Top weapons in skin aging and actives to target the consequences of skin cell senescence.

Skin aging has long been considered a purely cosmetic problem. However, as life expectancy increases, skin aging is taking on a functional dimension that goes beyond cosmetics and appearance. Preventive or therapeutic strategies are needed to target cellular senescence, a key process underlying the alterations in skin function and appearance that occur with aging, as well as to address the age-related skin changes associated with 'dermatoporosis' and chronic skin insufficiency/fragility syndrome. Thus, given the need for effective anti-aging products that improve both the appearance and function of the skin, it is essential to distinguish active ingredients that have been proven to be effective, among the large number of available over-the-counter cosmeceuticals. This brief review focuses on a core group of topical actives, describing their clinical effects on senescence and aging, and their molecular mechanisms of action. These actives include hyaluronic acid, which has hydrating and viscoelastic properties and has been shown to reduce skin atrophy; retinaldehyde, which activates retinoid receptors and increases cutaneous elasticity; vitamins C and E, which provide stable oxidative protection; and niacinamide, which reduces inflammation and mitigates the effects of senescence.

Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2).

BACKGROUND: The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti-interleukin-23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are complete. OBJECTIVES: We present 5-year pooled data from reSURFACE 1 and reSURFACE 2. METHODS: reSURFACE 1 and reSURFACE 2 were double-blind, randomized, controlled studies with optional long-term extensions. Adults with moderate-to-severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter [reSURFACE 2 included an etanercept (ETN) arm]. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated. RESULTS: Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure-adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient-years of TIL 100 and TIL 200, respectively. CONCLUSIONS: TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile.

A multicentre, randomized, double-masked, parallel group, vehicle-controlled phase IIb study to evaluate the safety and efficacy of 1% and 3% topical minocycline gel in patients with papulopustular rosacea.

BACKGROUND: Papulopustular rosacea is characterized by chronic facial erythema and inflammatory facial lesions. Minocycline has anti-inflammatory properties which may be effective in the treatment of rosacea inflammatory lesions. OBJECTIVES: To assess the safety and efficacy of once-daily topical minocycline gel 1% and 3% in patients with papulopustular rosacea. METHODS: This was a prospective, 12-week, double-blinded study conducted at 26 sites in the United States; 270 patients with papulopustular rosacea and 12-40 inflammatory lesions were randomized to minocycline 1%, minocycline 3% or vehicle. The primary endpoint was the mean change in inflammatory lesions at week 12. Key secondary endpoints included success on an Investigator's Global Assessment (IGA). RESULTS: Baseline mean lesion counts were 24·6, 25·1 and 24·3 in the minocycline 1%, minocycline 3% and vehicle groups, respectively; at week 12, the counts had decreased by 12·6, 13·1 and 7·9, respectively. Minocycline significantly decreased lesions, compared with the vehicle [P = 0·01, 95% confidence interval (CI) 7·9 to 0·9, for minocycline 1%; P = 0·007, 95% CI 8·3 to 1·3, for minocycline 3%]. The proportion of patients achieving IGA success was 39% in the minocycline 1% arm [P = 0·34, odds ratio (OR) 1·396 and OR 95% CI 0·71 to 2·75 vs. vehicle], 46% in the minocycline 3% arm (P = 0·04, OR 2·03 and OR 95% CI 1·04 to 3·95 vs. vehicle) and 31% in the vehicle arm. CONCLUSIONS: Minocycline topical gel appears to be safe and tolerable at concentrations of 1% and 3%, and both concentrations significantly decreased inflammatory lesion counts, with a significantly larger proportion of patients achieving IGA success at week 12 in the minocycline 3% arm. These findings support further evaluation of minocycline gel for treating inflammatory lesions associated with papulopustular rosacea. Linked Comment: Hampton. Br J Dermatol 2020; 183:412-413.

Long-term safety and efficacy of trifarotene 50 µg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BACKGROUND: Treatment for both facial and truncal acne has not sufficiently been studied. OBJECTIVES: To evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne. METHODS: In a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 µg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET. RESULTS: Of 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit. CONCLUSION: In this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne.

Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND: PF-04965842 is an oral Janus kinase 1 inhibitor being investigated for the treatment of plaque psoriasis. OBJECTIVES: To evaluate the efficacy, safety and tolerability of PF-04965842 in patients with moderate-to-severe plaque psoriasis. METHODS: Patients in this phase II, placebo-controlled study (NCT02201524) were randomized to receive placebo, 200 mg once daily (OD), 400 mg OD or 200 mg twice daily (TD) PF-04965842 for 4 weeks. The primary endpoint was change from baseline in Psoriasis Area Severity Index (PASI) at week 4. Study enrolment was discontinued on 25 June 2015 due to changes in the sponsor's development priorities. RESULTS: Fifty-nine patients were randomized and received at least one dose of PF-04965842 or placebo. The estimated treatment effect (active -placebo PASI change from baseline) and 90% confidence interval at week 4 was -5·1 (-9·2 to -1·0), -5·6 (-9·6 to -1·6) and -10·0 (-14·2 to -5·8) for the 200 mg OD, 400 mg OD and 200 mg TD groups, respectively. At week 4, the proportion of patients achieving PASI 75 was 17% for the placebo and 200 mg OD groups, 50% for the 400 mg OD group and 60% for the 200 mg TD group. There were more abnormal laboratory test results of clinical interest (low neutrophil, reticulocyte and platelet counts) in the 200 mg TD group compared with the OD treatment groups. No serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively, were reported. CONCLUSIONS: These results suggest that treatment with PF-04965842 improves symptoms and is well tolerated in patients with moderate-to-severe psoriasis.

Male skin and ingredients relevant to male skin care.

Male skin care needs are heavily influenced by the need to remove facial hair on a regular basis. Facial skin issues associated with poor hair removal approaches are common and include razor burn and irritation. This paper evaluates current research on shaving technology and how careful ingredient selection can contribute to male skin health. The importance of maintaining hair softness during the shave and restoring facial hydration post-shave is discussed. Data are presented on how post-shave moisturizers containing glycerine and emollients can create an environment for improved barrier function which can be further improved by incorporating specific ingredients such as niacinamide.

Rosacea - global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group.

BACKGROUND: The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. OBJECTIVES: The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. METHODS: The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. RESULTS: New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein-5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein-5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy - the triad of rosacea care - that integrates patient education including psychological and social aspects, skin care with dermo-cosmetics as well as drug- and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. CONCLUSION: The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence-based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.

Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients.

BACKGROUND: Combination therapy utilizing agents with complementary mechanisms of action is recommended by acne guidelines to help simultaneously target multiple pathogenic factors. A unique, topical, fixed-dose combination gel with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has recently been developed for the once-daily treatment of acne. OBJECTIVES: To evaluate the efficacy and safety of adapalene 0.1%-BPO 2.5% fixed-dose combination gel (adapalene-BPO) relative to adapalene 0.1% monotherapy (adapalene), BPO 2.5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris. METHODS: In total, 1670 subjects were randomized in a double-blind controlled trial to receive adapalene-BPO, adapalene, BPO or vehicle for 12 weeks (1 : 1 : 1 : 1 randomization). Evaluations included success rate (subjects 'clear' or 'almost clear'), percentage change in lesion count from baseline, cutaneous tolerability and adverse events. RESULTS: Adapalene-BPO was significantly more effective than corresponding monotherapies, with significant differences in percentage lesion count change observed as early as 1 week. Cutaneous tolerability profile was similar to adapalene. Adverse events were more frequent with the combination therapy (mainly due to an increase in mild-to-moderate dry skin), occurred early in the study, and were transient. CONCLUSIONS: Adapalene-BPO provides significantly greater and synergistic efficacy and a faster onset of action with an acceptable safety profile in the treatment of acne vulgaris when compared with the corresponding vehicle and the adapalene and BPO monotherapies.

The dermatology dispensing debate.

The in-office dispensing of topical skin care products by dermatologists is a source of frequent debate. Guidelines for proper dispensing have been penned by various medical organizations, yet the controversy continues. With the increasing number of physician-dispensed lines available for sale, combined with mounting medical financial issues, the ongoing debate surrounding in-office dispensing will continue.