Dermocosmetics as an integral part of isotretinoin therapy in acne patients: results of an observational study

Introduction

Acne is one of the most often encountered inflammatory skin diseases, and a global perspective on its epidemiology suggests that the acne prevalence is still growing [1]. Although acne may occur at any age, the peak incidence is in postpubescent teens. The pathogenesis is complex and encompasses synergic interplay of different factors [2]. A range of cellular pathways and hormones may influence sebocyte activity, keratinization abnormalities, and perturbation in skin microbiota, ultimately leading to pilosebaceous follicle inflammation [3]. This intricacy poses therapeutic challenges. The management of acne has changed significantly over the years, and undoubtedly, the breaking point was the introduction of isotretinoin, a synthetic retinoid derived from retinol [4]. The effectiveness of this drug has been confirmed in many clinical studies and is well documented in the literature. Nowadays, isotretinoin is considered the so-called gold standard for moderate and severe acne that should be promptly introduced to prevent sequelae like postinflammatory hyperpigmentation, acne-induced erythema, or scarring (both, hypertrophic and atrophic) [5]. However, one of the most challenging aspects of this management is side effect such as skin dryness that occurs almost in all patients during treatment [6, 7]. It seems that a treatment regimen with dedicated topical dermocosmetics may help to increase acceptability and adherence to isotretinoin therapy [8].

Objective

In this study, we present the observational study aimed to show the impact of the dermocosmetics, Effaclar H Iso-Biome cream and Effaclar H Iso-Biome washing cream used along with isotretinoin in the group of patients with moderate to severe acne vulgaris.

Material and methods

This was a 12-week observational study to evaluate the efficacy and safety of Effaclar H Iso-Biome cream and Effaclar H Iso-Biome washing cream preparations as an adjunct to isotretinoin therapy in moderate to severe acne vulgaris. All participants voluntarily signed and dated the informed consent. Patients were eligible to be included in this study only if all of the following requirements applied: diagnosis of moderate to very severe acne vulgaris according to the criteria of the Global Acne Severity Scale (GEA), treatment with oral isotretinoin and age above 14 years. Female participants could not be pregnant or breastfeeding. All subjects should follow a therapeutic scheme each morning and evening (twice daily). Effaclar H Iso-Biome washing cream should be used on wet skin, then rinsed with water and gently pat dried with a towel. Subsequently, patients should apply Effaclar H Iso-Biome cream. A thin layer of the cream should be administered to cover the whole skin surface. The entire study period consisted of the screening visit and evaluation visits. At each visit, a qualified dermatologist graded acne severity according to the GEA score [9]. A questionnaire containing questions referring to demographic data (gender, age), skin phototype, use of contraception, severity of sebum secretion, assessment of skin sensitivity and acne sequelae (hyperpigmentation, erythema, and scarring) was completed at all scheduled time points. The safety review regarding adverse events and local tolerability was performed at the evaluation visit. All patients were queried about their quality of life index and subjective feelings (pruritus, pain, stinging, or tingling) at both visits and satisfaction with the treatment regimen survey at the evaluation visit.

Patient characteristics

We identified 109 patients who started combined treatment of isotretinoin and Effaclar H Iso-Biome preparations. The population selected for this study reflects a standard population for moderate to severe acne vulgaris. Participants at the age of 18 to 21 years were the most prevalent. More than half of the patients were women with phototype II (according to the Fitzpatrick scale). In 30.3% of all cases, patients reported the occurrence of acne 3–5 years before the screening visit. There was a predominance of women using combined estrogen-progestin oral contraceptives. Before the introduction of the treatment regimen, acne severity was evaluated as GEA 5 in 10.1%, GEA 4 in 45.9% and GEA 3–2 in 44% of participants, The papulopustular subtype of acne was observed in almost 60% of the studied group. Lesions were mainly located on both cheeks (U-zone) – 85.3%. At screening visits, acne scars, hyperpigmentation and erythema have been documented in 63.3%, 48.6%, and 48.6%, respectively. Patient characteristics of the total cohort are summarized in table 1.

Statistical analysis

To evaluate the results of this study, a non-parametric test for two dependent samples (Wilcoxon signed-rank test) was performed. P-values less than 0.05 were considered significant.

Results

Following 12 weeks of isotretinoin with Effaclar H Iso-Biome washing cream and Effaclar H Iso-Biome cream application, acne severity was assessed as GEA 2 or less in 71.6% of patients. Improvement of 2 or more grades on the GEA score was noted in 48.6% (p < 0.05) (fig. 1). The sebum-suppressive effect was observed in all patients and did not increase during topical treatment (fig. 2). None of the participants reported sebum secretion above grade 5 (measured by the NRS score, where 0 means no sebum secretion and 10 means very severe sebum secretion). Postinflammatory hyperpigmentation was found in 35.8% of acne patients compared to 48.6% before treatment. At the evaluation visit, there was a significant reduction in erythema (fig. 3): a statistically significant change in redness was achieved in 61.6% of patients (p < 0.05). It is worth noting that after the treatment course, 53.2% of participants presented no scaling, and in 57.4%, a marked improvement was observed (fig. 3). There was also a trend towards reduction of dryness (fig. 3). Improvement was reported in 58.9% of the patients, with a complete resolution of acne lesions in 44%. This translates to a decrease in patient’s subjective sensations like pruritus, tingling, and stinging (fig. 4).

Life of quality index

The long-lasting psychosocial effects of acne were widely described in the literature. In our study, we assessed several aspects of acne’s impact on patients’ lives: aggressive behaviours, social life, avoidance of public places (like changing rooms), feelings related to the presence of skin lesions, and relationships with others. Quality of life was improved at week 12 in all aspects. Upon receipt of isotretinoin with Effaclar H Iso-Biome preparations, social isolation decreased in 69.7% of surveyed patients, whereas more than 50% of patients started to utilize public zones. The tendency to experience emotions of anger improved markedly in 77.1% of subjects. Additionally, at the evaluation visit, 79.8% of respondents showed a sustained improvement in anxiety and depression feelings.

Discussion

Effaclar H Iso-Biome: active ingredients

The active ingredients of prescribed dermocosmetics play a crucial role in anti-acne strategies. The formula of Effaclar H Iso-Biome preparations contain anti-inflammatory, sebum-controlling, antimicrobial, and skin barrier-protecting agents [10].
One of the most potent antimicrobial and antioxidant active substances is the extract of Bixa orellana seeds. Bixa orellana is a plant widely found in South America [11]. A carotenoid pigment called anatto comes from Bixa orellana seeds and its main active ingredients are bixin and norbixin [11]. Across the literature, many studies already proved its strong antibacterial and antifungal properties [12]. Franklin et al. investigated whether a gel containing the aqueous extract of Bixa orellana can effectively heal rat skin [13]. After 14 days, a decrease of the wound area was observed in 94.97% of studied rats, while in the group receiving topical fibrinase in only 56.58%. The authors concluded that urucum aqueous extract is more efficient than fibrinase [13]. Moreover, Bixa orellana may inhibit lipase production of C. acnes and thus reduce the release of free fatty acids from sebum triglycerides [14]. It is well known that higher concentrations of free fatty acids cause keratinization disorders and exacerbate inflammation, which explains why inhibiting lipase is beneficial in treating acne.
Another unique ingredient is Aqua posae filiformis [15]. Dysbiosis of skin microbiota contributes to the pathogenesis of acne, especially in promoting phylotype IA1 of C. acnes [16]. Vitreoscilla filiformis is a topical probiotic bacterium cultured by a fermentation process, which can beneficially influence the skin microbiota and help maintain homeostasis [17]. Vitreoscilla filiformis is cultivated in La Roche-Posay thermal spring water to obtain unique properties. The selenium-rich environment improved bacterial growth and acted as a catalyzer for bacterial enzymes. The lysate of Vitreoscilla filiformis is produced with the help of high temperature [17]. Topical use of lysate of Vitreoscilla filiformis stimulates antimicrobial peptides and endogenous antioxidant defenses.
Effaclar H Iso-Biome’s formula also contains niacinamide and zinc, which are well-tolerated and safe ingredients that elicit strong anti-inflammatory and sebostatic effects [18]. Several clinical trials compared niacinamide with clindamycin gel. All studies demonstrated similar or even superior effectiveness of a niacinamide preparation in acne patients [19, 20].
Last but not least, humectants such as glycerin and panthenol decrease transepidermal water loss and play an important role in delivering other active ingredients through the epidermis [21, 22].
Systemic isotretinoin has become the first choice of treatment for severe acne vulgaris since its introduction. The international acne treatment guidelines recommend fast initiation of isotretinoin to prevent scarring [5]. After almost three decades, isotretinoin showed a relatively good safety profile. However, one of the main concerns causing a decrease in adherence is dose-dependent cutaneous side effects, like excessive skin dryness [23]. From the molecular point of view, isotretinoin mediates sebocyte apoptosis, which further leads to the involution of sebaceous glands. Moreover, clinical data showed that isotretinoin impacts the stratum corneum thickness and hydration level, causing skin barrier disruption [24]. Therefore, active ingredients found in dermocosmetics may help reverse those side effects and maintain the skin homeostasis [25].
In recent years, the supporting role of dermocosmetics in acne treatment has been highlighted. However, there are only few clinical trials assessing their efficacy across the literature. In a double-blind, randomized, placebo-controlled study, Herane et al. compared the effectiveness of hydrating gel-cream containing hyaluronic acid, biosaccharide gum-2 and 7% glycerin with placebo in the group of patients with acne, treated with oral isotretinoin [26]. The results of this study showed a significant increase in the hydration level of the skin in the active group, 41.88 before vs. 47.44 after treatment; p < 0.01. Moreover, transepidermal water loss tended to grow in the placebo group, with no significant changes in the active group. Another trial conducted by Tahiliani et al. investigated the effectiveness and tolerability of a moisturizer as an adjuvant to isotretinoin in the group of 200 patients with acne in the 4-week treatment period [27]. In the treated group there was no severe redness, scaling or xerosis.
Our previously conducted study already proved that Effaclar H Iso-Biome preparations are safe and effective products as adjunctive treatment to topical or systemic therapy of mild to very severe acne vulgaris [28]. In the current research we focused on the effectiveness in alleviation of the isotretinoin treatment sequels and tolerability of Effaclar H Iso-Biome cream and Effaclar H Iso-Biome washing cream in acne patients. To obtain the most independent results we used investigator’s clinical assessment along with subject’s assessment questionnaires. Regular use of those preparations improved skin sensitivity measured by intensity of erythema, dryness, and scaling. 97.3% of all patients rated tolerance as high or excellent. According to cosmetic proprieties, more than 90% of patients described the formula as not greasy or sticky, gentle for the skin, and easy to apply. Subjects also appreciated the feeling of clean and moisturized skin after using Effaclar H Iso-Biome preparations. There was no induction of excessive sebum production. Importantly, no incidence of product-related adverse events was reported.
Limitations: This study also has some limitations. One of them is restricted time of observation. Secondly, the study cohort mainly consisted of patients with skin phototypes II and I (according to the Fitzpatrick scale).

Conclusions

Effaclar H Iso-Biome cream and washing cream were safe and effective products as an adjunct to isotretinoin. In this 12-week observational period, majority of patients benefitted from the topical, twice-daily application regimen. Furthermore, Effaclar H Iso-Biome preparations significantly decreased cutaneous side effects of isotretinoin, such as dryness, erythema, and scaling, which led to improvement in patients’ quality of life.

Acknowledgments

We would like to thank all doctors and patients for participation in the study and their commitment.

Funding

This work was supported by a grant from La Roche-Posay.

Ethical approval

Not applicable.

Conflict of interest

Dominika Kwiatkowska has been a subinvestigator in clinical trials sponsored by Galderma, AbbVie, leo Pharma, Argenx, Syneos Helth, Celltrion.
Adam Reich has worked as a consultant or speaker for AbbVie, Bioderma, Celgene, Chema Elektromet, Eli Lilly, Galderma, Janssen, Leo Pharma, Medac, Menlo Therapeutics, Novartis, Pierre-Fabre, Sandoz, and Trevi, and participated as principal investigator or subinvestigator in clinical trials sponsored by AbbVie, Arcutis, Drug Delivery Solutions Ltd, Galderma, Genentech, Janssen, Kymab Limited, Leo Pharma, Menlo Therapeutics, MetrioPharm, MSD, Novartis, Pfizer, and Trevi. Diana Wolańska-Buzalska is an employee of L’Oréal. Barbara Zegarska declare no conflict of interest.

References