# A dermocosmetic regimen is able to mitigate skin sensitivity induced by a retinoid-based fixed combination treatment for acne: Results of a randomized clinical trial

Amir Khammari, Delphine Kerob, Ann' Laure Demessant, Margot Nioré, Brigitte Dréno

► To cite this version:

Amir Khammari, Delphine Kerob, Ann' Laure Demessant, Margot Nioré, Brigitte Dréno. A dermocosmetic regimen is able to mitigate skin sensitivity induced by a retinoid-based fixed combination treatment for acne: Results of a randomized clinical trial. Journal of Cosmetic Dermatology, 2023, Online ahead of print. 10.1111/jocr.16120. inserm-04350046

HAL Id: inserm-04350046

https://inserm.hal.science/inserm-04350046v1

Submitted on 5 Jun 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# A dermocosmetic regimen is able to mitigate skin sensitivity induced by a retinoid-based fixed combination treatment for acne: Results of a randomized clinical trial

Amir Khammari PhD<fnref n="1" />

Delphine Kerob MD<fnref n="2" /> ID

Ann' Laure Demessant Pharm D<fnref n="2" />

Margot Nioré MSc<fnref n="2" />

Brigitte Dréno MD, PhD<fnref n="3" />

### Correspondence

Brigitte Dréno, Nantes Université, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes, France.

Email: brigitte.dreno@atlanmed.fr

### Abstract

**Introduction:** Topical retinoids cause retinoid-induced skin discomfort (RISD) mainly during the first weeks of use leading to noncompliance and premature treatment discontinuation. A dermocosmetic (DC) may help to reduce treatment-related signs and symptoms and improve adherence.

**Objectives:** To assess the benefit of a DC regimen compared to a routine skin care regimen (RC) by reducing RISD signs and symptoms induced by a retinoid/benzoyl peroxide fixed-drug combination in subjects with acne.

**Materials and Methods:** Double-blind, randomized, comparative study in subjects ≥16 years with mild to moderate acne candidates to a topical adapalene/BPO fixed drug combination (A/BPO). Evaluations took place at Day 0, 7, 14, 28, and 84 and included erythema, desquamation, burning, itching and stinging and RISD (SD, a composite score of local treatment-related signs and symptoms and acne severity. Subjects used daily the DC or RC together with the fixed combination for 84 days.

**Results:** Eighty-eight subjects were included, the mean age was 21 years; 84% were females. At Day 0 the SD score was 0.8 in both groups. A statistically significant difference in terms of skin sensitivity with DC compared to RC (1.6 points, vs. 2.4 points *p* < 0.05) was observed at Day 14. Clinical sign and symptom scores were more reduced with DC than with RC at all time points. Acne severity improved in both groups.

**Conclusion:** DC significantly reduces A/BPO-related RISD compared to RC, especially during the first 14 days of treatment, without interfering with the clinical efficacy of the treatment, thus helping to maintain treatment adherence.

### KEYWORDS

acne, cleanser, cream, dermocosmetic regimen, retinoid-induced skin discomfort, skin sensitivity

This is an open access article under the terms of the [Creative Commons Attribution License](https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

© 2023 The Authors. *Journal of Cosmetic Dermatology* published by Wiley Periodicals LLC.

<footnote n="1">¹Department of Dermatology, Nantes University, CHU Nantes, CIC 1413, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, Nantes, France</footnote>

<footnote n="2">²La Roche-Posay Laboratoire Dermatologique, Levallois-Perret, France</footnote>

<footnote n="3">³Nantes University, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, Nantes, France</footnote>
# 1 | INTRODUCTION

Acne vulgaris is a chronic inflammatory skin disease with a high prevalence during adolescence, and a growing incidence in adults.<sup>1-4</sup> Its pathophysiology is multifactorial, with increased sebaceous glands and sebum production, hyperkeratinisation of the pilosebaceous infundibulum, skin microbiome disbalance, and innate immunity activation.<sup>5</sup>

Acne lesions are clinically characterized by retinal lesions, such as open or closed comedones, and inflammatory lesions, such as papules or pustules, which may ultimately evolve into either atrophic scars or marks (post-inflammatory erythema and post inflammatory hyperpigmentation).<sup>6</sup> Acne is mainly observed on the face, neck, chest, and upper back, where sebaceous follicles are predominant.<sup>7</sup>

Retinoids are the mainstay of acne treatments.⁸ However, they are associated with retinoid-induced skin discomfort (RISD), such as irritation, erythema and dryness, especially during the first 4 weeks of application.⁹⁻¹¹ Studies have been performed to mitigate this retinoid dermatitis and optimize treatment outcomes, such as intermittent regimens during the first weeks of treatment or association with moisturizers.¹²,¹³

The presently investigated dermocosmetic (DC) regimen consists of a cleanser and a cream formulation that has been developed to help to limit topical retinoid-induced RISD in subjects with acne. The DC cleanser (Effaclar® H Iso Biome cream wash, La Roche-Posay Laboratoire Dermatologique France) contains *Bixa Orellana* seed extract, niacinamide 2%, mannose, and APF (*Aqua Posae Filiformis*). The DC cream (Effaclar® H Iso Biome cream, La Roche-Posay Laboratoire Dermatologique France) contains *Bixa Orellana* seed extract, a plant extract that, in yet unpublished work, reduced sebum production, hyperkeratinisation, and that reduced lipase activity from *C. acnes*. Moreover, the cream contains niacinamide 2%, panthenol and the pre- and post-biotic APF.

Niacinamide is known to reduce the sebum outflow, while mannose improves the biomechanical properties of the skin.<sup>14,15</sup> APF reduces inflammation and helps to restore the natural skin barrier, while panthenol moisturizes the skin, thus further helping to restore the natural skin barrier.<sup>16</sup>

The aim of this study was to assess the benefit of a DC regimen compared to a standardized paraffine-based routine care (RC) regimen (skin cleansing gel and cream) by reducing RISD signs and symptoms induced by a retinoid/benzoyl peroxide fixed combination (Epiduo® 0.1%, Galderma International, France) in acne subjects.

# 2 | METHODOLOGY

This double-blind, prospective, comparative clinical study was conducted between September 2021 and May 2022 at one investigational site in France. The study received independent ethics committee approval and complied with Good Clinical Practices, the principles of the Declaration of Helsinki and legal local requirements for the conduct of this type of study. All participating subjects or

their caregivers, when appropriate, provided written informed consent prior to participation in this study.

Subjects were invited during their routine visit at the investigational site to participate in this investigation.

Suitable subjects of any skin phenotype had to be of at least 16 years of age and had to present with mild to moderate facial acne according to the GEA grading system (GEA grade II to III) and with at least 15 inflammatory lesions.<sup>17</sup> Subjects had to be a candidate to A/BPO to manage their acne and did not use any other treatment for their acne. Female subjects with premenstrual acne, being pregnant or breast-feeding, changing frequently their skin care or using masks or peelings and intolerant to one of the compounds were not suitable for this study.

Clinical evaluations took place at Day 0, 7, 14, 28, and Day 84, including erythema, desquamation, burning, itching and stinging, all assessed on a 4-point scale (none to important), RISD being a composite score of local treatment-related signs and symptoms and acne severity. Moreover, subjects assessed the cosmetic acceptability of both the DC and the RC regimen.

After inclusion, 88 subjects (2 blocks of 44 subjects each) were randomized in an equal manner or to the blinded DC or to the RC regimen using a randomization list generated by an independent statistician. Both the investigator and the subjects were not aware of the products allocated and were asked not to discuss about the products received during the study. Products were to be used for 84 days; the cleanser twice daily and the cream once daily in the morning. A/BPO was to be applied every evening. Subjects were asked to record their daily use. Compliance to treatment was verified during the study visits and noncompliance to treatment or missing data were noted in the case report form. No product weighing was performed at the end of the study.

The statistical analysis was performed using SAS® 9.4 software (SAS Institute, Cary, NC, USA). Quantitative variables were described by means, standard deviations, medians and interquartile ranges. Qualitative variables were described by the raw numbers of the different modalities and the corresponding percentages. To evaluate the primary endpoint, a Z-test for comparison of proportions was used for all comparisons of proportions. A Wilcoxon Signed Test was used for comparisons between two time points. For satisfaction and tolerance, a binary approach was used (favorable/unfavorable), prior to performing a proportion comparison test. The significance threshold was 5%; a significance level of *p* < 0.05 was considered as statistically significant.

# 3 | RESULTS

Overall, 88 subjects were included in this study (Figure 1); all completed the study. The mean age was 21.3±4.0 years; 84% of the subjects were females, the remaining 16% were males. Almost all subjects (89.8%) were of Phototype II or III. All subjects had mild or moderate acne with somewhat more subjects in the DC (31.8%) group than in the RC group (25.0%) having mild acne. The mean acne
<figure><img src="image_2.png" /><figcaption>FIGURE 1 Patient disposition.</figcaption></figure>

duration was 8.7±4.2 years, with the condition starting at a mean age of 12.6±2.8 years. In total, 81% of the subjects had a family history of acne, mostly among siblings (65% of patients) and mothers (48%). Family history among the fathers was reported for 28% of subjects.

At Day 0, all subjects had at least 10 noninflammatory and 15 inflammatory acne lesions at baseline. The mean noninflammatory lesion count was 22.6±7.0 lesions, that for inflammatory lesions 20.5±5.0 and that for total lesions 43.1±10.3, with no significant difference between either group. The overall mean RISD composite score was 0.8±0.9. Detailed demographic and main baseline data are given in Table 1.

According to the investigator, 47.7% of subjects in the DC group had mild and 2.3% moderate erythema, compared to 40.9% with mild erythema in the RC group; 2.3% of subjects in the RC group had mild desquamation. According to the subjects, 6.8% of the subjects in both groups reported mild itching. Mild tightening was reported by 15.9% and moderate tightening by 4.5% of the subjects in the DC; 20.5% of subjects in the RC group reported mild tightening. In the RC group, 4.5% of subjects reported a mild burning sensation.

After 7 days of care with the A/BPO-based fixed combination and the DC or RC regimens, the RISD score had increased more rapidly with the RC (2.6±0.3) than with the DC (2.2±0.3). After 14 days of care, it had decreased in both groups, with a significant mean difference (0.8 points, *p*=0.0049) in favor of the DC (1.6±0.3) compared to the RC (2.4±0.3). No significant difference was observed between either treatment group after this time point. However, the DC always continued to perform better than the RC (Figure 2).

At Day 0, 57.0% of the subjects reported at least one symptom (erythema, desquamation, itching, tightening, or burning sensations). This rate increased to 80.0% in the DC group and 89.0% in the RC after 7 days of treatment, remaining stable until the end of the study (DC: 81.0% vs. RC: 77.0%). No statistically significant difference between groups was observed at any post-Day 0 visit.

When detailing clinical signs and subject-reported symptoms, the percentage of subjects with erythema was comparable between the groups, with no significant difference at any time point. The percentage had increased from 50.0% in the DC and from 40.9% in the RC group at Day 0, to 69.8% and 61.4% respectively at Day 84. Conversely, the percentage of subjects with desquamation was always higher in the RC than in the DC group; differences were statistically significant at Day 14 (DC: 20.9% vs. RC: 43.2%, *p*<0.026) and Day 84 (DC: 20.9% vs. RC: 40.9%, *p*<0.044). A total of 6.8% of subjects in each group reported mild itching at Day 0. The percentage increased in both groups with 20.4% in the DC and 19.1% in the RC group reporting mild or moderate itching at Day 7, remaining stable at Day 14 and Day 28. At Day 84, 4.7% of subjects in the DC group reported mild itching compared to 6.8% and 2.3% of subjects reporting mild or moderate itching respectively in the RC group. Differences were statistically not significant. Tightening was reported by 20.4% (15.9% mild, 4.5% moderate) of subjects in the DC group and by 20.5% (mild only) in the RC group. These percentages increased after 7, 14, and 28 days, somewhat more in the RC than in the DC group at Day 7 and 14, and significantly (*p*<0.011) more (43.2%, mild: 36.4%, moderate: 6.8%) than in the DC group (18.1%, mild: 13.6%, moderate: 4.5%). After 84 days, percentages had returned to Day 0 values, with no statistically significant difference. The burning sensation increased in both groups after the first 7 days of treatment (DC: 0% vs. 31.8%; RC: 4.5% vs. 27.3%) remaining stable at Day 14 and Day 28 and decreasing after 84 days of treatment (DC: 14.0% vs. RC: 13.6%). Differences were statistically not significant. Figure 3 shows the evolution over time of the percentage of subjects with clinical symptoms in both treatment groups.

The GEA score in both groups decreased over time from 2.7 and 2.8–1.4 and 1.5, for the DC and RC groups respectively (Figure 4).

The total number of non-inflammatory lesions decreased over time, from 23.5 lesions on average at Day 0 to 10.5 lesions at Day 84 in the DC, and from 21.7 to 10.8 lesions in the RC group. The number of inflammatory lesions also decreased over time, from 20.2 lesions on average at Day 0 to 5.2 lesions at Day 84 in the DC, and from 20.8 to 6.1 lesions in the RC group. The total number of acne lesions decreased over time, from 43.7 lesions on average at Day 0 to 15.7 lesions at Day 84 in the DC, and from 42.5 to 17.0 lesions in the RC group. At any time point, between-group differences were statistically nonsignificant.

The cosmetic acceptability at the end of the study was somewhat better for the DC than for the RC regimen, especially for the DC cleanser, for which subjects considered that it had a pleasant texture (DC: 72.1% vs RC: 45.5%, *p*=0.018), that it did not dry the skin (DC: 20.9% vs. RC: 9.1%, *p*=0.016), that it foamed well (DC: 48.8% vs. RC: 20.5%, *p*=0.004) and that it helped to reduce discomfort (DC: 16.3% vs. RC: 4.5%, *p*=0.001). Moreover, compared to the RC, the DC provided a feeling of well-being (DC: 23.3% vs RC: 4.5%, *p*=0.004), that it respected the skin (DC: 25.6% vs. RC: 4.5%, *p*=0.003), that it left the skin comfortable
<table><caption>TABLE 1 Demographic and main baseline data.</caption><thead><tr><th></th><th>Dermocosmetic group (N=44)</th><th>Routine care group (N=44)</th><th>Global study population (N=88)</th></tr></thead><tbody><tr><td>Age</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>21.18±3.92</td><td>21.39±4.10</td><td>21.28±3.99</td></tr><tr><td>Min; Max</td><td>16.00; 33.00</td><td>18.00; 44.00</td><td>16.00; 44.00</td></tr><tr><td>Median</td><td>20.00</td><td>21.00</td><td>20.00</td></tr><tr><td>Q1; Q3</td><td>19.00; 22.00</td><td>19.00; 22.00</td><td>19.00; 22.00</td></tr><tr><td>Duration of acne (year)</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>8.98±4.13</td><td>8.41±4.72</td><td>8.69±4.42</td></tr><tr><td>Min; Max</td><td>3.00; 21.00</td><td>2.00; 31.00</td><td>2.00; 31.00</td></tr><tr><td>Median</td><td>8.00</td><td>7.00</td><td>8.00</td></tr><tr><td>Q1; Q3</td><td>7.00; 11.00</td><td>6.00; 10.50</td><td>6.00; 11.00</td></tr><tr><td>Age at onset of acne</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>12.20±2.25</td><td>12.98±2.25</td><td>12.59±2.27</td></tr><tr><td>Min; Max</td><td>8.00; 19.00</td><td>9.00; 21.00</td><td>8.00; 21.00</td></tr><tr><td>Median</td><td>12.00</td><td>13.00</td><td>12.00</td></tr><tr><td>Q1; Q3</td><td>10.50; 13.50</td><td>12.00; 14.00</td><td>11.00; 14.00</td></tr><tr><td>GEA score</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>2.68±0.47</td><td>2.75±0.44</td><td>2.72±0.45</td></tr><tr><td>Min; Max</td><td>2.00; 3.00</td><td>2.00; 3.00</td><td>2.00; 3.00</td></tr><tr><td>Median</td><td>3.00</td><td>3.00</td><td>3.00</td></tr><tr><td>Q1; Q3</td><td>2.00; 3.00</td><td>2.50; 3.00</td><td>2.00; 3.00</td></tr><tr><td>Total noninflammatory lesion count</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>23.45±6.97</td><td>21.68±6.96</td><td>22.57±6.99</td></tr><tr><td>Min; Max</td><td>14.00; 42.00</td><td>10.00; 39.00</td><td>10.00; 42.00</td></tr><tr><td>Median</td><td>21.00</td><td>20.00</td><td>20.50</td></tr><tr><td>Q1; Q3</td><td>18.50; 28.00</td><td>17.00; 25.50</td><td>18.00; 27.00</td></tr><tr><td>Total inflammatory lesion count</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>20.23±4.15</td><td>20.82±5.79</td><td>20.52±5.01</td></tr><tr><td>Min; Max</td><td>15.00; 31.00</td><td>15.00; 44.00</td><td>15.00; 44.00</td></tr><tr><td>Median</td><td>19.50</td><td>20.00</td><td>20.00</td></tr><tr><td>Q1; Q3</td><td>17.00; 21.50</td><td>17.50; 21.00</td><td>17.00; 21.00</td></tr><tr><td>Total lesion count</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>43.68±9.37</td><td>42.50±11.23</td><td>43.09±10.30</td></tr><tr><td>Min; Max</td><td>31.00; 68.00</td><td>26.00; 80.00</td><td>26.00; 80.00</td></tr><tr><td>Median</td><td>41.00</td><td>38.50</td><td>40.00</td></tr><tr><td>Q1; Q3</td><td>36.00; 50.00</td><td>36.50; 47.00</td><td>36.00; 49.00</td></tr><tr><td>Retinoid-induced skin discomfort composite score</td><td></td><td></td><td></td></tr><tr><td>Mean±SD</td><td>0.84 (+/-0.96)</td><td>0.75 (+/-0.78)</td><td>0.80 (+/-0.87)</td></tr><tr><td>Min; Max</td><td>0.00; 4.00</td><td>0.00; 3.00</td><td>0.00; 4.00</td></tr><tr><td>Median</td><td>1.00</td><td>1.00</td><td>1.00</td></tr><tr><td>Q1; Q3</td><td>0.00; 1.00</td><td>0.00; 1.00</td><td>0.00; 1.00</td></tr></tbody></table>

(DC: 23.3% vs. RC: 6.8%, *p* = 0.004), and that it was not irritating (DC: 30.2% vs. RC: 6.8%, *p* < 0.001). Significantly, (*p* = 0.014) more subjects stated that they would replace their usual cleanser with the DC (18.6%) rather than with the RC cleanser (13.6%), and significantly (*p* = 0.024) more subjects would recommend the

DC (25.6%) than the RC cleanser (20.5%). Regarding the moisturizing cream, more subjects agreed that the DC compared to the RC cream (72% vs. 41%, *p* < 0.019) did not leave an oily/sticky layer and that it would be an ideal make-up base (DC: 35% vs. RC: 16%, *p* < 0.021).
<figure><img src="image_3.png" /><figcaption>FIGURE 2 Evolution of the mean retinoid-induced skin discomfort composite score over time. *p=0.049.</figcaption></figure>

<figure><img src="image_4.png" /><figcaption>FIGURE 3 Evolution over time of the percentage of subjects with clinical symptoms and symptoms in both treatment groups.</figcaption></figure>

4 | DISCUSSION

Topical retinoids are known to cause erythema, irritation, and desquamation, especially during the first 4 weeks of their administration.¹⁸,¹⁹ These signs and symptoms are associated with RISD, and may lead to a decrease in adherence and, ultimately, in treatment efficacy. Thus, preventing this RISD from the start of any retinoid-based acne treatment may help to reduce RISD, increase compliance

and treatment outcome. This was already pointed out in 2010.²⁰ The authors reported that DC increase patient satisfaction with therapy and thus compliance, which is one of the reasons why current treatment guidelines recommend the adjuvant use of emollients and moisturizers.²¹,²²

Results from the present study show that a specific DC regimen, including a low pH cleanser and a noncomedogenic cream developed to protect the skin physical barrier and microbial barrier in patients
<figure><img src="image_5.png" /><figcaption>FIGURE 4 Evolution of the GEA score overtime in both treatment groups.</figcaption></figure>

treated with retinoid-based acne treatment, is able to improve clinical signs and symptoms induced by an adapalene/benzoyl peroxide fixed combination.

The optimal pH of skin is between 4.7 and 5.75. Therefore, it is important for cleansers to have a pH within that range.²³ Aggressive skin care regimens and inappropriate cosmetics such as too greasy or oily soaps with an alkaline pH can cause acne flares by changing the skin barrier and microbiota, resulting in increased inflammation.²⁴

Acne can be worsened by aggressive cleansing or by using a cleanser with an unsuitable pH. Therefore, a DC cleanser with a pH close to that of normal skin may be less irritating and increase patient adherence.²⁵ Moreover, the use of noncomedogenic, non-acnogenic moisturizer is important to counteract the drying effect of some acne medications especially retinoids.²⁶

The tested DC regimen was significantly (p = 0.0049) more beneficial in reducing RISD after 14 days of use with a sustained benefit until the end of the study. Moreover, the DC regimen was more beneficial in reducing clinical signs and symptoms than the RC regimen.

Subjects significantly (all *p* < 0.05) preferred the DC over the RC regimen for its pleasant texture, capacity to limit dryness, irritation and RISD, well-being, skin respect and comfort. Significantly more subjects stated that they would replace their usual cleanser with the DC rather than with the RC cleanser, that the DC cream was an ideal make-up basis and that they would more easily recommend the DC than the RC regimen.

In conclusion, the present study shows that the tested DC significantly reduces A/BPO fixed combination-induced RISD in subjects with mild to moderate acne after 14 days of adjuvant use.

## AUTHOR CONTRIBUTIONS

Amir Khammari, Brigitte Dréno, Delphine Kerob, Ann' Laure Demessant and Margot Nioré developed the protocol. Amir Khammari and Brigitte Dréno conducted the study. All authors participated in the production and review of the manuscript.

## ACKNOWLEDGMENTS

The authors acknowledge the writing support of Karl Patrick Göritz, SMWS, France.

## FUNDING INFORMATION

The study was financed by La Roche-Posay Laboratoire Dermatologique.

## CONFLICT OF INTEREST STATEMENT

Delphine Kerob, Ann' Laure Demessant and Margot Nioré are employees of La Roche-Posay Laboratoire Dermatologique.

## DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

## ETHICS STATEMENT

The study received independent ethics committee approval (IDRCB number: 2021-A00567-34, IEC Poitiers, 05 May 2021).

## ORCID

Delphine Kerob https://orcid.org/0000-0003-2816-4261

## REFERENCES

1. Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. *F1000Res*. 2018;7:7.

2. Dreno B. What is new in the pathophysiology of acne, an overview. *J Eur Acad Dermatol Venereol*. 2017;31(Suppl 5):8-12.

3. Bagatin E, Freitas THP, Rivitti-Machado MC, et al. Adult female acne: a guide to clinical practice. *Ann Bras Dermatol*. 2019;94(1):62-75.

4. Addor FA, Schalka S. Acne in adult women: epidemiological, diagnostic and therapeutic aspects. *Ann Bras Dermatol*. 2010;85(6):789-795.

5. Dreno B, Martin R, Moyal D, Henley JB, Khammari A, Seité S. Skin microbiome and acne vulgaris: staphylococcus, a new actor in acne. *Exp Dermatol*. 2017;26(9):798-803.

6. Degitz K, Placzek M, Borelli C, Plewig G. Pathophysiology of acne. *J Dtsch Dermatol Ges*. 2007;5(4):316-323.

7. Kurokawa I, Layton AM, Ogawa R. Updated treatment for acne: targeted therapy based on pathogenesis. *Dermatol Ther*. 2021;11(4):1129-1139.

8. Leyden J, Stein-Gold L, Weiss J. Why topical Retinoids are mainstay of therapy for acne. *Dermatol Ther*. 2017;7(3):293-304.

9. Phillips TJ. An update on the safety and efficacy of topical retinoids. *Cutis*. 2005;75(2 Suppl):14-22.

10. Tirado-Sánchez A, Espíndola YS, Ponce-Olivera RM, Bonifaz A. Efficacy and safety of adapalene gel 0.1% and 0.3% and tretinoin gel 0.05% for acne vulgaris: results of a single-center, randomized, double-blinded, placebo-controlled clinical trial on Mexican patients (skin type III-IV). *J Cosm Dermatol*. 2013;12(2):103-107.

11. Thiboutot D, Arsonnaud S, Soto P. Efficacy and tolerability of adapalene 0.3% gel compared to tazarotene 0.1% gel in the treatment of acne vulgaris. *J Drugs Dermatol*. 2008;7(6 Suppl):s3-s10.

12. Tan J, Bissonnette R, Gratton D, Kerrouche N, Canosa JM. The safety and efficacy of four different fixed combination regimens of adapalene 0.1%/benzoyl peroxide 2.5% gel for the treatment of acne vulgaris: results from a randomised controlled study. *Eur J Dermatol*. 2018;28(4):502-508.

13. Hayashi N, Kawashima M. Study of the usefulness of moisturizers on adherence of acne patients treated with adapalene. *J Dermatol*. 2014;41(7):592-597.
14. Draelos ZD, Matsubara A, Smiles K. The effect of 2% niacinamide on facial sebum production. *J Cosmet Laser Ther*. 2006;8(2):96-101.

15. Meunier M, Chapuis E, Lapierre L, et al. Mannose-6-phosphate complex and improvement in biomechanical properties of the skin. *J Cosm Dermatol*. 2021;20(6):1598-1610.

16. Camargo FB Jr, Gaspar LR, Maia Campos PM. Skin moisturizing effects of panthenol-based formulations. *J Cosmet Sci*. 2011;62(4):361-370.

17. Dreno B, Poli F, Pawin H, et al. Development and evaluation of a global acne severity scale (GEA scale) suitable for France and Europe. *J Eur Acad Dermatol Venereol*. 2011;25(1):43-48.

18. Culp L, Moradi Tuchayi S, Alinia H, Feldman SR. Tolerability of topical Retinoids: are there clinically meaningful differences among topical Retinoids? *J Cutan Med Surg*. 2015;19(6):530-538.

19. Yang Z, Zhang Y, Lazic Mosler E, et al. Topical benzoyl peroxide for acne. *Cochrane Database Syst Rev*. 2020;3(3): Cd011154.

20. Dreno B, Thiboutot D, Gollnick H, et al. Large-scale worldwide observational study of adherence with acne therapy. *Int J Dermatol*. 2010;49(4):448-456.

21. Nast A, Dreno B, Bettoli V, et al. European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version. *J Eur Acad Dermatol Venereol*. 2016;30(8):1261-1268.

22. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. *J Am Acad Dermatol*. 2016;74(5):945-973.

23. Blaak J, Staib P. The relation of pH and skin cleansing. *Curr Probl Dermatol*. 2018;54:132-142.

24. Dreno B, Bettoli V, Araviiskaia E, Sanchez Viera M, Bouloc A. The influence of exposome on acne. *J Eur Acad Dermatol Venereol*. 2018 May;32(5):812-819.

25. Araviiskaia E, Lopez Estebaranz JL, Pincelli C. Dermocosmetics: beneficial adjuncts in the treatment of acne vulgaris. *J Dermatol Treat*. 2021;32(1):3-10.

26. Araviiskaia E, Dréno B. The role of topical dermocosmetics in acne vulgaris. *J Eur Acad Dermatol Venereol*. 2016;30(6):926-935.

**How to cite this article:** Khammari A, Kerob D, Demessant AL, Nioré M, Dréno B. A dermocosmetic regimen is able to mitigate skin sensitivity induced by a retinoid-based fixed combination treatment for acne: Results of a randomized clinical trial. *J Cosmet Dermatol*. 2024;23:1313-1319.
doi:10.1111/jocd.16120