Abstract
Acne vulgaris (AV) is a common skin condition that can cause substantial psychosocial impact. Treatments of AV target clearing and prevention of lesions and reducing scarring and dyspigmentation. Numerous medications are used to target one or more of the pathogenetic factors contributing to AV. The irritative potential of acne products and their tolerability are important aspects that may affect patient adherence to therapies. Adjunctive skincare products offer several benefits to acne-prone skin, by reducing redness, inflammation, and discomfort and improving skin texture. In addition, complementing AV prescription interventions reduces the time to healing of lesions, the extent of scarring, and the number and severity of breakouts. This multicentre, open-label, single-cohort study evaluated the use of ceramide-containing hydrating cream-to-foam cleanser and facial moisturizing lotion for improving topical treatment tolerability and adherence in facial acne. Combining a proper skincare regimen with acne treatments may help decrease their irritating potential and support the skin barrier, which can improve treatment adherence and ultimately, treatment outcomes.
Introduction
Acne vulgaris (AV) is a common skin disorder and one of the most burdensome. 1 It is characterized by chronic inflammation of the pilosebaceous unit that causes noninflammatory and inflammatory lesions and scarring. AV starts in childhood but can persist into adulthood, affecting up to 15% of women. Emotionally, AV can cause embarrassment, self-consciousness, anxiety, and depression. Treatments of AV treatment target the clearing and prevention of lesions and reducing scarring and dyspigmentation, therefore improving the quality of life (QoL) of affected individuals.1,2
Numerous topical medications are used to target one or more of the pathogenetic factors contributing to AV. Many topical AV treatments are characterized by keratolytic activity (eg, retinoids, benzoyl peroxide, salicylic acid), which can impair the skin barrier and increase transepidermal water loss, thus decreasing skin hydration2,3 Furthermore, many acne treatments have been associated with skin irritation. The irritative potential of topical acne products and their tolerability is an important aspect that may affect patient adherence to prescribed therapies in real-world practice. Combining a proper skincare regimen (ie, gentle cleanser, moisturizer) with acne treatments may help to decrease their irritating potential, which may, in turn, improve treatment adherence and ultimately, treatment outcomes. 4
Retinoids are a class of keratolytic drugs derived from retinoic acid that are used for the treatment of AV. They are comedolytic and anti-inflammatory5-8 Topical retinoids are an integral component of acne therapy and are considered first-line treatments, alone or in combination with antimicrobials, for all but the most severe acne cases6,7 These drugs are potentially irritating to the skin, with common adverse events (AEs) such as dryness, erythema, stinging, and pruritus, especially in the first several weeks of treatment.8,9 However, formulation advances have evolved to lessen the inclusion of potentially irritating surfactants, preservatives, alcohol, and parabens to improve tolerability.10,11
In this multicentre, open-label, cohort study, we evaluate the effect of a ceramide-containing cleanser (CeraVe Hydrating Cream-to-Foam Cleanser) and moisturizer (CeraVe PM Facial Moisturizing Lotion) on acne treatment tolerability and adherence.
Materials and Methods
Subjects
In all, 137 subjects were enrolled in this multicentre, open-label, cohort study. After signing an informed consent, all enrolled subjects received an unblinded investigational product (IP). This was a single cohort study, with no placebo or randomization schedule. Subjects participated in the study for approximately 3 months from the time they enrolled through the end of the study visit. There was no formal sample size calculation for this study. The sample size was based on clinical considerations and not statistical power calculations.
Ethical Approval and Consent
The study protocol as well as the consent forms and all scales were approved by an IRB committee (REBs were the Canadian SHIELD Ethics Review Board and the Health Research Ethics Board of Alberta.
All adult subjects and young subjects’ parents/guardians or legal representatives provided written consent after a detailed explanation of all parts of the study. Consent included publication of individual patient images and case details.
Study Endpoints
Primary: Safety
The primary endpoint was the determination of IP safety, as measured by the frequency of adverse events (AE) and study adverse events (SAE) reported by investigators as being possibly or probably related to the IPs.
Secondary: Efficacy
The secondary endpoint was the determination of the efficacy of the IP as measured by the following scales:
- Investigator Global Assessment (IGA) acne scale: a commonly used tool in dermatological research to evaluate the severity of skin conditions, particularly those related to inflammatory skin diseases such as acne. IGA is primarily used by healthcare providers or trained investigators to assess the overall severity of a patient’s condition based on clinical examination. It is rated on a scale from 0 (clear) to 5 (severe).
- Global Aesthetic Improvement Scale (GAIS): a standardized tool used to assess overall improvement in aesthetic appearance commonly employed in dermatology. In clinical practice settings, it is a subjective rating scale that allows both patients and healthcare providers to assess changes in aesthetic outcomes. It typically consists of a series of categories or descriptors that quantify the degree of improvement observed after treatment.
- Physician-assessment irritated and dry skin (IDS): an assessment tool used by healthcare providers to evaluate the severity of dryness and irritation of the skin in patients, particularly those with dermatological conditions. IDS typically involves a standardized evaluation conducted by a physician focusing on specific signs and symptoms of dry and irritated skin. The assessment is rated on a scale from 0 (Clear) to 4 (Severe).
- Transepidermal water loss (TEWL) by way of corneometry: it is the most used objective measurement for assessing the skin water barrier function. 12 In the case where the skin barrier is disrupted, we see an increased TEWL. Due to a scarcity of specialized equipment, personnel training, and other resources, only 2 sites participated in the collection of TEWL measurements.
Exploratory
The exploratory endpoints were the effect of the IP use on QoL. Assessing the QoL for individuals with acne is crucial as it provides insights into the emotional, psychological, and social impacts of the condition. Measurements were rated on a scale from 0 (very much) to 3 (not at all).
Inclusion and Exclusion Criteria
Inclusion criteria
Male and female subjects of all ethnic/racial backgrounds were eligible for enrolment. Subjects had to be 12 years and older or had parent/guardian or legal representative consent for participation if less than the age of majority (18 or 19 years old), which differed depending on the home province.
Subjects must have had a previous or current clinical diagnosis of mild-to-moderate acne at the time of enrolment. Subjects were treatment naïve or had initiated use of a prescribed topical retinoid or oral treatment except isotretinoin, that is, commercially available and approved for use in Canada, within the 2 weeks prior to enrolment. Prescription details (eg, dose, frequency of use) were left to the discretion of the investigator.
Subjects who were prescribed a topical acne treatment more than 2 weeks prior to study enrolment were only eligible if there was a change in the strength of the medication (eg, dose, frequency of use) within 2 weeks of study enrolment.
For the duration of the study, subjects agreed to refrain from undergoing any aesthetic or dermatological treatment. No female subjects were pregnant and agreed to refrain from becoming pregnant for the duration of the study.
Exclusion criteria
Subjects were ineligible for study enrolment if they were currently undergoing treatment with isotretinoin, or within 3 months prior. Those with severe acne were excluded from the study. Subjects were excluded from the study if they had hypersensitivity to any of the ingredients contained within the investigation products (IP) or a history of severe allergies manifested by anaphylactic shock or the need for an epinephrine autoinjector (eg, EpiPen®).
Investigational Product
The IPs used in the study were provided by CeraVe. Descriptions of the IPs were presented in Figures A1 and A2. The investigational products were labelled as per the manufacturer’s packaging. Products had to be used prior to the expiration date printed on the package if listed.
Treatments
Two treatment groups were evaluated: one group used only the IP products and another group used IPs in addition to their prescribed acne medication(s). Subjects were instructed to use the cleanser once daily and the moisturizer twice daily throughout the trial.
Study procedures
All clinical assessments were conducted by the principal investigators.
Subjects completed a total of 4 study visits, over 3 months, as follows:
Visit 1: Screening and Baseline.
Visit 2: Week 4 (±3 days)
Visit 3: Week 8 (±3 days)
Visit 4: Week 12 (±3 days).
A self-reported questionnaire was completed at each visit to determine adherence to prescribed medication usage and adherence to IPs.
Statistical Analyses
IBM SPSS Statistics (Version 29.0) was used for all data analyses. All evaluations were considered in the assessment of efficacy. Scaled variables are displayed as means ± SD. A paired T-test or ANOVA was used to analyze skin conditions by comparing the baseline (Day 0) versus all follow-up visits. Categorical data were presented by frequency (%) values or cross-tabulations. Tests were carried out at the 5% significance level (P
Results
Demographics
Seven Canadian sites participated in the study. In total, 141 subjects were screened and 137 met all inclusion criteria and were subsequently enrolled. Due to dropouts or missing visits, the sample size varied at each timepoint (Table 1). Efficacy and safety data were performed on the full data set. The demographic distribution of the sample is presented in Table 2. The average age was 24.16 years (SD: 7.92).
Sample Size at Each Visit. One Hundred Forty-One Subjects were Screened and 137 Met All Inclusion Criteria at the Baseline and were Enrolled. Due to Dropouts or Missing Visits, the Sample Size for Each Subsequent Visit varied.
Demographics of the Sample Population (N = 137). The Gender and Ethnicity Distribution Across the Studies Population.
Treatment
Most subjects (N = 99; 72.8%) were treatment naïve prior to enrolling in the trial. Fifty-seven (41.6%) were not prescribed a concomitant medication for acne throughout the trial and instead used only the IPs for treatment. The remaining subjects (N = 38; 27.7%) had a recent (ie, within 2 weeks of enrolment) change in their acne medications (eg, increased dose) (Table 3, Figure 1).
Acne Medications Prescribed to the Sample Population at BASELINE (N = 137). Frequency of People Taking Various Acne Medication Across the Studies Population.
Picture of the progress of 4 participants with IP and treatment. (A) Age 21, male, IP + treatment. (B) Age 13, female, IP + treatment. (C) Age 17, female, IP + treatment. (D) Age 17, female, IP + treatment. IP, investigational product.
Safety Data—Primary Endpoint
Throughout the trial, there were 19 AEs reported by the principal investigators (Table 4). Eleven of these were reported to be possibly or probably related to the prescription medications. There were no AEs, SARs, UAEs, or SAEs reported to be possibly or probably related to the IPs.
Adverse Events Reported Throughout the Trial.
Transepidermal Water Loss
TEWL data were collected on 54 subjects on retinoids + IP or IP only. TEWL did not significantly change from baseline at any visit suggesting a protective effect of the IPs on retinoid-induced AEs. ANOVA [F(3, 1179) = 0.230, P = .876] (Figure 2).
TEWL assessment across visits. TEWL did not significantly change any visit when compared to the baseline visit. TEWL, transepidermal water loss.
Subject-Assessed QoL
Sum scores for the QoL were compared between Baseline and follow-up visits. QoL did not significantly change since baseline, at any visits, ANOVA [F(3, 548) = 61.60, P = .225] (Figure 3).
QoL assessments across the visits for all groups combined. No significant change in the QoL was observed throughout the study visits. QoL, quality of life.
Global Aesthetic Improvement Scale
The GAIS is rated on a scale from −1 (worse) to 3 (Very much improved). Sum scores were compared between baseline and follow-up visits. In our study, the primary efficacy endpoint was the investigator-assessed GAIS at Visit 4.
Based on the investigator-assessed GAIS, results were maximal at Week 12. Results continued to improve as the duration of use of prescription medication and/or IPs increased over time. At Week 4, 89.2% of subjects reported they are improved, much improved, or very much improved in global aesthetic appearance; at Week 8, 91.4% of subjects reported they are improved, much improved, or very much improved in global aesthetic appearance; and at Week 12, 93.6% of subjects improved, much improved, or very much improved in global aesthetic appearance (Figure 4). Those results were observed in the IP-only group (Figure 7A) and the IP + retinoid group (Figure 8A).
GAIS representation for all groups combined across the visits as compared to baseline. The sum of scores that showed maximal improvement at Week 12 was compared between baseline and follow-up visits. In our study, the primary efficacy endpoint was the investigator-assessed GAIS at Visit 4. GAIS, Global Aesthetic Improvement Scale.
Physician-Assessed IGA
A chi-square test of independence was performed to examine the relation between IGA score and visit. The relation between these variables was significant, X2 (9, N = 520) = 209.95, P < .001, with acne severities lessening over time (Figure 5). Those results were observed in the IP-only group (Figure 7B) and the IP + retinoid group (Figure 8B).
IGA scores for all groups combined across the visits. The scores were significantly different across the visit with acne severities decreasing over time. IGA, Investigator Global Assessment.
Physician-Assessment of IDS
Sum scores were compared between baseline and follow-up visits for the IDS. Based on the results of an ANOVA [F(3, 478) = 64.28, P < .001], all parameters of the physician assessment of dry and irritated skin (ie, roughness, flakes/scales, dehydration, inflammation) significantly improved since baseline, at all visits [(P < .001)] (Figure 6). However, improvements in symptoms were maximal at Week 12. The effect size, eta squared (η²), was 0.29, indicating a large effect (Figure 5). Those results were observed in the IP-only group (Figure 7C) and the IP + retinoid group (Figure 8C).
IDS sum of scores was compared between baseline and follow-up visits. All parameters of the Physician-assessment of Dry and Irritated Skin (ie, roughness, flakes/scales, dehydration, inflammation) significantly improved compared to the baseline visits with maximal results observed at Week 12. IDS, irritated and dry skin.
Representation of the different endpoint measurements in the IP-only group: (A) GAIS, (B) IGA, (C) IDS. IP, investigational product; GAIS, Global Aesthetic Improvement Scale; IGA, Investigator Global Assessment; IDS, irritated and dry skin.
Representation of the different endpoint measurements in the IP + retinoid group: (A) GAIS, (B) IGA, (C) IDS. IP, investigational product; GAIS, Global Aesthetic Improvement Scale; IGA, Investigator Global Assessment; IDS, irritated and dry skin.
Discussion
AV treatment can be associated with various adverse events. Cutaneous effects may include dryness, irritation, redness, and sensitivity. However, the use of hydrating and cleansing formulations alongside prescribed acne medication(s) can mitigate these concerns which often contributes to patient adherence and ultimately treatment outcomes. This study was designed to test the effect of a ceramide-containing cleanser and moisturizing lotion on enhancing topical treatment tolerability in facial acne.
Positive Effect of Topical AV Treatment Combined with IP
The skin barrier acts as the body’s first line of defence against external pathogens, irritants, and pollutants. When the barrier is compromised, it can lead to inflammation and infection, both of which are key factors in acne formation. An impaired skin barrier function in patients with AV is marked by a reduction of ceramides, which may be associated with comedone formation.3,13-15 AV is associated with higher TEWL values. 16 In addition, prescribed therapies used to treat AV can disturb the skin barrier and increase TEWL.2,3 In this study, the lack of significant change in TEWL across the visits suggests a protective effect of the IPs on retinoid-induced AEs.
In addition, the severity of skin conditions, dryness, and irritation significantly improved in the group using both topical treatment(s) and IPs even though the group only using the IPs showed improvement as well. This suggests that the IPs played a role in improving acne symptoms and may have a protective role in reducing TEWL in combination with the use of topical medications, to optimize its effect on the acne symptoms while reducing AEs. Integrating hydrating and cleansing formulations into a skincare routine can provide significant protection against these side effects. Hydrating creams help to soothe and moisturize the skin, reducing dryness, redness, and peeling commonly associated with acne treatments. In addition, the barrier function provided by these creams helps protect the skin from environmental aggressors and further irritation. Cleansing creams help maintain the skin’s cleanliness and barrier integrity, reducing the risk of bacterial infections and inflammation. By removing dirt, oil, and makeup residue, cleansing creams prevent pore blockages and flare-ups, promoting clearer and healthier-looking skin. In addition, some cleansing creams contain ingredients with anti-inflammatory properties, further soothing signs of skin irritation such as redness.
All factors related to the prescribed treatment of AV such as skin roughness, presence of flakes/scales, presence of erythema, skin dehydration, and inflammation of non-acne skin showed significant improvement in the group taking retinoid and IP combined. Even though the percentage of improvement for the group taking only IP was not negligible, it was only statistically different in the retinoid + IP group. These results are expected since topical AV medications are proven in acne management, but our results support the importance of a proper skincare regimen to improve treatment tolerability, skin appearance, and AV symptoms.
The IPs Provide a Protective Effect When Combined with Topical AV Treatment
Hydration plays a crucial role in maintaining healthy skin. When using acne medications, which often strip the skin of its natural oils, maintaining adequate hydration levels becomes even more critical. Hydrating creams are formulated to replenish moisture levels in the skin, preventing dryness and flakiness commonly associated with acne treatments. By providing hydration, these creams help maintain the skin’s integrity and barrier function, reducing the likelihood of experiencing severe side effects. Proper cleansing is essential, especially for individuals undergoing acne treatment. Acne medications can increase the skin’s sensitivity and susceptibility to irritation, making it crucial to cleanse gently and effectively. Cleansing creams designed for sensitive or acne-prone skin can help remove impurities and excess oil without stripping the skin of its natural moisture. By keeping the skin clean and free of debris, cleansing creams minimize the risk of clogged pores and breakouts, which are common concerns during acne treatment.
Combining a proper skincare regimen (ie, cleanser, moisturizer) with acne treatments may help to decrease their irritating potential, which may, in turn, improve treatment compliance and ultimately, treatment outcomes. 4
The impact of acne on QoL can vary greatly from person to person. Some individuals may experience significant psychological distress and a decrease in their overall QoL due to acne and acne treatments. Acne can affect a person’s self-esteem, social interactions, and overall mental well-being. It may lead to feelings of embarrassment, self-consciousness, and even depression or anxiety in some cases. In addition, the physical discomfort associated with acne lesions and the potential for scarring can further impact QoL. Treatment options for acne, ranging from over-the-counter products to prescription medications and procedures, aim not only to improve the physical appearance of the skin but also to alleviate the emotional burden and improve QoL for individuals affected by acne. In severe cases where acne significantly impacts QoL, healthcare professionals may recommend psychological support in addition to medical treatment. 4 It is interesting to note that the QoL results showed no significant effect in both groups (IP and IP+ prescribed medication), and this suggests a role of the IPs in improving the overall symptoms of AV that can have a detrimental effect on the QoL, as well as a protective effect of the IPs on adverse effects of the retinoid treatment.
GAIS scores in the study showed improvement especially in the last visit (Week 12) indicating a positive effect of the IP on patients’ aesthetic well-being by improving the overall skin condition for IP-only groups and preventing severe AEs for the groups with retinoids and IPs.
Role of the Proper Hydrating and Cleanser Products
When selecting hydrating and cleansing formulations to use as an adjunct to acne prescriptions, it is essential to opt for products that have been specifically evaluated for sensitive or acne-prone skin. Typically, this refers to non-comedogenic and fragrance-free formulas that would not clog pores or cause further irritation. In addition, products that contain soothing ingredients such as aloe vera, hyaluronic acid, and ceramides, can help to hydrate and repair the skin barrier.
Limitations
Our study with an open-label design is unblinded for both the principal investigators and subjects. Subject experiences were self-reported, describing the use, and tolerability of the IP products and/or prescribed acne therapies, where recall bias may impact scores. Without objective monitoring of the use of the IP products (eg, video recording to produce a tracking log of use), it was not impossible to definitively confirm that subjects were fully adherent to the study protocol.
However, the use of IP products with and without prescribed acne therapies reflects real-world settings, increasing the generalizability of study results. Another strength of the study is that any Health Canada-approved topical acne medications could be used for enrolled subjects, which is also reflective of real-world practice. The tolerability evaluation was particularly insightful given our study design as eligibility criteria required subjects having recently started a new topical and/or systemic acne medication (except for isotretinoin) or were undergoing changes to dosing and frequency of use within the last 2 weeks. This eligibility component of the study assessed the true performance of the IP products in serving as an effective adjunct to mitigate potential expected irritating phenomena observed with the use of various topical retinoids.
Conclusion
The potential role of appropriate skin care with gentle cleansers and hydrating moisturizers to mitigate common side effects of acne medications cannot be overstated. By incorporating these skincare products into a daily routine, individuals undergoing acne treatment can minimize dryness, irritation, and other adverse reactions, promoting a restored skin barrier and tolerability to prescribed therapies. Our study results support the use of targeted over-the-counter skin care formulations in managing mild-to-moderate acne, as safe and effective adjuncts to management, and as a sustainable approach to an often chronic and ubiquitous inflammatory skin condition affecting all skin tones and types.
Supplemental Material
sj-tif-1-cms-10.1177_12034754241304729 – Supplemental material for A Multicentre Evaluation of a Ceramide-Containing Hydrating Cream-to-Foam Cleanser and Facial Moisturizing Lotion for Improving Topical Treatment Tolerability in Facial Acne
Supplemental material, sj-tif-1-cms-10.1177_12034754241304729 for A Multicentre Evaluation of a Ceramide-Containing Hydrating Cream-to-Foam Cleanser and Facial Moisturizing Lotion for Improving Topical Treatment Tolerability in Facial Acne by Monica Li, Charles Lynde, Christopher Sibley, Steven C. Bernstein, Steve Mathieu, Lyn Guenther, Nour R. Dayeh and Jerry Tan in Journal of Cutaneous Medicine and Surgery
Supplemental Material
sj-tif-2-cms-10.1177_12034754241304729 – Supplemental material for A Multicentre Evaluation of a Ceramide-Containing Hydrating Cream-to-Foam Cleanser and Facial Moisturizing Lotion for Improving Topical Treatment Tolerability in Facial Acne
Supplemental material, sj-tif-2-cms-10.1177_12034754241304729 for A Multicentre Evaluation of a Ceramide-Containing Hydrating Cream-to-Foam Cleanser and Facial Moisturizing Lotion for Improving Topical Treatment Tolerability in Facial Acne by Monica Li, Charles Lynde, Christopher Sibley, Steven C. Bernstein, Steve Mathieu, Lyn Guenther, Nour R. Dayeh and Jerry Tan in Journal of Cutaneous Medicine and Surgery
Footnotes
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Jerry Tan: COI advisor, consultant, and speaker for L’Oreal Dermatological Beauty. Dr. Monica Li has been a speaker, consultant, and principal investigator to L’Oreal. Dr Nour R. Dayeh: Employee of L’Oreal Canada. Dr. Charles W. Lynde has been a speaker and/or consultant to CeraVe, and a principal investigator to L’Oreal.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Supplemental Material
Supplemental material for this article is available online.
References
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