Benefit of Topical Combination Therapy for Acne: Analyzing Effect Size Using Number Needed to Treat.

BACKGROUND: Topical acne trials often are confounded by high vehicle response rates and differing outcome measures, making it difficult to compare treatments. Number needed to treat (NNT) can be a simple, clinically meaningful way to indirectly compare treatment options without head-to-head data. NNT is the number of patients who need to be treated with an intervention to observe one additional patient successfully achieving a desired outcome versus vehicle/placebo. While treatment attributes such as adverse events may not be captured, lower NNT is a good indicator of a more effective treatment. METHODS: Following a search of combination topical treatments for acne vulgaris, all treatments that reported pivotal trial efficacy data consistent with the 2018 FDA definition of success were included in NNT analyses.  Results: Of 13 treatments, 7 reported 12-week treatment success rates in 11 phase 3 trials, with similar baseline demographics/disease severity. Treatment success ranged from 26.8% with tretinoin 0.1%/benzoyl peroxide (BPO) 3% cream to 50% with triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel. NNTs for the triple-combination gel were 4 and 5 (from 2 pivotal trials). Adapalene 0.3%/BPO 2.5% gel had an NNT of 5. Tretinoin/BPO had the largest range between trials, with NNTs of 4 and 9. The other 4 treatments had NNTs ranging from 6 to 8. CONCLUSION: A comparison of combination topical acne treatment trial data, using the same treatment outcome and similar patient populations, resulted in triple-combination clindamycin phosphate/adapalene/BPO gel and adapalene/BPO gel having the most favorable NNTs.J Drugs Dermatol. 2024;23(2):42-49.  doi:10.36849/JDD.7927.

Objective Evaluation of Skin Sensitivity Across Fitzpatrick Skin Types.

Context: Skin sensitivity may be best defined as self-reported intolerance to application of skincare products. It is commonly believed that individuals with darker skin are generally less sensitive, while those lighter skin are more sensitive. However, there is little objective data correlating sensitivity with skin type or with objective measures of sensitivity. Objective: This study assessed Fitzpatrick skin type and self-reported perception of skin sensitivity. Design: A single-blinded, lactic acid sting test was performed on the medial cheeks, where patients were randomized to receive room temperature 10% lactic acid on the left or right cheek with water applied to the contralateral cheek as a control. Outcome Measures: Stinging was assessed 1 minute after application of test solution to one cheek using a visual analogue scale (VAS). Results: There was a statistically significant difference in self-reported skin sensitivity in patients with Fitzpatrick skin types 1-3 vs 4-6 (73.6% vs 46.5%; P= 0.006). Patients who had higher perceived sensitivity were more likely to have objectively measured sensitivity as well, across all skin types (P<0.01). When stratified by skin type, a numerically higher percentage of subjects with Fitzpatrick skin types 1-3 experienced objective sensitivity compared to subjects with skin types 4-6 (45.6% vs 27.9; P=0.058). Conclusions: Patients with self-perceived skin sensitivity were more likely to develop objective stinging compared to those who did not report sensitivity. Skin sensitivity can occur across all skin types, and patients should be asked about self-perceptions of sensitivity as it is likely an indicator of true sensitivity. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.5880.

The Use of an Over-the-Counter Hand Cream With Sweet Almond Oil for the Treatment of Hand Dermatitis.

Hand dermatitis is estimated to affect greater than 15% of the general population. Childhood eczema, frequent hand washing, and occupational exposure to chemicals are predisposing factors. Hand dermatitis treatment involves both prevention of outbreaks and treatment of active disease. Moisturizers are essential to protect the skin from the environment, enhance hydration, and repair the skin barrier. They have been shown in large studies to prevent occupational related breakouts. Natural oils are commonly used in moisturizers for their moisturizing and emollient properties. Sweet almond oil is an oil that contains high levels of fatty acids and has been used for centuries to treat skin diseases such as eczema and psoriasis. In this study, a moisturizer with 7% sweet almond oil and 2% colloidal oatmeal was found to be both safe and effective in treating patients with moderate to severe hand dermatitis.

J Drugs Dermatol. 2018;17(1):78-82.

Clinical Experience With Once-Daily Dapsone Gel, 7.5% Monotherapy in Patients With Acne Vulgaris.

BACKGROUND: Dapsone gel, 7.5% is a topical medication approved for acne in patients aged 12 years and older. Clinical trials have demonstrated the safety and efficacy of once-daily dapsone gel, 7.5% in patients with moderate acne. OBJECTIVE: The objective of this report is to describe the clinical course of 8 patients who participated in a 12-week program using once-daily dapsone gel, 7.5% as monotherapy for acne in a real-world clinical setting. MONOTHERAPY PROGRAM: Male and female adults and adolescents with facial acne, representing a broad range of ages, skin phototypes, and ethnicities, and with no prior use of dapsone gel, 7.5% applied the product once daily for 12 weeks as monotherapy for acne. Photographs were taken at baseline and at 12 weeks. The treating dermatologists recorded observations of baseline disease, treatment tolerability, and outcomes. An independent rater assessed Global Acne Assessment Score (GAAS) at baseline and at 12 weeks based on photographs. Patients provided testimonials of their experience with treatment. PROGRAM OUTCOMES: Acne improvement was evident in the photographs of the 8 patients. Changes in GAAS at week 12 of treatment, as assessed by an independent rater, ranged from 1- to 3-grade improvement from baseline. CONCLUSION: Photographs, dermatologist reports, and patient commentary in an office-based practice demonstrated that 12 weeks of treatment with only topical dapsone gel, 7.5%, applied once daily, was effective and well tolerated as a stand-alone treatment in 8 patients with facial acne vulgaris, with results that are consistent with the phase 3 pivotal trials. J Drugs Dermatol. 2018;17(6):602-608.

Inflammatory Acne Treatment: Review of Current and New Topical Therapeutic Options.

Acne vulgaris (AV) is an inflammatory skin disease characterized by the presence of comedones, papules, pustules, and nodules. Consensus guidelines recommend the use of combination therapy using different drugs with complementary mechanisms of action to best address as many acne pathogenic factors as possible at the same time. Topical acne medications exist as individual agents that may be combined in physician-recommended regimens or as pre-formulated fixed-dose combination products. In addition, there are several new and promising topical therapies currently being developed that work by different mechanisms of action from traditionally used acne therapies. The following review will cover commonly used drugs, newcomers to the market, and what the future holds for the topical treatment of AV.

Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits.

Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface. SkinMedica's HA5 Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles. Pre-clinical studies demonstrated that HA5 induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA5 application. Initial clinical studies showed that within 15 minutes of application, HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies present in HA5 promotes restoration of endogenous epidermal HA while delivering instant smoothing effects.

Onychomycosis to Fungal Superinfection: Prevention Strategies and Considerations.

Onychomycosis is the most common fungal skin infection, and it is frequently seen in the setting of other concomitant fungal infections, the most common being tinea pedis. Infected nails become a reservoir of fungal organisms that may infect the skin, and vice versa. Early, effective treatment of the nails is necessary for preventing not only permanent structural damage but also the spread and superinfection of the surrounding skin and soft tissue. Moreover, treatment of the skin is important for preventing re-infection of the nails.

New Topical Therapeutic Options in the Management of Superficial Fungal Infections.

Dermatophyte infections of the skin and nails are common in the United States. These infections warrant treatment because they are symptomatic and progressive, and can predispose patients to superinfections. Topical drugs such as luliconazole, naftifine, efinaconazole, and tavaborole are newer options for treating these dermatophyte infections with proven safety, efficacy, and ease of use.

Total Defense + Repair: A Novel Concept in Solar Protection and Skin Rejuvenation.

For more than a century, solar radiation has been known to contribute significantly to the extrinsic aging of skin. Until recently, this was almost exclusively attributed to the photodamage caused by ultraviolet (UV) light. However, a growing body of evidence now indicates that both infrared (IR) and visible light may also contribute to extrinsic skin aging. Infrared radiation, comprised of IR-A, IR-B, and IR-C, accounts for 54.3% of the total solar radiation reaching the skin. Studies have shown that IR radiation is also responsible for skin aging. Thus, IR-A radiation regulates hundreds of genes in skin, with roles in extracellular matrix (ECM) homeostasis regulation, apoptosis, cell growth, and stress responses. IR-B and IR-C radiation are primarily responsible for the increase in skin temperature associated with solar exposure, and are implicated in heat-related skin destruction of collagen and elastin, which is characterized by an increase in the expression of matrix metalloproteinases (MMPs). The contribution of visible light to photoaging is less well understood; however, some preliminary indication associates visible light with the upregulation of MMPs' expression, DNA damage, and keratinocyte proliferation. Interestingly, the common denominator that links skin damage to the different solar wavelengths is the enhanced production of reactive molecule species (RMS) and therewith increased oxidative stress. SkinMedica® Total Defense + Repair (TD+R; SkinMedica Inc., an Allergan company, Irvine, CA) is a "superscreen," which combines broad spectrum UV protection with a unique blend of antioxidants (SOL-IR Advanced Antioxidant Complex™) that provide protection from IR radiation while promoting skin repair. Preclinical studies have indicated that TD+R SPF34 prevents the formation of UV-induced sunburn cells and cyclobutane pyrimidine dimers while preserving or improving the expression of ECM genes. In addition, it prevents IR-A-triggered fragmentation of elastin fibers and expression of MMP-1. Initial clinical studies indicate that TDR+R SPF34 reduces the increase in surface temperature seen with IR radiation. A significant improvement in the appearance of lines and wrinkles was reported as early as week 2 in patients using TDR+R SPF34. In summary, we observed that the unique blend of antioxidants present in TD+R acts in harmony with SPF active ingredients, expanding solar protection beyond UV radiation and counterbalancing the deleterious effects of free radicals on skin cells by promoting endogenous repair.

Therapeutic implications of the circadian clock on skin function.

The human circadian clock ensures that biochemical and physiological processes occur at the optimal time of day. In addition to a central pacemaker in the body, recent evidence suggests that peripheral mammalian tissues also possess autonomous circadian oscillators, which are regulated by genes linked to distinct tissue-specific functions. The skin is situated in a position naturally exposed to diurnal environmental changes. The skin's chronobiological functioning influences skin aging, cell repair and development of skin cancers, as well as optimal timing of drug delivery to the skin. An understanding of circadian skin-related functions and the impact of their disruption allow clinicians to improve therapeutic decision-making and maximize the effectiveness of prescribed treatments.

What is new in fungal pharmacotherapeutics?

Approximately 20-25% of the population worldwide is affected by superficial cutaneous mycoses (SCM). SCM are cutaneous fungal infections with a wide array of systemic and topical treatment options. However, successful therapeutic outcomes are limited by patient non-adherence, medication side effects, potential drug interactions, antifungal resistance and disease recurrence. Advances in formulation technology have allowed for the development of more effective and safer therapies. In this article we will review several new and emerging pharmacotherapeutics for onychomycosis and tinea pedis.

Evaluating and treating the adult female patient with acne.

Acne vulgaris is a common disease of the pilosebacous unit that affects an estimated 40-50 million Americans. Greater than 95% of teenage boys and between 83% and 85% of teenage girls suffer from acne. The condition frequently continues into adulthood. While boys more commonly suffer from acne in the teenage years, greater numbers of women suffer into adulthood. It is unclear if the number of post-adolescent women with acne is rising as compared to the past, or whether women are now seeking out treatment more than in the past.(4) Post-adolescent acne is a significant problem for women. One survey-based United States study found that approximately 50% of women continue to suffer from acne in their twenties, 35% in their thirties, 26% in their forties, and 15% in their fifties. The prevalence of acne was shown to be higher in women than in men in each of these age groups.(7) A similar study from Europe showed that beyond the age of 23, acne is more prevalent in women than men. In their forties and fifties, 5% and 8% of women suffered from acne, respectively. Several other studies have provided similar data, showing that larger numbers of adult women suffer from acne as compared to age matched men. Acne is the number one reason that patients visit a dermatologist. While the mean age at which patients are seen for acne is 24 years old, 10% of visits occur in patients in their mid-thirties and forties. Approximately two thirds of dermatology visits for acne are made by women, and one-third of total acne office visits are made by women over 25 years old. Acne patients suffer from a significant psychological burden, which has been compared to that of patients with systemic diseases like diabetes, asthma, arthritis, or epilepsy. Up to 50% of adolescents with acne experience disturbances to their psyche, including issues with body image, anxiety, depression, poor self-esteem, social impairment, and thoughts of suicide. Moreover, acne treatment is expensive. The average total cost of care related to an acne patient's visit to the dermatologist is estimated to be $689.(14)

Efficacy and safety of tretinoin 0.025%/clindamycin phosphate 1.2% gel in combination with benzoyl peroxide 6% cleansing cloths for the treatment of facial acne vulgaris.

Combination therapy using medications with complementary mechanisms of action is the standard of care in treating acne. We report results of a clinical trial evaluating the use of a fixed-dose tretinoin 0.025%/clindamycin phosphate 1.2% (T/CP) gel in combination with a benzoyl peroxide 6% foaming cloth compared with T/CP alone for facial acne. At week 12, the combination therapy group showed a trend toward greater efficacy compared with T/CP alone. There was a high success rate observed in the study, which may be attributable to the large percentage of adult female acne patients enrolled. Cutaneous adverse events were not statistically different in using combination therapy compared with T/CP alone.

Dermal sensitization, safety, and tolerability of triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel from three clinical trials.

BACKGROUND: Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel. METHODS: Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne. RESULTS: A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: n = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed "moderately irritating") was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel. CONCLUSIONS: The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acne.

Improvements in acne and skin oiliness with tazarotene 0.045% lotion in patients with oily skin.

BACKGROUND: Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. OBJECTIVE: Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. RESULTS: In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p < 0.001, both) and greater treatment success rates versus vehicle (p < 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting 'low/not' oily skin. Tazarotene TEAE rates were similar to the overall population. CONCLUSIONS: Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne.

Optimizing topical combination therapy for the treatment of acne vulgaris.

Given the multifactorial and complex contributors to acne development, combination therapy is standard of care. By addressing multiple pathogenic factors, combination therapy provides a quicker and more efficacious treatment outcome than monotherapy. Topical retinoids normalize follicular keratinocyte differentiation and are anti-inflammatory. Their use is limited by the potential for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects. Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed-dose combination products or two separate medications. BPO has the added benefit of being comedolytic and can minimize the risk for bacterial antibiotic resistance. Like topical retinoids, BPO may cause skin irritation, burning, erythema, and peeling. Managing cutaneous side effects when using multiple products that cause irritation can be a challenge. Careful product selection, dose titration, and patient-directed regimens can help to optimize outcomes. This review presents the latest data on two topical acne products that have demonstrated excellent efficacy and tolerability profiles. In addition, their in vitro profiles suggest the potential for combination use, affording greater dosing flexibility.

Considerations when initiating psoriasis patients on biologic therapy.

Several types of systemic therapies exist to treat psoriasis. These include traditional immunosuppressive agents such as cyclosporine and methotrexate. Oral retinoids such as acitretin may also be appropriate in some patients. The scope of this paper, however, will focus on the use of targeted immunologic therapies, know as biologic agents.

Use of blunt tipped cannulas for soft tissue fillers.

In the US, soft tissue fillers are currently administered using sharp, hypodermic needles. The choice in length and gauge of needle is determined by the injector's preferences, as well as the physical properties of the filler itself. While some adverse events are injector-dependent, others may be due to risks inherent to using sharp needles. The use of new, flexible cannulas with blunt tips may potentially both lower these risks and change the techniques by which fillers are administered in the future.

Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel in the morning in combination with a ceramide containing moisturizer followed by tretinoin 0.05% gel in the evening for the treatment of facial acne vulgaris.

Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.