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. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed. RESULTS: During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs. LIMITATIONS: Long-term efficacy was not analyzed. CONCLUSION: Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD

Long-term safety of crisaborole ointment in children, adolescents, and adults with mild to moderate atopic dermatitis

Introduction: Atopic dermatitis (AD), a chronic inflammatory skin disease, affects children, adolescents, and adults, often requiring long‐term topical treatment. Two 28‐day, pivotal Phase 3 studies demonstrated that crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 inhibitor, improved disease severity in patients ≥2 years old with mild to moderate AD. To evaluate the long‐term safety of crisaborole ointment across 3 key patient groups (children, adolescents, and adults), patients from the pivotal trials were assessed in a Phase 3, open‐label extension study. Methods: After completing a 28‐day Phase 3 pivotal study (AD‐301, AD‐302), eligible patients who opted to continue treatment (N = 517) were enrolled in a multicenter, open‐label, 48‐week safety study (AD‐303). AD severity was assessed every 4 weeks and treated as needed (Investigator\u27s Static Global Assessment ≥2 [mild]) with 4‐week cycles of crisaborole. Treatment‐emergent adverse events (TEAEs) were analyzed by age group for children (2–11 years), adolescents (12–17 years), and adults (≥18 years). Results: During the pivotal studies and extension study, the proportion of patients reporting ≥1 TEAE was similar for children (67.9%) and adolescents (65.1%) and was lower in adults (50.8%). The rate of treatment‐related TEAEs was similar for children (10.4%), adolescents (10.3%), and adults (9.5%). The most frequently reported treatment‐related TEAE by group was atopic dermatitis by children (3.2%), application site pain by adolescents (3.4%), and atopic dermatitis by adults (4.8%). During the extension study, 4 serious AEs were reported in children (infections and infestations: n = 2; nervous system disorders: n = 1; respiratory, thoracic, and mediastinal disorders: n = 1), and 3 were reported in adolescents (immune system disorders: n = 1; psychiatric disorders: n = 2); none were considered related to treatment. No serious AEs were reported in adults. Cutaneous adverse reactions such as application site atrophy and telangiectasia were not reported in any age group. Conclusions: In patients with mild to moderate AD, the long‐term safety profile of crisaborole ointment was similar for children and adolescents; lower rates of AEs and serious AEs were observed in adults

Long-term safety of Crisaborole Topical Ointment, 2%, in children and adults with mild-to-moderate atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires long-termtopical treatment. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Inc., Palo Alto, CA), a novel nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor, is currently being investigated for the treatment of AD. Herein we present the long-term safety results of patients ≥2 years of age with mild-to-moderate AD. A multicenter, open-label, long-term, 48-week, extension safety study was conducted inpatients (N = 517) who opted to continue treatment after completing a 28-day Phase 3 pivotal study. Patients were assessed for AD severity every 4 weeks and treated with 4-week cycles of crisaborole as needed (Investigator\u27s Static Global Assessment ≥2 [Mild]). During the open-label extension and the pivotal studies, 65% of patients reported at least 1 treatment-emergent adverse event (TEAE), most of which were mild (51.2%) or moderate (44.6%) in severity and considered unrelated to treatment (93.1%). Treatment-related AEs occurred in 10.2% of patients; the most frequently reported events were atopic dermatitis(3.1%), application site pain (burning/stinging, 2.3%), and application site infection (1.2%). None of the 7 treatment-emergent serious AEs that occurred in the extension study were considered treatment related. During the long-term study, only 9 patients (1.7%) discontinued the study because of TEAEs. No cutaneous adverse reactions such as application site atrophy, telangiectasia, or hypopigmentation were reported. The safetyprofile of crisaborole was similar across age groups. Crisaborole Topical Ointment, 2%, has a favorable safety profile for the long-term treatment of patients with AD

Two phase 3 study results of children and adults with mild-to-moderate atopic dermatitis treated with Crisaborole Topical Ointment, 2%, a novel, nonsteroidal, topical, anti-inflammatory, phosphodiesterase 4 inhibitor

Up to 90% of children and adults with atopic dermatitis (AD), a chronic inflammatory skin disease, present with mild-to-moderate disease. Crisaborole Topical Ointment, 2%, is a novel, nonsteroidal, topical, anti-inflammatory, phosphodiesterase 4 inhibitor being studied for the treatment of AD. The efficacy and safety of crisaborole was assessed in 2 identically designed, multicenter, vehicle-controlled, double-blind Phase 3 studies (301 and 302) that enrolled patients ≥2 years old with mild-to-moderate AD affecting ≥5% of body surface area (BSA). Patients were randomized 2:1 to receive crisaborole or vehicle twice daily and evaluated on Days 8, 15, 22, and 29. The primary endpoint defined success in the Investigator\u27s Static Global Assessment (ISGA) as “almost clear/1” or “clear/0” with ≥2-grade improvement from baseline at Day 29. Secondary endpoints analyzed the time to success and the percentage of patients achieving “almost clear/1” or “clear/0” on ISGA. At Day 29, more crisaborole-treated patients achieved ISGA success than vehicle (301: 32.8% vs 25.4%, P = 0.038; 302: 31.4% vs 18.0%, P \u3c 0.001), with a greater percentage of “almost clear/1” or “clear/0” ISGA scores (301: 51.7% vs 40.6%, P = 0.005; 302: 48.5% vs 29.7%, P \u3c 0.001). Success in ISGA scores was achieved earlier with crisaborole than vehicle (P \u3c 0.001). Treatment-related adverse events (AEs) were usually mild and included upper respiratory tract infection (pooled data, crisaborole vs vehicle: 3.0% vs 3.0%) and application site pain (4.4% vs 1.2%). AE-related discontinuation rates were low for both groups (1.2%). 2 large Phase 3 studies demonstrated crisaborole may represent a novel, safe, and efficacious treatment for patients with mild-to-moderate AD

Efficacy and Safety of Crisaborole Topical Ointment, 2%, a Novel, Nonsteroidal, Topical, Anti-Inflammatory, Phosphodiesterase Inhibitor in 2 Phase 3 Studies in Children and Adults with Mild-to-Moderate Atopic Dermatitis

Rationale Phosphodiesterase 4 (PDE4) enzyme is overexpressed in inflammatory cells of patients with atopic dermatitis (AD); this leads to disease exacerbation. Here, we present safety and efficacy from 2 multicenter, double-blind, vehicle-controlled phase 3 studies of identical design in patients with mild-to-moderate AD (NCT02118766 and NCT02118792) treated with the novel, nonsteroidal, topical, anti-inflammatory investigational PDE4 inhibitor Crisaborole Topical Ointment, 2%. Methods Patients ≥2 years old with mild-to-moderate AD were randomized 2:1 to receive crisaborole or vehicle twice daily with evaluation on Days 8, 15, 22, and 29. Primary and secondary efficacy endpoints analyzed AD disease severity with the Investigator’s Static Global Assessment (ISGA). Supportive efficacy endpoints examined time to improvement in pruritus, severity of pruritus, and signs of AD. Results Studies 1 and 2 enrolled 503:256 and 513:250 crisaborole/vehicle patients, respectively. At Day 29, more crisaborole-treated patients achieved ISGA success than those treated with vehicle (study 1: 32.8% vs 25.4%, P=0.038; study 2: 31.4% vs 18.0%, PP=0.005; study 2: 48.5% vs 29.7%, PP Conclusions Two Phase 3 studies demonstrate that Crisaborole Topical Ointment, 2%, represents a novel, safe, and efficacious treatment for children and adults with mild-to-moderate AD

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\u27s Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus. RESULTS: More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P \u3c .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P \u3c .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity. LIMITATIONS: Short study duration was a limitation. CONCLUSIONS: Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD