The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Lee T Zane - One of the best experts on this subject based on the ideXlab platform.
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a novel nonsteroidal topical anti inflammatory phosphodiesterase 4 inhibitor Crisaborole ointment reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults
Pediatrics, 2018Co-Authors: Adelaide A Hebert, Eric L Simpson, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H Hughes, Lee T ZaneAbstract:Background: Atopic dermatitis (AD) is an inflammatory skin disease that presents with intense pruritus and red, inflamed lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, topical anti-inflammatory, phosphodiesterase 4 inhibitor for the treatment of AD. Objective: To evaluate the additional predefined efficacy endpoints on the impact of Crisaborole ointment on pruritus and signs of AD from 2 Phase …
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Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non-steroidal, Phosphodiesterase 4 Inhibitor
Society for Publication of Acta Dermato-Venereologica, 2018Co-Authors: Gil Yosipovitch, Linda F. Gold, Mark G. Lebwohl, Jonathan I. Silverberg, Anna M. Tallman, Lee T ZaneAbstract: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. Patients received Crisaborole or vehicle twice daily for 28 days. Pruritus was graded on a 4-point scale of none (0) to severe (3). Early improvement in pruritus required a score of none (0) or mild (1), with a ≥ 1-grade improvement from baseline on day 6. Significantly more patients experienced early improvement in pruritus with Crisaborole than with vehicle (56.6% vs 39.5%; p
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long term safety of Crisaborole ointment 2 in children and adults with mild to moderate atopic dermatitis
Journal of The American Academy of Dermatology, 2017Co-Authors: Adelaide A Hebert, Lawrence F Eichenfield, Robert S Call, Douglass W Forsha, Joseph F Fowler, Mary Spellman, Linda Stein Gold, Merrie Van Syoc, Lee T ZaneAbstract: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.
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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
Journal of Immunology, 2016Co-Authors: Lee T Zane, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W Forsha, William C ReesAbstract: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’s 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 P = 0.005; 302: 48.5% vs 29.7%, P P
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Crisaborole topical ointment 2 a novel nonsteroidal anti inflammatory topical phosphodiesterase 4 inhibitor reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults with mild to moderate atopic dermatitis
Journal of Immunology, 2016Co-Authors: Lee T Zane, Eric L Simpson, Mark Lebwohl, Adelaide A Hebert, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H HughesAbstract:Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus and eczematous lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, anti-inflammatory, topical, phosphodiesterase 4 inhibitor for the treatment of AD. Here, we present the impact of Crisaborole on pruritus and signs of AD evaluated as supportive efficacy endpoints for 2 Phase 3 studies (301, 302). Patients ≥2 years old with mild-to-moderate AD were enrolled in 2 double-blind, vehicle-controlled, multicenter Phase 3 studies of identical design. Patients were randomized 2:1 to receive Crisaborole or vehicle twice daily for 28 days. Supportive efficacy endpoints examined severity of pruritus (measured twice daily) and signs of AD (measured weekly) on a 4-point scale (None [0] to Severe [3]). Success was defined for pruritus or each sign or symptom of AD as achievement of None (0) or Mild (1) with ≥1-grade improvement from baseline. Improvement in pruritus was achieved sooner in Crisaborole-treated patients than vehicle-treated patients (pooled data: median, 1.37 vs 1.70 days; P = 0.001). A greater proportion of Crisaborole-treated patients achieved success for all clinical signs of AD by Day 29 (301, 302; erythema: 62.8% vs 46.1%; 54.9% vs 33.9%; induration/papulation: 57.7% vs 54.8%; −51.9% vs 40.2%; exudation: 41.0% vs 33.3%; 38.1% vs 27.2%; excoriation: 63.0% vs 51.8%; 57.2% vs 44.2%; lichenification: 51.7% vs 46.5%; 51.4% vs 35.3%). In 2 large Phase 3 studies, Crisaborole demonstrated early relief of pruritus and showed improvement in all measured signs of AD. Crisaborole Topical Ointment, 2%, may represent a safe and efficacious treatment for patients ≥2 years with mild-to-moderate AD.
Lawrence F Eichenfield - One of the best experts on this subject based on the ideXlab platform.
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a novel nonsteroidal topical anti inflammatory phosphodiesterase 4 inhibitor Crisaborole ointment reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults
Pediatrics, 2018Co-Authors: Adelaide A Hebert, Eric L Simpson, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H Hughes, Lee T ZaneAbstract:Background: Atopic dermatitis (AD) is an inflammatory skin disease that presents with intense pruritus and red, inflamed lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, topical anti-inflammatory, phosphodiesterase 4 inhibitor for the treatment of AD. Objective: To evaluate the additional predefined efficacy endpoints on the impact of Crisaborole ointment on pruritus and signs of AD from 2 Phase …
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long term safety of Crisaborole ointment 2 in children and adults with mild to moderate atopic dermatitis
Journal of The American Academy of Dermatology, 2017Co-Authors: Adelaide A Hebert, Lawrence F Eichenfield, Robert S Call, Douglass W Forsha, Joseph F Fowler, Mary Spellman, Linda Stein Gold, Merrie Van Syoc, Lee T ZaneAbstract: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.
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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
Journal of The American Academy of Dermatology, 2016Co-Authors: Amy S Paller, Mark Lebwohl, Lawrence F Eichenfield, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W ForshaAbstract: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. 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 P = .005; 48.5% vs 29.7%, P 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.
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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
Journal of Immunology, 2016Co-Authors: Lee T Zane, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W Forsha, William C ReesAbstract: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’s 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 P = 0.005; 302: 48.5% vs 29.7%, P P
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Crisaborole topical ointment 2 a novel nonsteroidal anti inflammatory topical phosphodiesterase 4 inhibitor reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults with mild to moderate atopic dermatitis
Journal of Immunology, 2016Co-Authors: Lee T Zane, Eric L Simpson, Mark Lebwohl, Adelaide A Hebert, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H HughesAbstract:Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus and eczematous lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, anti-inflammatory, topical, phosphodiesterase 4 inhibitor for the treatment of AD. Here, we present the impact of Crisaborole on pruritus and signs of AD evaluated as supportive efficacy endpoints for 2 Phase 3 studies (301, 302). Patients ≥2 years old with mild-to-moderate AD were enrolled in 2 double-blind, vehicle-controlled, multicenter Phase 3 studies of identical design. Patients were randomized 2:1 to receive Crisaborole or vehicle twice daily for 28 days. Supportive efficacy endpoints examined severity of pruritus (measured twice daily) and signs of AD (measured weekly) on a 4-point scale (None [0] to Severe [3]). Success was defined for pruritus or each sign or symptom of AD as achievement of None (0) or Mild (1) with ≥1-grade improvement from baseline. Improvement in pruritus was achieved sooner in Crisaborole-treated patients than vehicle-treated patients (pooled data: median, 1.37 vs 1.70 days; P = 0.001). A greater proportion of Crisaborole-treated patients achieved success for all clinical signs of AD by Day 29 (301, 302; erythema: 62.8% vs 46.1%; 54.9% vs 33.9%; induration/papulation: 57.7% vs 54.8%; −51.9% vs 40.2%; exudation: 41.0% vs 33.3%; 38.1% vs 27.2%; excoriation: 63.0% vs 51.8%; 57.2% vs 44.2%; lichenification: 51.7% vs 46.5%; 51.4% vs 35.3%). In 2 large Phase 3 studies, Crisaborole demonstrated early relief of pruritus and showed improvement in all measured signs of AD. Crisaborole Topical Ointment, 2%, may represent a safe and efficacious treatment for patients ≥2 years with mild-to-moderate AD.
Amy S Paller - One of the best experts on this subject based on the ideXlab platform.
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a novel nonsteroidal topical anti inflammatory phosphodiesterase 4 inhibitor Crisaborole ointment reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults
Pediatrics, 2018Co-Authors: Adelaide A Hebert, Eric L Simpson, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H Hughes, Lee T ZaneAbstract:Background: Atopic dermatitis (AD) is an inflammatory skin disease that presents with intense pruritus and red, inflamed lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, topical anti-inflammatory, phosphodiesterase 4 inhibitor for the treatment of AD. Objective: To evaluate the additional predefined efficacy endpoints on the impact of Crisaborole ointment on pruritus and signs of AD from 2 Phase …
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phosphodiesterase 4 inhibitors
Journal of The American Academy of Dermatology, 2017Co-Authors: Rema Zebda, Amy S PallerAbstract:Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration–approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety.
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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
Journal of The American Academy of Dermatology, 2016Co-Authors: Amy S Paller, Mark Lebwohl, Lawrence F Eichenfield, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W ForshaAbstract: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. 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 P = .005; 48.5% vs 29.7%, P 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.
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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
Journal of Immunology, 2016Co-Authors: Lee T Zane, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W Forsha, William C ReesAbstract: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’s 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 P = 0.005; 302: 48.5% vs 29.7%, P P
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Crisaborole topical ointment 2 a novel nonsteroidal anti inflammatory topical phosphodiesterase 4 inhibitor reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults with mild to moderate atopic dermatitis
Journal of Immunology, 2016Co-Authors: Lee T Zane, Eric L Simpson, Mark Lebwohl, Adelaide A Hebert, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H HughesAbstract:Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus and eczematous lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, anti-inflammatory, topical, phosphodiesterase 4 inhibitor for the treatment of AD. Here, we present the impact of Crisaborole on pruritus and signs of AD evaluated as supportive efficacy endpoints for 2 Phase 3 studies (301, 302). Patients ≥2 years old with mild-to-moderate AD were enrolled in 2 double-blind, vehicle-controlled, multicenter Phase 3 studies of identical design. Patients were randomized 2:1 to receive Crisaborole or vehicle twice daily for 28 days. Supportive efficacy endpoints examined severity of pruritus (measured twice daily) and signs of AD (measured weekly) on a 4-point scale (None [0] to Severe [3]). Success was defined for pruritus or each sign or symptom of AD as achievement of None (0) or Mild (1) with ≥1-grade improvement from baseline. Improvement in pruritus was achieved sooner in Crisaborole-treated patients than vehicle-treated patients (pooled data: median, 1.37 vs 1.70 days; P = 0.001). A greater proportion of Crisaborole-treated patients achieved success for all clinical signs of AD by Day 29 (301, 302; erythema: 62.8% vs 46.1%; 54.9% vs 33.9%; induration/papulation: 57.7% vs 54.8%; −51.9% vs 40.2%; exudation: 41.0% vs 33.3%; 38.1% vs 27.2%; excoriation: 63.0% vs 51.8%; 57.2% vs 44.2%; lichenification: 51.7% vs 46.5%; 51.4% vs 35.3%). In 2 large Phase 3 studies, Crisaborole demonstrated early relief of pruritus and showed improvement in all measured signs of AD. Crisaborole Topical Ointment, 2%, may represent a safe and efficacious treatment for patients ≥2 years with mild-to-moderate AD.
Wynnis L Tom - One of the best experts on this subject based on the ideXlab platform.
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a novel nonsteroidal topical anti inflammatory phosphodiesterase 4 inhibitor Crisaborole ointment reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults
Pediatrics, 2018Co-Authors: Adelaide A Hebert, Eric L Simpson, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H Hughes, Lee T ZaneAbstract:Background: Atopic dermatitis (AD) is an inflammatory skin disease that presents with intense pruritus and red, inflamed lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, topical anti-inflammatory, phosphodiesterase 4 inhibitor for the treatment of AD. Objective: To evaluate the additional predefined efficacy endpoints on the impact of Crisaborole ointment on pruritus and signs of AD from 2 Phase …
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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
Journal of The American Academy of Dermatology, 2016Co-Authors: Amy S Paller, Mark Lebwohl, Lawrence F Eichenfield, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W ForshaAbstract: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. 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 P = .005; 48.5% vs 29.7%, P 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.
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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
Journal of Immunology, 2016Co-Authors: Lee T Zane, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W Forsha, William C ReesAbstract: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’s 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 P = 0.005; 302: 48.5% vs 29.7%, P P
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Crisaborole topical ointment 2 a novel nonsteroidal anti inflammatory topical phosphodiesterase 4 inhibitor reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults with mild to moderate atopic dermatitis
Journal of Immunology, 2016Co-Authors: Lee T Zane, Eric L Simpson, Mark Lebwohl, Adelaide A Hebert, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H HughesAbstract:Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus and eczematous lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, anti-inflammatory, topical, phosphodiesterase 4 inhibitor for the treatment of AD. Here, we present the impact of Crisaborole on pruritus and signs of AD evaluated as supportive efficacy endpoints for 2 Phase 3 studies (301, 302). Patients ≥2 years old with mild-to-moderate AD were enrolled in 2 double-blind, vehicle-controlled, multicenter Phase 3 studies of identical design. Patients were randomized 2:1 to receive Crisaborole or vehicle twice daily for 28 days. Supportive efficacy endpoints examined severity of pruritus (measured twice daily) and signs of AD (measured weekly) on a 4-point scale (None [0] to Severe [3]). Success was defined for pruritus or each sign or symptom of AD as achievement of None (0) or Mild (1) with ≥1-grade improvement from baseline. Improvement in pruritus was achieved sooner in Crisaborole-treated patients than vehicle-treated patients (pooled data: median, 1.37 vs 1.70 days; P = 0.001). A greater proportion of Crisaborole-treated patients achieved success for all clinical signs of AD by Day 29 (301, 302; erythema: 62.8% vs 46.1%; 54.9% vs 33.9%; induration/papulation: 57.7% vs 54.8%; −51.9% vs 40.2%; exudation: 41.0% vs 33.3%; 38.1% vs 27.2%; excoriation: 63.0% vs 51.8%; 57.2% vs 44.2%; lichenification: 51.7% vs 46.5%; 51.4% vs 35.3%). In 2 large Phase 3 studies, Crisaborole demonstrated early relief of pruritus and showed improvement in all measured signs of AD. Crisaborole Topical Ointment, 2%, may represent a safe and efficacious treatment for patients ≥2 years with mild-to-moderate AD.
Mark Lebwohl - One of the best experts on this subject based on the ideXlab platform.
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a novel nonsteroidal topical anti inflammatory phosphodiesterase 4 inhibitor Crisaborole ointment reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults
Pediatrics, 2018Co-Authors: Adelaide A Hebert, Eric L Simpson, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H Hughes, Lee T ZaneAbstract:Background: Atopic dermatitis (AD) is an inflammatory skin disease that presents with intense pruritus and red, inflamed lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, topical anti-inflammatory, phosphodiesterase 4 inhibitor for the treatment of AD. Objective: To evaluate the additional predefined efficacy endpoints on the impact of Crisaborole ointment on pruritus and signs of AD from 2 Phase …
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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
Journal of The American Academy of Dermatology, 2016Co-Authors: Amy S Paller, Mark Lebwohl, Lawrence F Eichenfield, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W ForshaAbstract: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. 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 P = .005; 48.5% vs 29.7%, P 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.
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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
Journal of Immunology, 2016Co-Authors: Lee T Zane, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W Forsha, William C ReesAbstract: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’s 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 P = 0.005; 302: 48.5% vs 29.7%, P P
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Crisaborole topical ointment 2 a novel nonsteroidal anti inflammatory topical phosphodiesterase 4 inhibitor reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults with mild to moderate atopic dermatitis
Journal of Immunology, 2016Co-Authors: Lee T Zane, Eric L Simpson, Mark Lebwohl, Adelaide A Hebert, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Matilda H HughesAbstract:Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus and eczematous lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, anti-inflammatory, topical, phosphodiesterase 4 inhibitor for the treatment of AD. Here, we present the impact of Crisaborole on pruritus and signs of AD evaluated as supportive efficacy endpoints for 2 Phase 3 studies (301, 302). Patients ≥2 years old with mild-to-moderate AD were enrolled in 2 double-blind, vehicle-controlled, multicenter Phase 3 studies of identical design. Patients were randomized 2:1 to receive Crisaborole or vehicle twice daily for 28 days. Supportive efficacy endpoints examined severity of pruritus (measured twice daily) and signs of AD (measured weekly) on a 4-point scale (None [0] to Severe [3]). Success was defined for pruritus or each sign or symptom of AD as achievement of None (0) or Mild (1) with ≥1-grade improvement from baseline. Improvement in pruritus was achieved sooner in Crisaborole-treated patients than vehicle-treated patients (pooled data: median, 1.37 vs 1.70 days; P = 0.001). A greater proportion of Crisaborole-treated patients achieved success for all clinical signs of AD by Day 29 (301, 302; erythema: 62.8% vs 46.1%; 54.9% vs 33.9%; induration/papulation: 57.7% vs 54.8%; −51.9% vs 40.2%; exudation: 41.0% vs 33.3%; 38.1% vs 27.2%; excoriation: 63.0% vs 51.8%; 57.2% vs 44.2%; lichenification: 51.7% vs 46.5%; 51.4% vs 35.3%). In 2 large Phase 3 studies, Crisaborole demonstrated early relief of pruritus and showed improvement in all measured signs of AD. Crisaborole Topical Ointment, 2%, may represent a safe and efficacious treatment for patients ≥2 years with mild-to-moderate AD.
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Crisaborole topical ointment 2 a nonsteroidal topical anti inflammatory phosphodiesterase 4 inhibitor in clinical development for the treatment of atopic dermatitis
Journal of Drugs in Dermatology, 2016Co-Authors: Kurt Jarnagin, Lee T Zane, Sanjay Chanda, Dina Coronado, E Guttmanyassky, Mark LebwohlAbstract: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. The use of boron chemistry enabled synthesis of a low-molecular-weight compound (251 daltons), thereby facilitating effective penetration of Crisaborole through human skin. In vitro experiments showed that Crisaborole inhibits cytokine production from peripheral blood mononuclear cells in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids. Crisaborole also displayed topical anti-inflammatory activity in a skin inflammation model. Once Crisaborole reaches systemic circulation after topical application, it is metabolized to inactive metabolites. This limits systemic exposure to Crisaborole and systemic PDE4 inhibition. In phase 1 and 2 clinical studies, Crisaborole ointment, 2% was generally well tolerated and improved AD disease severity scores, pruritus, and all other AD signs and symptoms. Two large, randomized, controlled, phase 3, pivotal clinical trials assessing the efficacy and safety of Crisaborole topical ointment, 2% in children, adolescents, and adults with mild to moderate AD were recently completed with positive results.