Efficacy of a multitargeted, salicylic acid‐based dermocosmetic cream compared to benzoyl peroxide 5% in Acne vulgaris: Results from a randomized study

Acne vulgaris (acne) is characterized by both inflammatory and non‐inflammatory lesions. Benzoyl peroxide (BPO) 5% is approved to treat acne but may cause skin irritation and/or contact allergy.


| INTRODUC TI ON
Acne vulgaris (acne) is a chronic inflammatory skin condition involving the pilosebaceous gland. 1 It initially forms micro-comedones, which evolve into non-inflammatory or inflammatory lesions that can ultimately evolve into acne marks, such as scars or even post-inflammatory hyperpigmentation in darker skin phototypes. 2 In severe forms, refractory cysts and nodules may be observed.Acne mainly appears in sebaceous follicle-rich areas of the body, such as the face, neck, and trunk. 3[6] Four factors are considered in the pathophysiology of acne, including abnormal proliferation and differentiation of keratinocytes in the hair follicle, increased sebum production and modified composition, microbial dysbiosis, and host inflammatory response. 1The skin commensal Cutibacterium acnes (C.8][9] Recently, the loss of balance between the different C. acnes phylotypes, with the C. acnes phylotype IA1 being predominant in acne, combined with a dysbiosis of the skin microbiome, was proposed as participating in the pathology of acne.This loss of strain diversity may disproportionately activate the innate immune system, causing inflammation in the skin. 7rrent acne treatments include different topical and systemic treatments.Benzoyl peroxide (BPO) is approved at different concentrations and recommended in monotherapy to manage mild-to-moderate acne. 10In addition to its antibacterial properties, BPO has mild anti-inflammatory and comedolytic activities. 11,12However, treatment with BPO may also be accompanied by local side effects, such as irritation and erythema. 13aditionally, pharmacological treatments are indicated to treat acne.Today, dermocosmetics are recognized more and more as playing a role in the management of acne, either to manage milder forms as a standalone or as adjuncts to pharmacological treatments for more severe forms. 14is clinical study assessed the benefit in acne of a dermocosmetic (DC-Eff, Effaclar® Duo+, La Roche-Posay Laboratoire Dermatologique, France) that contains salicylic acid, lipohydroxy acid (LHA), niacinamide, 2-oleamido-1,3-octadecanediol, piroctone olamine, zinc gluconate, the pre-and probiotic Aqua posae filiformis, and La Roche-Posay thermal water.6][17][18][19][20] Aqua posae filiformis is able to restore the natural skin barrier and 2-oleamido-1,3-octadecanediol is a patented ceramide that reduces red or brownish blemishes.
A recent study showed that in subjects with mild-to-moderate acne, DC-Eff was more beneficial in combination with BPO 5% than in monotherapy. 21Subjects who agreed to participate in the study were asked to stop all current acne care and to use a provided mild cleanser and moisturizer for the 2 weeks preceding inclusion.

| MATERIAL S AND ME THODS
Subjects were randomized at baseline to receive either DC-Eff or BPO 5% (Cutacnyl® AC, Galderma International) applied twice daily for 56 days.Subjects were also asked to continue the daily use of the provided cleanser once or twice a day and to apply the moisturizer or their current make-up products (foundation and powder) in the morning, 10 min after the application of the test products.
The IGA (investigator global assessment on a scale from 0 = none to 4 = severe), GEA scoring, lesions counts (IL, NIL, and TL total lesions), and the evaluation of redness (on a scale from 0 = no redness to 9 = strong redness) were performed at baseline and after 28 (D28) and 56 (D56) days.Subjects rated the perceived efficacy and product qualities at D28, and D56.Local tolerance was reported for the entire course of the study.
The statistical analysis was performed using R version 4.1.3.All criteria were submitted to descriptive statistics in terms of raw data and change from baseline per time point using means, standard deviations, median, number of subjects, minimal value, maximal value, and first and third quantiles.For categorical variables, the frequency and percentage of each category were provided.Comparisons versus baseline and between the two treatment groups were performed using the Wilcoxon rank-sum test or a linear mixed model.
The significance threshold was 5%, which was considered statistically significant.A Benjamini-Hochberg adjustment of p-values was used for multiple comparisons on primary criteria.

| Demographic and baseline data
Overall, 150 subjects were included in this study; of these, 50.7% were female.Both groups were comparable regarding demographic and disease severity, except for subjects in the BPO group who presented with somewhat more NIL at baseline (between-group difference not significant).Detailed baseline data are provided in Table 1.
Of the 150 subjects included, 2 subjects, one in each group, prematurely stopped the study for personal reasons.

| Clinical efficacy
The responder analyses of the IGA and GEA scores showed that 62.2% and 47.3%, respectively, in the DC-Eff, compared with 50.0% and 36.5% respectively in the BPO, had improved by at least one point at D56.
No subject had an increased IGA and one subject had a worsened GEA score with DC-Eff.Conversely, the IGA score worsened for one subject and the GEA score for 2 subjects in the BPO group (see Figures 1 and 2). in Figures 3 and 4, respectively.The TL count decreased for DC-Eff by 34.0% at D28 and by 54.7% at D56. Changes from baseline in the BPO group were −33.8% at D28 and −54.2% at D56 (Figure 5).Differences from baseline were statistically significant (p < 0.001) in both treatment groups at D28 and D56.There was no difference between either group.

| Redness
Redness significantly (p < 0.001) improved over time in both groups with a non-statistically significant between-group difference.The detailed evolution of the different severity scores is given in Figure 6.
TA B L E 1 Subject demographic and baseline data.

| Product perception
Subjects in both groups self-reported a reduction of the perceived acne severity and declared a feeling of healthier skin, clearer and cleaner skin, a less oily look, and less visible pores.At D56, subjects considered that DC-Eff improved the smoothness of their skin (96.0%) and appreciated the ease of product application (89.2%).

F I G U R E 3 Evolution of inflammatory lesion count between baseline and D56 (mean ± CI95
).The decrease in inflammatory lesions from baseline was statistically significant (p < 0.001) for both groups at D28 and D56.

| DISCUSS ION
Results from this randomized study show that in subjects with mildto-moderate acne, a multitargeted dermocosmetic, DC-Eff, used twice daily for 56 days, improves acne according to the IGA and GEA assessments, and reduces acne lesion counts (IL, NIL, TL).Moreover, DC-Eff significantly improves the clinical signs and symptoms of acne (p < 0.001) as early as 28 days.
Topical BPO has been approved for the treatment of acne for over 60 years.However, its use has historically been limited due to tolerability, photosensitivity, oxidation, and, uncommonly, contact allergy issues, and even though its local tolerance has been improved thanks to the development of new formulations, a risk of irritation and skin dryness with BPO may persist. 23,24Moreover, as BPO is a bleaching agent, users have frequently been reticent to use this product when wearing colored clothing. 25Over the last years, DCs have become an important alternative to pharmacologically active treatments to treat milder forms of acne with improved formulations that increase their benefit, accompanied by good tolerability.

F I G U R E 4 Evolution of non-inflammatory lesion count between baseline and D56 (mean ± CI95
).The decrease in non-inflammatory lesions from baseline was statistically significant (p < 0.001) for both groups at D28 and D56.
F I G U R E 5 Evolution of total lesion count between baseline and D56 (mean ± CI95).The decrease in total lesions from baseline was statistically significant (p < 0.001) for both groups at D28 and D56.
F I G U R E 6 Evolution of clinical redness between baseline and D56 (mean ± CI95).The decrease in redness scores from baseline was statistically significant (p < 0.001) for both groups at D28 and D56.
This randomized study was conducted between February and May 2019 at one investigational site in Ukraine.The study received ethics committee approval (#007, Vidnovlennya, Zhytomir, February 21, 2019) and respected the principles of the Declaration of Helsinki as well as Good Clinical Practices.All subjects who participated in this study provided written informed consent prior to inclusion.Suitable subjects were Caucasian (phototypes I-III), aged between 18 and 40 years, who presented oily skin and mild-to-moderate acne according to the GEA scale (Global Evaluation of Acne scale ranging from 0 = none to 5 = very severe).In addition, subjects had to have at least 10 inflammatory lesions (IL) and 10 non-inflammatory lesions (NIL) on the face.

1
Number of responders: change of IGA score from baseline at D28 and D56.

F I G U R E 2
Number of responders: change of GEA score from baseline at D28 and D56.

DC-Eff group N = 75 BPO-group N = 75
DC-Eff was tolerated better than BPO, with fewer product-related adverse reactions.A total of 6 subjects reported 8 signs of discomfort during the study, with DC-Eff being mainly very mild to mild in intensity and transient.In the BPO group, 8 volunteers reported 13 signs; most of them were very mild to moderate in intensity.