A novel moisturizer with high sun protection factor improves cutaneous barrier function and the visible appearance of rosacea‐prone skin

Summary Background Consensus guidelines advocate general skincare for rosacea patients. Objectives Two independent studies were performed to assess whether a tinted daily SPF‐30 facial moisturizer (DFM30) improves barrier function of dry skin and the efficacy and tolerability of DFM30 on rosacea‐prone skin. Methods In study 1, electrical capacitance (EC) and transepidermal water loss (TEWL) were measured at baseline, 2, 4, 8, and 24 hours after a single application of DFM30 and on a control site in 21 healthy females with dry skin. Study 2 evaluated 33 females with mild to moderate rosacea and nontransient erythema. Efficacy and tolerability after once‐daily DFM30 were assessed using a chromameter, image analysis of photographs, and trained rater and patient evaluations up to day 22. Results In study 1, EC showed statistically significant increases at 2, 4, and 8 hours, and TEWL showed statistically significant decreases 2, 4, 8, and 24 hours after DFM30 application to healthy females compared to baseline. In study 2, covering skin redness improved significantly after DFM30 application on day 1; 33.3% showed improved covering skin redness compared to baseline. Patients reported significantly less redness on day 8 than day 3. Feelings of dryness and tightness/tension were lower 30 minutes after first application. Feeling of dryness was lower than baseline after 3 days, 1 and 3 weeks. Image analysis suggested redness was significantly lower on day 22 compared to baseline. Chromameter readings showed significantly lower erythema on the cheek compared to baseline. All patients stated that DFM30 relieves and neutralizes visible redness who also indicated that they would purchase DFM30, and the product was well tolerated. Conclusions These studies show that DFM30 is suitable as part of the skincare regimens advocated by ROSacea COnsensus (ROSCO) for rosacea patients. DFM30 is an effective moisturizer that improves cutaneous barrier function and the appearance of rosacea‐prone skin.


| MATERIAL S AND ME THODS
Two independent studies were conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and local regulatory requirements.
The first study was performed in conformity with the standard Operating Procedures of Institut d' Expertise Clinique. The second study adhered to the protocol and compliance with the quality system of ProDerm. Audits were performed at regular intervals to verify adherence to both study protocols.
In both studies, room humidity and temperatures were maintained within published guidelines 11 and patients or healthy women rested in the room for at least 30 minutes before measurements.
Safety was monitored by reporting of adverse events.

| Study A (cutaneous barrier function)
The first study (performed at IEC France, Lyon) enrolled 21 healthy Caucasian females (age 18-70 years) with dry skin on their inner forearm and an initial moisturization level that corresponded to electrical capacitance values of ≤50 arbitrary units.
Patients with rosacea often present with a defective skin barrier and therefore an increased transepidermal water loss (TEWL). 12,13 Healthy subjects with dry skin were used in order to "mimic" the damaged barrier and increased TEWL that is found in patients with rosacea. 12,13 Dryness was defined with an objective dermatological assessment of dryness as well as subjective reports from the partici-  The test and control areas were 20 cm 2 areas of dry skin on the inner forearm. A technician applied DFM30 (2 mg cm −2 ) to the test area on the right or left forearm according to randomization and massaged until the product penetrated completely. Electrical capacitance and TEWL were measured at baseline and 2, 4, 8, and 24 hours after a single application of DFM30.
Descriptive statistics summarized the results, and differences were assessed using the Shapiro-Wilk test (significance defined as P < 0.01). Treated and control areas were compared using the Student t test or Wilcoxon test (both two-tail, significance defined as P < 0.05) for normal and nonparametric distributions, respectively.

| Study B (efficacy and tolerability)
The second study (performed at the proDERM Institute for Applied Patients assessed subjective efficacy on these days. Subjective tolerability, technician-evaluated tolerability, and eye status were assessed on day 22. In addition, on day 22, a full-face image was taken and patients rated their agreement with statements about product efficacy and traits. Trained raters and patients assessed skin redness or covering of skin redness using a five-point scale ranging from "None" to "Strong." Raters assessed skin dryness and objective skin status (scaling, fissures, papules, pustules, edema, vesicles, weeping) using this five-point scale. Patients used the same five-point scale to evaluate subjective efficacy, tolerability, and eye status, and rated their agreement with statements about product efficacy and traits using a five-point scale ranging from "Fully agree" to "Fully disagree." Statistical significance was defined as P < 0.05. Rater-assessed outcomes were compared using Wilcoxon signed-ranks test.
McNemar's test was used for worsened and improved assessments.
The Binomial test was used for frequencies of answers between the "agree" and "disagree" groups. Instrumental measurement parameters were compared using a paired t test.
TA B L E 1 TEWL and electrical capacitance following a single application of DFM30

| Study A (cutaneous barrier function)
Thirty healthy females with dry skin on their inner arm were screened, of which 21 were eligible (mean age 46.0; range 20-68 years). All those enrolled completed the study. Figure 1 and Table 1

| Study B (efficacy and tolerability)
Thirty-three females (mean age 53.7 ± 10.4 years) were enrolled of which three did not complete the study for reasons that were not associated with DFM30. Thirty patients self-reported having sensitive skin.
No statistically significant differences were found for skin redness ( Image analysis suggested that skin redness (Table 3)  After the first application of the DFM30 and on day 22, significantly more patients agreed with all statements regarding its product traits and efficacy than disagreed (Table 4). After 3 weeks, the

| D ISCUSS I ON
The ROSCO guidelines note that education and instruction about general skin care is "essential" for all patients with rosacea to ensure the best possible treatment outcomes. Elements in skincare include sunscreen, frequent use of moisturizers and gentle over-the-counter cleansers, and avoiding known triggers. Indeed, general skincare is the main management strategy for the secondary features of rosacea. 8 The two studies presented in this paper show that the DFM30 is suitable as part of the skincare regimens advocated by ROSCO for rosacea patients, enhances cutaneous barrier function, and improves the visible appearance of rosacea-prone skin. patients with rosacea often present with a defective skin barrier and therefore an increased TEWL. Accordingly, subjects with dry skin on the forearms were used to replicate the damaged barrier and increased TEWL that is found in such patients. 12,13 These enhancements in skin function seem to translate into improved outcomes in patients with type I rosacea and mild to moderate nontransient erythema. DFM30 is tinted, and 30 minutes after the first application, assessments by the patient and the rater showed a camouflage effect, which was confirmed by chromameter measurements on the cheek. Image analysis, however, did not confirm a reduction in visible redness. The reasons for the discordance between the assessment methods are unclear but may be related to interference by the pigment included in the product with the measurement system.
Subjective assessment showed no reduction of skin redness after 1 and 3 weeks of application. This suggests that camouflage associated with the tinted formulation was responsible for the anti-redness effect. However, rosacea patients reported significantly less redness on day 8 compared to day 3. Image analysis showed a significantly reduced skin redness on day 22 compared to baseline on the nonaffected forehead. As this was an exploratory study, the statistical analysis did not account for multiple observations and these may be type 1 errors.
The chromameter measurements on the cheek indicated improved erythema at all times compared to baseline. After correcting using data obtained from the control area (forehead), the results were confirmed. However, the effect on day 22 just missed significance (P = 0.078), suggesting a larger study may be warranted.
Therefore, the study could be repeated in a larger number of patients using statistical analysis of multiple observations.
Patients showed a strong agreement with statements about favorable traits and attributes, suggesting that DFM30 would be an The product reduces the feeling of discomfort 6.7 30.0 63.3 9.5 90.5 <0.001 The product helps conceal skin redness immediately 6.7 6.7 86.7 7.1 92.9 <0.001 The product can be used as an alternative to makeup due to the tinted coverage The product is easy to apply 3. While these results show that DFM30 is effective and well tolerated, the studies had certain limitations and raised further suggestions for additional investigations. As mentioned above, the study could be repeated in a larger number of patients using statistical analysis of multiple observations. Each of the studies was performed at one center. They could be replicated in a larger, more diverse sample including men, more diverse skin types and the different phenotypes of rosacea. The benefit against UV/sun exposure could also be assessed in a "naturalistic" study, conducted in a natural setting, and the TEWL and skin conductance study replicated on patients with rosacea.

| CON CLUS IONS
The two studies in this paper show that DFM30 is suitable as part of the skincare regimens advocated by ROSCO for patients with rosacea. In healthy females presenting with dry skin on their forearms, a single application of DFM30 produced a statistically and clear moisturization effect that persisted for 8 hours.
DFM30 also decreased in TEWL about 24 hours later, suggesting strengthening of barrier function. This finding was confirmed by clinical observation that DFM30 improved dryness in the rosacea patients.
These improvements in skin function seem to translate into improved outcomes in patients with type I rosacea and mild to moderate nontransient erythema. DFM30 is tinted, and 30 minutes after the first application, assessments by the rosacea patients and the rater showed a camouflage effect. Patients agree that the product's traits and attributes could be appropriate for a skincare product for rosacea. All rosacea patients stated that they would like to purchase the product. Taken together, these results show that DFM30 is an effective and well-tolerated moisturizer that improves cutaneous barrier function and the visible appearance of rosacea-prone skin.

ACK N OWLED G M ENTS
Medical writing and editorial services were provided by MedSense Ltd and Mark Greener, funded by Galderma Research and Development.

CO N FLI C T S O F I NTE R E S T
NL and FS are employees of Galderma R&D Egerkingen, Switzerland.
HB serves as an advisor, investigator or on the speaker's bureau for Galderma, Ortho Dermatologic, Bayer, L'Oreal and La Roche-Posay.

ST is an employee of Galderma Research & Development, Sophia
Antipolis, France.