keratin intermediate filaments. (f'illaggrin, filament aggregating protein). In 1991, the human profilaggrin progenitor gene was reported to encode 10, 11, or 12 nearly identical repeats. Fewer monomers in profilaggrin (i.e. 10 versus 12) creates an increased risk of developing atopic dermatitis. Notably, mouse and rat genes encode up to 20 repeats. The lifetime of filaggrin is the time required for keratinocytes of the granular layer to move to the inner stratum corneum. During this transition, filaggrin promotes the transformation of corneocytes into "building blocks" that become an impenetrable surface barrier. The subsequent degradation of filaggrin is as remarkable as its synthesis, and the end products help maintain the moisture content of the stratum corneum [3]. It has been shown that genes encoding skin barrier proteins determine the role of heredity in the development of AD [1].

There is increasing experimental, genetic and clinical evidence of AD as a prerequisite for the subsequent development of other atopic diseases such as asthma, food allergies and allergic rhinitis. This situation is called "atopic march".
According to a Russian study [5], polymorphism of the filaggrin gene is associated with AD in women in the Caucasoid population of Central Russia. Bioinformatic analysis predicted that filaggrin gene (FLG) SNPs have epigenetic and non-synonymous effects, are involved in the control of gene expression and alternative splicing of genes that contribute to the pathophysiology of AD.
Another property of filaggrin is its ability to limit the growth of Staphylococcus aureus, ensuring the normal composition of the skin microbiome and maintaining the physiological level of epidermal acidity [6, 7].
In addition, features of the microbiome of affected and healthy skin correlate with the severity of the disease, suggesting a possible link between the skin microbiome and host genetics. In a case-control study, alpha microbiome diversity was lower in patients with AD compared with controls in healthy skin (effect size, 0.710; 95% CI, 0.27–1.15; P = .002), affected skin (effect size, 0.728; 95% CI, 0.35–1.33; P = 0.001) and on the nose (effect size, 1.111; 95% CI, 0.48–0.94; P < 001). Alpha diversity was inversely correlated with disease severity for affected skin (effect size, 0.530; 95% CI, 0.23–1.64; P = 0.02) and skin without lesions (effect size, 0.451; 95% CI, 0 .04-2.44; P = 0.04) in patients with AD. The composition of the skin microbiome without AD lesions has been associated with filaggrin gene mutations [8].
The results of the analysis of filaggrin gene mutations are consistent with a recently proposed unifying hypothesis that offers a mechanistic understanding of the pathogenesis of eczema, synthesizing a hereditary defect in the epithelial barrier and, as a result, weakening of epidermal defense mechanisms against allergens and microbes, followed by polarized T(H)2-lymphocytic responses followed by chronic inflammation involving autoimmune mechanisms. Although strong evidence from FLG genetic studies indicates that barrier dysfunction plays a key role in the pathogenesis of eczema in most patients, much is still unknown about the sequence of biological, physicochemical, and aberrant regulatory events that represent the transition from an inherited barrier defect to the clinical manifestations of inflammatory diseases. eczematous lesions and predisposition to concomitant atopic disorders. The exact contribution of FLG to the wider atopic history, factors that modify FLG expression, and the role of other barrier proteins remain to be determined [9]. However, it is already clear that attempts to activate filaggrin may represent an important pathway for affecting AD.

The basis of the treatment of atopic dermatitis are effective mitigating regimens [10]. A comprehensive review of 14 independent published clinical guidelines from around the world (US, UK, Europe, Japan, Korea, Singapore, Canada, South Africa and selected European countries) showed that daily moisturizing and softening is the general recommendation for the treatment of AD [11].
An emollient is defined as any substance that softens the skin by slowing down the evaporation of water. Sesame, almond and olive oils have been used since ancient Egypt; beeswax, spermaceti, almond oil, borax and rose water - in Ancient Greece; lanolin (sheep fat) - in medieval Europe. Modern emollients include petroleum jelly, zinc oxide, paraffin, mineral oil (liquid mixtures of high-boiling (high molecular weight) hydrocarbons), glycerin, beeswax, olive oil, coconut oil, lanolin, cocoa butter, and synthetics such as butyl stearate and diglycol laurate.
Strictly speaking, the concept of an emollient combines products that include three groups of substances [7] or some combination of them. The first group includes substances that create a hydrophobic barrier - a waterproof film - on the skin (occlusive agents, vegetable and mineral oils and their components), which reduces transepidermal water loss. Humectants can increase the transport of moisture from the dermis to the epidermis, from the deep/mid layers of the epidermis to the surface, and in humid conditions they also help the stratum corneum absorb water f.rom the external environment. The most commonly used substances in this group are glycerin, hyaluronic acid and urea. The third group of substances, usually lipids and carbohydrates, filling the gaps between groups of corneocytes, but not creating a pronounced occlusive effect, are called emollients. Examples of such substances are ceramides, cholesterol, octyloctanoate, propylene glycol and isopropyl palmitate. Sometimes the term "emollient" refers to all emollients, so in this paper the terms emollients/moisturizers and emollients will be used interchangeably.

Recently, more and more attention has been paid to emollients, in which, to improve their properties, additional components are used [12], for example, filaggrin activity modulators (“emollients plus”). These products include a cream for dry, sensitive and atopic-prone skin with a modulator of Admer's filaggrin activity. Admer's cream contains filagrinol 5%, ceramide PC-104-1%, 18 β-glycyrrhetinic acid -1%, niacinamide - 4%, glycerol -4%, natural oils (shea, mango, cocoa, aloe). Filaggrinol is a modulator of filaggrin activity, which is a complex of unsaponifiable fractions of soybean, olive, wheat germ oils and pollen extract of an ethnomophilic plant (with low allergenic potential).
In a clinical study [13], it was demonstrated that this cream is highly effective and safe when used as a moisturizer for AD - four weeks of therapy leads to a decrease in the severity of the manifestations and severity of AD, a decrease in the intensity of itching, and an increase in the level of skin hydration.
Goal and tasks
The aim of the study was to study the effect of a cream for dry, sensitive and atopic-prone skin with a modulator of filaggrin activity (Admera) on mild to moderate AD.
To achieve this goal, the following tasks were set: to assess the dynamics of changes in the severity of AD during treatment when using a cream for dry and sensitive skin with a modulator of filaggrin activity as part of complex therapy; evaluate the dynamics of transepidermal water loss and skin pH; analyze the assessment by patients and / or their legal representatives of the organoleptic properties and ease of use of the drug, as well as the safety of the care product.
Materials and methods
An open, prospective, multicenter, non-comparative, single-group clinical study was conducted on the efficacy and safety of a cream with Admer's filaggrin activity modulator as part of complex therapy. The study was conducted in outpatient visit settings at 3 clinical centers and included 5 visits of which visit 1 was a screening visit and visit 5 was a follow-up visit. The application of the study cosmetic product was carried out for 84+/-2 days, i.e. lasted 12 weeks, which is much longer than the previously described Russian study [13].
Patients applied Admer's cream to the affected areas of the skin, surrounding their skin, and skin with signs of dryness. The cream should be applied in a thin layer on well-cleansed and dry skin, rubbing lightly, at least once a day. If necessary, you can use the product more often to maintain skin hydration. The cream should also be applied after taking hygiene procedures (bathing, shower). The frequency of application of the product is consistent with the recommended frequency of application of emollients in atopic dermatitis [14].

The study included male and female patients, aged 3 to 18 years inclusive, diagnosed with mild to moderate atopic dermatitis. The inclusion criteria were a confirmed (based on the Hanifin and Rajka criteria [15]) diagnosis of AD with a SCORAD score of less than 50 and that met all additional eligibility criteria for the study:
1. Availability of a signed Study Participant Information Sheet (for parents/adoptive parents) with an informed consent form to participate in the study.
2. Male and female patients aged 3 to 18 years inclusive.
3. Stage of atopic dermatitis: the stage of pronounced clinical manifestations (exacerbation period) without weeping and secondary infiltration of the skin or the stage of incomplete remission (the disease is controlled, but there are small lesions in the form of infiltration, lichenification, dry skin).
4. The prevalence of the skin process: a limited localized process.
5. Clinical and morphological forms of atopic dermatitis: exudative or erythematous-squamous or erythematous-squamous with lichenification or lichenoid.
6. Uncomplicated form of atopic dermatitis.
7. Patients with no or presence of sensitization: food, fungal, tick / household, pollen.
8. Outpatients with clinical manifestations of atopic dermatitis who require therapy with topical corticosteroids (mometasone furoate) in a topical cream dosage form and require the use of moisturizers.
At the screening stage, 60 patients were included in the study, of which 60 patients were allowed to use the study drug, 60 patients completed the study in accordance with the protocol.
The study tested the hypothesis of a significant improvement in the SCORAD score after application of the study cosmetic product relative to baseline after 12 weeks (84 days) of therapy.
Additionally, the dynamics of the total SCORAD index after 14, 28 and 56 days of therapy, EASI , IGA indices, transepidermal water loss (TEWL), changes in skin pH, xerosis intensity after 14, 28, 56 and 84 days of therapy compared with the initial value were evaluated.
TEWL < 25 g/h•m2 and skin pH 4.5-5.5 were used as reference values.

The severity of the disease was established based on the value of the SCORAD index [16]: mild - less than 25 points, moderate - from 25 to 50 points, severe - more than 50 points. The EASI score ranges from 0 to 72 [17]. 0 indicates clear skin or no eczema, 0.1 to 1.0 indicates almost no eczema, 1.1 to 7 indicates mild disease, 7.1 to 21 indicates moderate disease, 21 1 to 50 indicates severe disease and greater than 51 indicates very severe disease.
As auxiliary indicators, the SCORAD 25, SCORAD 50, SCORAD75 and SCORAD 100 indices were calculated, which means an improvement in scores by 25, 50, 75 and 100%, respectively. In addition, similar indices were calculated for EASI, IGA, VAS scores for xerosis, TEWL changes, and pH.
For statistical data analysis, non-parametric statistics methods were used due to the semi-quantitative nature of a number of variables. Statistical processing of the results included the calculation of the median of changes in the values of quantitative indicators and their interquartile distance, as well as the assessment of the median and interquartile distances for visits. To assess the significance of changes between the first and fifth visits, the scores were compared using a paired Wilcoxon test. When conducting a qualitative assessment of objective indicators of the barrier function of the skin and global indices, the proportion of patients in certain groups was calculated and the exact 95% confidence interval for the proportion (Clopper-Pearson) was calculated. A Type I error rate of 5% was chosen as the cutoff for deciding whether to reject the null hypothesis of no significant change or difference in proportions (i.e., p<0.05 was required to reject the null hypothesis). Statistical data processing was performed in the R system (version 3.5).

Results
The main results of assessing changes in measured indicators during the study are shown in Table 1.
Table 1. Change in the main indicators during the treatment period
Score Median (IQR) Median change visit 5-1 (IQR) p by Wilcoxon test
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5
SCORAD 25.1 (9.5) 18.4 (11.4) 12.2 (9.3) 7.65 (9.4) 3.9 (8.8) -19.6 (9.75) <0.001
EASI 4.0 (3.5) 3.0 (2.0) 1.5 (1.0) 1.0 (1.0) 1.0 (1.0) -3.0 (4.0) <0.001
IGA 2.0 (1.0) 2.0 (1.0) 2.0 (1.0) 1.0 (1.0) 1.0 (1.0) -2.0 (1.0) <0.001
VAS-K 4.0 (1.5) 3.0 (2.0) 2.0 (1.0) 2.0 (2.0) 1.0 (2.0) -3.0 (2.0) 0) <0.001
TEWL (vapometry, g/h•m2) 9.0 (7.88) 7.50 (6.50) 6.75 (4.50) 5.63 (1.88) 4.25 (1.25) -4.5 (8.8) <0.001
pH 5.41 (0.40) 5.40 (0.41) 5.45 (0.31) 5.55 (0.47) 5.38 (0.38) 0.02 (0.54) 0.337
Note: IQR - interquartile distance
As can be seen in the table, the total score on the SCORAD scale began to decline quite quickly, by the third visit the median value was two times lower than the initial value. At visit 5, the median was only 3.9 versus 25.1 at baseline. The overall decrease (median) was 19.6 points and it was significant (p<0.001) (Fig. 1).

Figure 1. Dynamics of the median value of the total score of the SCORAD index.
When analyzing the dynamics of the “A” (“lesion area”) SCORAD index, statistically significant differences compared to baseline were already achieved on the 14th day of therapy (Visit 2, p=0.001) and persisted (p<0.001) until the end therapy (Visit 5) both in the area of the anterior surface of the head and in other localizations in the aggregate. Thus, the average value of the area of the lesion in assessing the anterior surface of the head according to SCORAD at screening was 0.55 ± 0.78, at Visit 2 - 0.383 ± 0.563, at the third visit - 0.275 ± 0.499, at the fourth visit - 0.097 ± 0.269, and at fifth visit - 0.05 ± 0.2%.
Of additional interest was the assessment of the total SCORAD score and its index "A" in relation to the area of the anterior surface of the head and other localizations in children who did not use mometasone furoate during the study. The number of children who did not need mometasone furoate in this study was 43. In the non-mometasone furoate population, the mean SCORAD score at the Screening visit (Visit 1) was 26.649 ± 10.941, after 14 days of therapy it was 20.958 ± 10.062, after 28 days 15.607 ± 10.723, after 56 days 11.38 ± 10.14, after 84 days - 7.474 ± 9.329. The values of the total index obtained after 14, 28, 56 and 84 days of therapy were statistically significantly lower than the values obtained at baseline (p < 0.001). A similar situation with improvement already from the 2nd week of therapy until the end of the study was noted when assessing the area of damage to the anterior surface of the head, as well as in all other localizations in children who did not receive mometasone furoate (p<0.001).

Percentage improvement of the total SCORAD index - the achievement of a certain percentage of improvement is illustrated in Fig.2.
Figure 2. Percentage improvement in the SCORAD index at visits 2 to 5. The designation SCORAD99 means the index SCORAD 100.
As can be seen in this figure, by the second visit, a 25% improvement (at least) was observed in half of the participants, only 1.7% had a 50% improvement. At the third visit, there is already an improvement of 75% (in 5%) and even 100% (in 3.3%). By the fourth visit, an improvement of at least 25% was observed in almost all study participants. At the same time, 15% showed an improvement in the index by 100% or more. By the 5th visit, there were already almost 42% of such patients.

Another index that assesses the severity of AD and was used in the study was the EASI index. As can be seen in Table 1, the EASI score significantly decreased, amounting to 3 points at the second visit and 1 point at visits 4 and 5 (p<0.001). The initial median value of the EASI index at the first visit was 4, the dynamics of the median value of assessing the severity and prevalence of AD according to the EASI index is shown in Fig. 3.
Figure 3. Dynamics of the median value of assessing the severity and prevalence of AD according to the EASI index.
Percentage improvement of the index - achievement of a certain percentage of improvement is illustrated in Figure 4.

Figure 4. Percentage improvement in the EASI index at visits 2 to 5. The EASI99 designation stands for the EASI 100 index.

As can be seen in the figure, an improvement of 25% was achieved in 63% of patients already at the second visit. In a third of patients, the index improved by 50% or more. By the third visit, 73% improved by 50% or more, and 5% improved by 100%. By the end of the study (visit 5), 100% improvement was observed in 48%, and 75% - in three quarters (77%) of all examined.
Assessment of the severity of atopic dermatitis, carried out by the IGA index (Table 1), showed that at screening the median score on this scale was 2 points, although the initial median IGA was 2 points. The fact that the median reduction in IGA was 2 points, but was not 0 at visit 5, suggests a greater reduction in the global score at higher baseline IGA values. The reduction in IGA was statistically significant (p<0.001). Visually, percentage changes by visits are shown in fig. 5.

Figure 5. Percentage improvement in the IGA Global Score Index at visits 2 to 5. The IGA99 designation stands for the IGA 100 index.
As can be seen in the figure, by the second visit, an improvement of 25% was observed in 17% of those examined. By the third visit, a 25% improvement was reported in 58%, and 27% had a 50% improvement. An improvement of 75% and 100% was noted in only 3.3%. However, by the fourth visit, the percentage of improvement by 100% rose to 15%, an improvement of 25% was noted in 80% and 50% in 58.3%. At the final visit, IGA improvement of at least 25% was seen in 92% of patients and 50% improvement in 80%. A 100% improvement was observed in 42%, but it should be noted that with a limited range of IGA scores, it was difficult to achieve a 100% improvement.
Evaluation of xerosis intensity, carried out on an 11-point VAS (from 0 to 10 points), showed that the initial median VAS score was 4.0 (Table 1), at the second visit it was one point less, at the third - two points less and the median VAS at the last visit was 1, with a median decrease of 3 points over the follow-up period (p<0.001). The percentage change in VAS by visits is shown in fig. 6.
Figure 6. Percentage improvement in VAS xerosis intensity scores at visits 2 to 5. The designation VAS99 means a VAS score of 100.
As can be seen in the figure, by the second visit, an improvement of 25% was registered in 52% of patients, although no one had an improvement of 75% or 100%. At the third visit, an improvement on the VAS scale by 75% was noted in 13.3%, and by 100% - in 5%. At the same time, a 25% improvement was noted by 83% of the participants, and by 50% - 52% of the examined. By the fourth visit, 50% improvement rose to 73%, 75% improvement was in 38% of participants and 100% or more percent in 27%. At the last visit, an improvement of at least 25% was observed in almost all - 92% of patients, an improvement of 75% was noted in 64% of participants and a 100% improvement was observed in 47%. At the same time, the initial severity of xerosis according to VAS was not very high, which means that it was difficult to achieve a high percentage reduction.
Assessment of skin hydration on the cheeks showed a statistically significant decrease in the TEWL index compared to the baseline, starting from the 2nd week of therapy (14 days) and further until the end of therapy (84 days) (at all visits, p < 0.001): at screening, the index was 10.95 ± 5.444 g/m2/h, after 14 days – 9.033 ± 4.69 g/m2/h, after 28 days – 7.867 ± 3.735 g/m2/h, after 56 days – 6.083 ± 2.142 g/m2/h h, after 84 days - 4.433 ± 1.047 g/m2/h (Fig. 7). A statistically significant increase in the level of skin hydration in the T-zone compared to baseline was also found from the 2nd week of therapy (14 days) until the end of therapy (84 days) (for all visits, p < 0.001).

Figure 7. Dynamics of the values of the indicator for assessing the level of skin hydration by the index of transepidermal water loss using vaporimetry (g/m2/h) throughout the study.

The evaluation of the averaged data on TEWL is given in Table. 1. As can be seen in this table, water loss decreased from 9 g/h/m2 at the first visit to 4.25 g/h/m2 at the fifth visit. The decrease in average water loss indicators was fairly uniform from visit to visit, amounting to about 1.5 g/h/m2, the total decrease in water loss was 4.5 g/h/m2 and was statistically highly significant (p<0.001). Dichotomized percentage changes in TEWL are shown in fig. 8.
Figure 8. Percentage improvement in TEWL scores at visits 2 to 5. The designation TEPV99 means an improvement of TEPV 100.
As can be seen in this figure, the best situation was with a decrease in TEWL by 25%. Already at the third visit, an improvement of 25% was observed in 60% of patients, and by the fourth visit, such an improvement was already in 90% and at the fifth it was equal to 92% of all patients. In other words, the use of a cream with a filaggrin activity modulator resulted in an improvement in the barrier function of the skin in almost all patients, but mostly not very pronounced. By the fifth visit, an improvement of 50% or more was observed in 57% of patients, and 75% in 24% of patients.
However, in this group of patients, a significant change in TEWL was not expected, since the estimates of water loss were quite low and, as can be seen in Table 2, no one had significant water loss since the first visit.
In contrast to AD severity indices and TEWL, changes in skin pH could not be detected, as pH was within the normal range at baseline. When applying Admer's cream, a shift to the alkaline side was not observed. As can be seen in Table 1, the pH varied from visit to visit not very pronounced, with median values within the normal range of about 5.4 at a rate of 4.5-5.5.

Table 2. Qualitative assessment of objective indicators of skin barrier function and global indices by visits
Rate % (n) 95% CI
Visit
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5
TEWL (increased) 0 (0) 0…6.0 0 (0) 0…6.0 0 (0) 0…6.0 0 (0) 0…6.0 0 (0) 0…6.0
pH (deviations from the norm) 38.3 (23) 26.1…51.8 45.0 (27) 32.1…58.4 35.0 (21) 23.1…48.4 53.3 (32 ) 40.0…66.3 36.7 (22) 24.6…50.1
SCORAD (>25) 50.0 (30) 36.8…63.2 25.0 (15) 14.7…37.9 15.0 (9) 7.1…26.6 8.3 (5) 2.8…18.4 6.7 (4) 1.9…16.2
EASI (>1) 91.7 (55) 81.6..97.2 81.7 (49) 69.6…90.5 50.0 (30) 36.8…63.2 26.7 (16 ) 16.1…39.7 13.3 (8) 5.9…24.6
IGA (>1) 91.7 (55) 81.6…97.2 90.0 (54) 79.5…96.2 71.7 (43) 58.6…82.6 41.7 (25) 29.1…55.1 20.0 (12) 10.8…32.3

Very good dynamics was observed for AD severity indices. As can be seen in Table 2, at the first visit, the average severity of AD (more than 25 points of the SCORAD index) was observed in 50% of the examined (95% CI = 36.8...63.2%). However, after 14 days of therapy (second visit), the number of people with moderate AD decreased by half - to 25% (95% CI = 14.7...37.9%). Considering the fact that the upper limit of the confidence interval was lower than the estimate of the proportion of patients with moderate AD before the start of therapy, one could speak of a significant decrease in the number of patients with moderate severity and its transition to mild severity. By the third visit, moderate disease remained only in 15% of the examined patients, and at the final visit, AD of moderate severity according to the SCORAD index was detected only in 4 people (6.7%, 95% CI=1.9...16.2 %). EASI index values of more than one point at the first visit were noted in 92% of the entire group of examined patients (95% CI=81.6...97.2%). By the third visit, only half of such persons remained (95% CI = 36.8...63.2%), a significant decrease, judging by non-overlapping confidence intervals. At the last, fifth, visit, only 8 people had EASI values of more than one point (13.3%, 95% CI = 5.9 ... 24.6%) - also a significant decrease not only in comparison with the first, but also third visits. The IGA global assessment index has undergone similar dynamics. Its values of more than one point at the first visit were noted in 92% of the study participants (95% CI=81.6...97.2%). However, a pronounced decrease occurred only by the fourth visit (41.7%, 95% CI=29.1...55.2%). At the last, fifth, visit, the proportion of people with IGA more than one point was 20% (95% CI=10.8...32.3). Thus, the use of a cream with a modulator of filaggrin activity as part of standard therapy led to an improvement in the course of AD in terms of severity and prevalence of the process, the degree of violation of the skin barrier function according to vapometry in this group was not significantly impaired, but there was no close relationship between therapy and skin pH observed.

Next, an assessment was made of overall satisfaction with the use of the cream and satisfaction with its organoleptic properties. The results are shown in Table 3, since the vast majority gave the highest rating, data are given only for it.
Table 3. Assessment of satisfaction with the use of the cream, 5-point scale
Indicator Score n/N Percentage 95%CI
Satisfaction score on the Likert scale, points 5 - Excellent 53/60 88.30% 77.4…95.2%
Smell rating 5 - Like it very much 52/60 86.70% 75.4…94.1%
Texture/consistency score 5 - Like it very much 50/60 83.30% 71.5…91.7%

An excellent score on the Likert scale was given by 88.3% of all respondents (Fig. 9). The smell was rated with the highest rating - “very much” - by 86.7% of all respondents (Fig. 10), and they noted that they liked the texture/consistency very much - 83.3% of respondents (Fig. 11). Only one person, when asked about the organoleptic properties of the cream, chose the rating "acceptable", all the rest, who did not choose the highest score, indicated the rating "like".
Figure 9. Evaluation of the effectiveness of the use of a cosmetic product on a 5-point Likert scale by parents/adoptive parents of patients on day 84±2 of therapy.


Figure 10. Evaluation of the organoleptic properties of a cosmetic product - smell.

Figure 11. Evaluation of the organoleptic properties of a cosmetic product - texture.
The result of the good tolerability of the cream was a high adherence to therapy (compliance). It did not fall below 98% (one person), while, respectively, both the median and the mode were equal to 100%.

Conclusion
Thus, the study found a significant improvement in the condition of children of different age groups with mild to moderate atopic dermatitis after 12 weeks of using Admer cream as part of standard therapy compared with the baseline. The results of the efficacy evaluation showed that 12-week therapy with Admer's cream leads to a decrease in the severity and severity of atopic dermatitis, a decrease in the intensity of xerosis, an increase in the level of skin hydration and maintaining pH within the physiological norm. It should be noted that the effectiveness of therapy in terms of reducing the prevalence and severity of atopic dermatitis (SCORAD and EASI scales), reducing the intensity of xerosis (VAS scale) and increasing the level of skin hydration (TEWL index), while a significant improvement was noted both when applied to the face and and when used on other parts of the body. Of additional interest was the assessment of the total SCORAD score in children who did not use mometasone furoate during the study. The mean value of the total score of the SCORAD index by the fifth visit decreased by 72% in this observation group. The decrease in the severity and severity of atopic dermatitis established in the study indicates an improvement in the quality of life of patients. With long-term regular use, the results became significantly better than with short-term use. Throughout the study, the study cosmetic product was well tolerated by patients. No adverse events were reported during the present study. As a result of the study, it was found that Admer's cream showed high efficiency, good tolerance and can be recommended to patients with AD as a basic care product.

Conflict of Interest: The authors declare no conflict of interest.
Financing: The study was carried out with the financial support of Dr. Reddy's Laboratories.
Contribution of the authors to the preparation of the article
1. Contribution to the concept and plan of the study - D. V. Zaslavsky, Zakharova I. N., Shartanova N. V., A. N. Barinova;
2. Contribution to data collection – D. V. Zaslavsky, Zakharova I. N., Shartanova N. V., Berezhnaya I. V., Sidorovich O. I., A. N. Barinova; Zelyanina M.I
3. Contribution to data analysis and conclusions – D. V. Zaslavsky, A. N. Barinova, S. L. Plavinsky;
4. Contribution to the preparation of the manuscript - D. V. Zaslavsky, A. N. Barinova, S. L. Plavinsky.

 

About the authors

Denis V. Zaslavsky

Saint-Petersburg State Pediatric Medical University

Author for correspondence.
Email: venerology@gmail.com
ORCID iD: 0000-0001-5936-6232
SPIN-code: 5832-9510

MD, Dr. Sci. (Med.), Professor

Russian Federation, 2 Litovskay street, 194100 Saint-Peterburg

Anna N. Barinova

North-Western State Medical University named after I.I. Mechnikov; City Hospital № 26

Email: anna_n_barinova@mail.ru
ORCID iD: 0000-0002-8180-9340
SPIN-code: 2010-4354

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

Sviatoslav L. Plavinskij

North-Western State Medical University named after I.I. Mechnikov

Email: s.plavinskij@szgmu.ru
ORCID iD: 0000-0001-9159-6177
SPIN-code: 5660-4661

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Maria I. Zelyanina

The Pierre Wolkenstein French Dermatological Clinic

Email: m.zelianina@rambler.ru
ORCID iD: 0000-0002-0172-9763
SPIN-code: 3201-9685

MD

Russian Federation, Saint Petersburg

Irina N. Zakharova

Russian Medical Academy of Continuous Professional Education

Email: zakharova-rmapo@yandex.ru
ORCID iD: 0000-0003-4200-4598
SPIN-code: 4357-3897

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Irina V. Berezhnaya

Russian Medical Academy of Continuous Professional Education

Email: berezhnaya-irina26@yandex.ru
ORCID iD: 0000-0002-2847-6268

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Moscow

Natalia V. Shartanova

National Research Center - Institute of Immunology

Email: nshartanova@yandex.ru
ORCID iD: 0000-0002-1197-9002
SPIN-code: 6483-8901

MD, Dr. Sci. (Med.)

Russian Federation, Moscow

Olga I. Sidorovich

National Research Center - Institute of Immunology

Email: instimmun@yandex.ru
ORCID iD: 0000-0003-1000-0664
SPIN-code: 9757-8172

MD, Cand. Sci. (Med.), Senior Research Associate

Russian Federation, Moscow

References

Supplementary files