Hypothalamic-Pituitary-Adrenal Axis Response in Patients With Acne Vulgaris Treated With Clascoterone.

BACKGROUND: Clascoterone cream 1% is a topical androgen receptor inhibitor approved to treat acne vulgaris in patients =>12 years of age. This report provides details of patients who developed laboratory signs of hypothalamic-pituitary-adrenal (HPA) axis suppression without clinical signs of adrenal suppression during the clascoterone development program. METHODS: Two open-label, multicenter, Phase 2 trials evaluated HPA axis suppression in patients with moderate-to-severe acne vulgaris. Study 1 (NCT01831960) enrolled cohorts of adults =>18 years of age and adolescents =>12 to <18 years of age. Study 2 (NCT02720627) enrolled adolescents 9 to <12 years of age. Patients applied clascoterone twice daily at maximum-exposure dosages for 14 days. Adrenal suppression was evaluated via cosyntropin stimulation test (CST) at baseline and day 14. Patients with an abnormal CST result (serum cortisol level =<18 µg/dL) had a follow-up CST approximately 4 weeks later. Blood was collected for pharmacokinetic analysis. Other safety assessments included adverse events (AEs), physical examination/vital signs, and electrocardiography. RESULTS: Overall, 5/69 clascoterone-treated patients had an abnormal CST result on day 14, including 1/20 adults, 2/22 patients aged =>12 to <18 years, and 2/27 patients aged 9 to <12 years. All patients had normal cortisol levels at follow-up testing approximately 4 weeks later. No relationship was observed between abnormal CST results and clascoterone plasma concentrations or the amount of study drug applied. No clinically relevant AEs or clinically significant changes in safety measures were observed in patients with adrenal suppression. CONCLUSION: Clascoterone induced laboratory evidence of mild, reversible HPA axis suppression under maximum-use exposure. J Drugs Dermatol. 2024;23(6):433-437.     doi:10.36849/JDD.7997.

Comparison of the effect of topical triamcinolone 0.1% cream with sulfur 2.0% cream in the treatment of patients with hand eczema: A randomized controlled trial.

BACKGROUND: Hand eczema (HE) is a common and heterogeneous condition. It has a wide range of etiologies and clinical manifestations. In this study the efficacy of triamcinolone 0.1% cream and sulfur 2% creams was compared in treating patients with HE. METHODS: This randomized, triple-blind clinical trial was performed on 70 patients with HE (including 70 right and 70 left hands). In this study, two creams were used including triamcinolone 0.1% and sulfur 2.0%. Patients were treated with these creams twice a day (once in every 12 h) for 4 weeks. Follow-up was 4 weeks after treatment. Hand Eczema Severity Index (HECSI), itching, dryness, burning sensation, and erythema scores were collected three times during the study and compared between treatment regimens. RESULTS: Findings showed that both triamcinolone (0.1%) and sulfur (2.0%) creams could significantly reduce the scores of HECSI, itching, dryness, burning sensation, and erythema, and the therapeutic effects lasted for at least 4 weeks after cessation of topical treatment. CONCLUSION: Topical sulfur cream (2.0%) is as effective as triamcinolone (0.1%) cream in treatment of HE without any prominent adverse reactions.

Comparison of efficacy and safety of tretinoin 0.05% and glycolic acid peeling 70% in axillary and neck lesions of acanthosis nigricans: A single-blinded, randomized trial.

BACKGROUND: Acanthosis nigricans is a non-inflammatory skin pigmentary disorder characterized by a dark, velvety appearance, primarily observed in the neck and axillary areas. It is commonly associated with obesity, diabetes, and insulin resistance. Although the primary treatment is correcting the underlying disorders, many aesthetic modalities have been established to improve appearance owing to cosmetic concerns. AIMS: We aimed to compare and investigate the effectiveness and side effects of tretinoin 0.05% and glycolic acid 70% in treating acanthosis nigricans lesions of the axillary and neck area. METHODS: This single-blinded, randomized trial recruited patients with neck or axillary involvement. Each patient was randomized to use cream tretinoin 0.05% every other night on one side, while the other side was treated with glycolic acid 70%, which was applied every 2 weeks at the clinic for four consecutive sessions. The study duration was 8 weeks, and patients were evaluated every 2 weeks based on their response to treatment, satisfaction, and side effects. RESULTS: Thirty patients, including 14 with neck lesions and 16 with axillary lesions, were included. Tretinoin was significantly more effective for axillary lesions in terms of treatment response and patient satisfaction (p = 0.02 and p = 0.008, respectively). It was also shown that as the severity of the lesions increased, the response to treatment and patient satisfaction decreased, specifically when treating axillary lesions with glycolic acid (p = 0.02 and p = 0.03, respectively). CONCLUSION: Neither method was significantly effective for neck lesions. However, tretinoin 0.05% was shown to be more efficacious in treating axillary lesions of acanthosis nigricans, despite causing minimal side effects.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

OBJECTIVE: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. METHODS: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. RESULTS: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. CONCLUSION: ZER demonstrated significant potential as a skin-lightening agent.

Efficacy of a moisturizing cream and facial mask for alleviating skin problems associated with medical mask use: A half-face, randomized controlled study.

BACKGROUND: Prolonged use of medical masks has increased skin-related issues. AIM: To evaluate the efficacy of a facial cream and facial mask in mitigating medical mask related skin symptoms. METHODS: Healthy women were randomly assigned to apply a facial cream (n = 32) or a facial mask plus a facial cream (n = 32) on half-faces after wearing medical masks for 4 h (Tb). Transepidermal water loss (TEWL), dryness score, and redness area were assessed at Tb and 10 min after using the cream (T1) in the facial cream group, and at Tb, 1 h after using the facial mask (T2), and 10 min after using the cream (T3) in the combined use group. RESULTS: In the facial cream group, the treated half-face showed significantly better improvements from Tb to T1 in TEWL (-2.95 ± 0.38 vs. -0.68 ± 0.35 g/h·cm2, p < 0.001) and skin dryness score (-1.00 ± 0.12 vs. 0.00 ± 0.00, p < 0.001). In the combined use group, the treated half-face showed significantly better improvements from Tb to T2 and T3 in TEWL (T2, -3.46 ± 0.33 vs. -0.09 ± 0.13 g/h·cm2; T3, -4.67 ± 0.31 vs. -0.28 ± 0.22 g/h·cm2) and skin dryness score (T2, -0.63 ± 0.13 vs. 0.03 ± 0.03; T3, -0.94 ± 0.17 vs. 0.19 ± 0.07) (all p < 0.001) then the untreated half-face. The combined use group had significantly lower TEWL at T3 than T2 (p < 0.05). The reduction in redness area was similar between the treated and untreated half-faces in both groups. CONCLUSIONS: The test facial cream and mask significantly improved skin barrier function and alleviated dryness symptoms associated with medical mask use, with the combined use offering superior benefits.

Efficacy of ceramides and niacinamide-containing moisturizer versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris: A split face, double-blinded, randomized controlled trial.

INTRODUCTION: Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. METHODS: This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. RESULTS: CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. CONCLUSION: Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.

Combination of 5% cysteamine and 4% nicotinamide in melasma: Efficacy, tolerability, and safety.

BACKGROUND: Melasma is a chronic dermatosis that impacts the patient's quality of life and can present considerable challenges in terms of effective treatment. OBJECTIVE: To evaluate the effectiveness, tolerability, and safety of 5% cysteamine combined with 4% nicotinamide in female subjects with melasma. METHODS: This single-center, single-arm, prospective, open-label study evaluated patients with melasma using a combination cream of 5% cysteamine and 4% nicotinamide in a progressive regimen (60 min in the first month, 120 min in the second month, and 180 min in the third month). RESULTS: Overall, 35 treated subjects exhibited reduced modified Melasma Area and Severity Index (mMASI) (p < 0.001) and decreased MelasQoL scores (p < 0.001), accompanied by improved brightness, luminosity, homogeneity, and spot intensity (p < 0.001). Photographic and colorimetric analysis revealed smaller spots and improved homogeneity. LIMITATIONS: Adherence to progressive daily treatment could not be evaluated long-term. CONCLUSION: A combination cream comprising 5% cysteamine and 4% nicotinamide was effective, tolerable, and safe for treating melasma.

Jacquet erosive dermatitis associated with commercial barrier cream.

Jacquet erosive dermatitis (JED) is a rare, severe form of napkin dermatitis associated with friction and irritant exposure in the napkin area. The condition typically causes erosions and erythematous punched-out ulcerations. We present two cases of JED in infants associated with the use of a common brand barrier cream Curash. This appeared to present following a change of several active ingredients.

Long-Term Safety and Efficacy of Twice-Daily Topical Clascoterone Cream 1% in Patients Greater Than or Equal to 12 Years of Age With Acne Vulgaris.

BACKGROUND: Clascoterone cream 1% is approved for the treatment of acne vulgaris in patients aged ≥ 12 years based on results from two 12-week Phase 3 studies in patients with moderate-to-severe acne. Safety and efficacy of clascoterone in patients aged ≥ 12 years from an open-label, long-term extension study are presented.  Methods: Enrolled patients applied clascoterone cream 1% twice daily to the entire face and, if desired by the patient and/or investigator, truncal acne, for up to 9 months. Patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) could stop treatment and resume if/when acne worsened. Safety was assessed from treatment-emergent adverse events (TEAEs) and local skin reactions (LSRs [telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/burning, and pruritus]) in all treated patients. Efficacy was assessed from IGA at each visit among those completing the study per-protocol (PP); face and trunk were evaluated individually.  Results: Of 600 patients aged ≥ 12 years (original randomization: 311 clascoterone, 289 vehicle), 343 completed the extension study (177 clascoterone, 166 vehicle). There were 187 TEAEs in 108/598 clascoterone-treated patients (18.1%), including 56/311 (18.0%) and 52/287 (18.1%) patients originally randomized to clascoterone and vehicle, respectively; the most common LSRs (previous clascoterone/vehicle) were erythema (face, 8.0%/7.7%) and scaling/dryness (face, 10.0%/7.3%). The percentage of PP patients with facial and truncal IGA 0/1 increased to 48.9% (156/319) and 52.4% (65/124), respectively, at study end. CONCLUSIONS: Clascoterone cream 1% maintained a favorable safety and efficacy profile for up to 12 months in patients aged ≥ 12 years. Eichenfield LF, Hebert AA, Stein Gold L, et al. Long-term safety and efficacy of twice-daily topical clascoterone cream 1% in patients ≥ 12 years of age with acne vulgaris. J Drugs Dermatol. 2023;22(8):810-816. doi:10.36849/JDD.7592.

Individual Article: Clascoterone Cream 1%: Mechanism of Action, Efficacy, and Safety of a Novel, First-in-Class Topical Antiandrogen Therapy for Acne.

Acne is a prevalent chronic inflammatory disease that can cause severe psychiatric effects and physical scarring of the skin. Historically, although systemic antiandrogen acne medications have been effective in women, the utility of these systemic medications has been limited due to potential systemic side effects in men and pregnant women. Therefore, research has been focused on developing topical formulations of antiandrogen therapy for acne. Topical clascoterone cream 1% is the first topical anti-androgen medication approved for the treatment of acne vulgaris in patients 12 years and older and represents a breakthrough in acne treatment. Clascoterone, or cortexolone-17α propionate, is an androgen receptor inhibitor with highly localized activity. Thismedication is thought to compete with dihydrotestosterone (DHT) for androgen receptors located in pilosebaceous units, thus inhibiting the acnegenic downstream effects of DHT such as lipid synthesis and inflammatory cytokine production in a dose-dependent manner. Two phase III clinical trials have been conducted thus far; both trials have shown clascoterone 1% cream applied BID to be significantly more effective than placebo cream at treating acne vulgaris in patients ages 12 and older with moderate-to-severe acne. Clascoterone has also been shown to have a similar safety profile to that of placebo cream in clinical studies, without any systemic antiandrogenic effects observed in the clinical setting. Due to its novel mechanism of action and activity limited to the skin, clascoterone presents an exciting opportunity for dermatologists to further optimize care for eligible acne patients, either as a monotherapy or in combination with other anti-acne medications. J Drugs Dermatol. 2023;22:56(Suppl 1):s7-14.

Dermal Safety of Tapinarof Cream 1%: Results From 4 Phase 1 Trials.

BACKGROUND: Tapinarof (VTAMA®; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under investigation for atopic dermatitis treatment as a 1% cream formulation for once-daily (QD) application. OBJECTIVE: Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions. METHODS: We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity. RESULTS: 376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials. CONCLUSIONS: Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults. TRIAL REGISTRATION: IND 104601 J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627R1.

Efficacy and Safety of Tazarotene 0.045% Lotion in Caucasian Adults With Moderate-to-Severe Acne.

BACKGROUND: While topical retinoids are a mainstay of acne treatment, acne can manifest differently in various skin types. The objective of these post hoc analyses from two pooled phase 3 studies was to examine efficacy and safety of tazarotene 0.045% and quality of life improvements in self-identified Caucasian adults with moderate-to-severe acne. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion (N=1,614); a subset of adults (≥18 years) who self-reported Caucasian (White) race (n=645) were examined. Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment (endpoint) success (≥2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear]). Quality of life, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were also assessed. RESULTS: At week 12, tazarotene lotion significantly reduced lesion counts by ~60% (least-squares mean percent changes from baseline, tazarotene vs vehicle: inflammatory, -61.2% vs -51.1%; noninflammatory, -59.7% vs -49.3%; P<0.001, both). Significantly more participants achieved treatment success with tazarotene lotion versus vehicle (P<0.001). Numerical improvements in quality-of-life domains were observed from baseline to week 12. Most TEAEs were unrelated to treatment, and rates of moderate-to-severe erythema decreased from baseline to week 12 with tazarotene treatment. CONCLUSIONS: Tazarotene 0.045% lotion was efficacious and well tolerated over 12 weeks and led to quality-of-life improvements in Caucasian adults with moderate-to-severe acne. These results, along with those from patients with skin of color, demonstrate that once daily tazarotene 0.045% lotion is an effective and well-tolerated treatment option regardless of race or skin color.J Drugs Dermatol. 2022;21(10):1061-1069. doi:10.36849/JDD.6834.