Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families.

Introduction: The impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov ).

Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non-steroidal, Phosphodiesterase 4 Inhibitor.

Pruritus occurs in all patients with atopic dermatitis and requires quick relief to reduce disease exacerbation and improve quality of life. Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment for early relief of pruritus in patients with mild to moderate atopic dermatitis from 2 phase III studies.

Clinical trial designs for topical antifungal treatments of onychomycosis and implications on clinical practice.

There currently are 3 topical agents approved by the US Food and Drug Administration (FDA) to treat onychomycosis: tavaborole, efinaconazole, and ciclopirox. The phase 3 clinical trial designs for these treatments and their notable differences make it difficult for clinicians to interpret the data into clinical practice. For example, the primary end point predominantly used to assess efficacy in all the trials is complete cure, defined as no involvement of the nail plus mycologic cure; also, a notable number of patients fail to achieve a complete cure despite clear improvement in the nail.

Tavaborole in Difficult-to-Treat Onychomycosis Cases: A Post-hoc Assessment of Phase III Subjects.

Toenail onychomycosis is a chronic fungal infection that often requires prolonged treatment in order to effectively manage pathogenic organisms and obtain a clear nail. Traditionally, certain clinical features of onychomycosis, including the presence of substantial lateral disease, focal fungal masses, yellow/brown streaks, and extensive nail involvement (ie, >50%), indicate a poor treatment prognosis and have proven difficult-to-treat with oral or traditional topical therapies. Owing to the novel features of topical tavaborole, we sought to understand the potential utility of tavaborole in difficult-to-treat onychomycosis.

Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.

Background: Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease.

Objective: To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302).

Methods: Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated.

Evaluation of the efficacy and safety of tavaborole topical solution, 5%, in the treatment of onychomycosis of the toenail in adults: a pooled analysis of an 8-week, post-study follow-up from two randomized phase 3 studies.

Purpose: The role of topical antifungal agents in the long-term management of toenail onychomycosis is not well established. The current study evaluated durability of clinical benefit of tavaborole topical solution, 5%, for the treatment of toenail onychomycosis.

Methods: We conducted a pooled analysis of 8-week, post-study follow-up (PSFU) data from two phase 3, randomized controlled trials in a subset of patients who experienced complete or almost clear nail (CN) at the end of treatment (week 52); 48 weeks of treatment with once-daily tavaborole compared with placebo in adults with distal subungual onychomycosis was evaluated at week 60.

Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults.

Background: Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks.

Objective: We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792).

Methods: Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days.

Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers.

Background: Inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis often present in sensitive and thin-skinned areas that are at higher risk for topical treatment-related skin irritation (e.g., burning, stinging).

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open-Label, Maximal-Use Systemic Exposure Study.

Background: Phosphodiesterase-4 (PDE4) is a promising target in atopic dermatitis (AD) treatment. The pharmacokinetics (PK), safety, and efficacy of crisaborole topical ointment, 2% (formerly AN2728) (Anacor Pharmaceuticals, Palo Alto, CA), a boron-based benzoxaborole PDE4 inhibitor, were evaluated in children with mild to moderate AD.

Methods: This phase 1b, open-label, maximal-use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg/cm(2) ) for 28 days enrolled patients ages 2 to 17 years with extensive AD involving 25% or more or 35% or more treatable body surface area, depending on age.

Antifungal agents for onychomycosis: new treatment strategies to improve safety.

Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection.

Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis.

Crisaborole topical ointment, 2% (formerly known as AN2728) is a benzoxaborole, nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor investigational compound that recently completed phase 3 studies for the treatment of mild to moderate atopic dermatitis (AD). The unique configuration of boron within the crisaborole molecule enables selective targeting and inhibition of PDE4, an enzyme that converts the intracellular second messenger 3'5'-cyclic adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate (AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole controls inflammation.

Clinician vs Self-ratings of Hirsutism in Patients With Polycystic Ovarian Syndrome: Associations With Quality of Life and Depression.

Importance: Qualitative evidence suggests that hirsutism inflicts significant negative impacts on quality of life and may be associated with depression. Quantitative research is essential to determine best practices in caring for hirsute patients.

Objective: To quantify quality-of-life impact of hirsutism and evaluate how the degree of hirsutism (as assessed by patients and clinicians) is associated with quality of life and depressive symptoms.

Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies.

Background: Two post hoc analyses assessed the antipruritic activity of crisaborole topical ointment, 2% (crisaborole; Anacor Pharmaceuticals, Inc., Palo Alto, CA), a first-in-class boron-based phosphodiesterase-4 inhibitor in development for treatment of mild to moderate atopic dermatitis (AD).

Methods: Two pooled analyses included data from 4 studies evaluating crisaborole in AD (study 1, phase 1b, systemic exposure, safety, and pharmacokinetics [PK] under maximal-use conditions in children and adolescents; study 2, phase 2a, safety and PK in adolescents; study 3, phase 2a, efficacy and safety in adults; study 4, phase 2, efficacy and safety in adolescents).

Evaluation of the Appearance of Nail Polish Following Daily Treatment of Ex Vivo Human Fingernails With Topical Solutions of Tavaborole or Efinaconazole.

Introduction: Patients with onychomycosis may mask infected nails with polish. Tavaborole topical solution, 5% is a boron-based, small-molecule pharmaceutical approved for the treatment of toenail onychomycosis caused by Trichophyton rubrum and Trichophyton mentagrophytes; efinaconazole topical solution, 10% is approved for the same indication. Nail polish appearance after application of tavaborole (dropper) or efinaconazole (brush); respective applicator appearance; presence of color transfer from respective applicators; and color transfer to remaining solutions after dosing of polished nails were evaluated.

Cutaneous Findings and Systemic Associations in Women With Polycystic Ovary Syndrome.

Importance: Understanding of the associations among cutaneous findings, systemic abnormalities, and fulfillment of the diagnostic criteria in women suspected of having polycystic ovary syndrome (PCOS) is incomplete.

Objective: To identify cutaneous and systemic features of PCOS that help distinguish women who do and do not meet the diagnostic criteria.

Design, Setting, And Participants: Retrospective cross-sectional study of a racially diverse referred sample of women seen at the University of California, San Francisco, Polycystic Ovary Syndrome Multidisciplinary Clinic over a 6-year period between May 18, 2006, and October 25, 2012.

A Phase 2, Randomized, Controlled, Dose-Ranging Study Evaluating Crisaborole Topical Ointment, 0.5% and 2% in Adolescents With Mild to Moderate Atopic Dermatitis.

Background: Crisaborole is a novel, boron-based, small-molecule, topical phosphodiesterase-4 inhibitor in development for the treatment of patients with mild to moderate atopic dermatitis (AD).

Methods: In this multicenter, randomized, double-blind, dose-ranging, phase 2 study, adolescent patients 12 to 17 years of age with mild to moderate AD and 2 distinct target AD lesions were randomized to once-daily (QD) or twice-daily (BID) treatment with crisaborole topical ointment. For each patient, 2 target lesions were randomized to receive 29 days of treatment with 0.

Crisaborole Topical Ointment, 2% in Adults With Atopic Dermatitis: A Phase 2a, Vehicle-Controlled, Proof-of-Concept Study.

Background: A novel approach for treating atopic dermatitis (AD) is the inhibition of phosphodiesterase 4 (PDE4), an enzyme involved in the proinflammatory cascade. Crisaborole topical ointment, 2% is a novel, boron-based small-molecule PDE4 inhibitor with anti-inflammatory properties. The objective of this proof-of-concept study was to assess the efficacy and safety of crisaborole topical ointment, 2% in adults with mild to moderate AD.

In Vitro Nail Penetration of Tavaborole Topical Solution, 5%, Through Nail Polish on Ex Vivo Human Fingernails.

Background: Onychomycosis is a common infection of the toenails that causes nail thickening and discoloration. The physical appearance of the infected nail can diminish self-image and negatively impact quality of life. Patients may use nail polish to mask the appearance of infected nails.

In Vitro Nail Penetration and Antifungal Activity of Tavaborole, a Boron-Based Pharmaceutical.

An effective topical antifungal medication must penetrate through the nail plate at sufficient concentrations to eradicate the fungal infection. Tavaborole topical solution, 5% is a novel boron-based pharmaceutical approved for the treatment of toenail onychomycosis due to Trichophyton rubrum or T mentagrophytes. Four in vitro studies assessed the antifungal activity and nail penetration of tavaborole.

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies.

Background: Onychomycosis, a fungal nail infection, can impact quality of life.

Objective: We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis.

Methods: In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks.

The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis.

Objective: To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes.

Methods: One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.

Age-related differences in the reproductive and metabolic implications of polycystic ovarian syndrome: findings in an obese, United States population.

The objective of this study was to explore age-related differences in the reproductive and metabolic manifestations of polycystic ovarian syndrome (PCOS). Using a prospective cross-sectional design, we compared metabolic and reproductive findings in women attending a multidisciplinary clinic for PCOS, stratified across the following age groups: 18-25 (n = 71), 26-35 (n = 129), and 36-45 (n = 29). The study included primarily overweight and obese women, with a mean BMI of 31.

Comparative efficacy of nonpurpuragenic pulsed dye laser and intense pulsed light for erythematotelangiectatic rosacea.

Background: Erythematotelangiectatic (ET) rosacea is commonly treated with a variety of laser and light-based systems. Although many have been used successfully, there are a limited number of comparative efficacy studies.

Objective: To compare nonpurpuragenic pulsed dye laser (PDL) with intense pulsed light (IPL) treatment in the ability to reduce erythema, telangiectasia, and symptoms in patients with moderate facial ET rosacea.

A community-based study of acne-related health preferences in adolescents.

Objective: To examine preferences for acne-related outcomes in adolescents.

Design: Community-based, cross-sectional survey study.

Setting: Four public high schools in San Francisco, California.