Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies
February 2016 | Volume 15 | Issue 2 | Original Article | 172 | Copyright © 2016
Zoe Diana Draelos MD,a Linda F. Stein Gold MD,b Dedee F. Murrell MD,c Matilda H. Hughes CCRA,d and Lee T. Zane MDd
aDermatology Consulting Services, High Point, NC
bHenry Ford Medical Center, Detroit, MI
cSt. George Hospital, University of New South Wales, Sydney, Australia
dAnacor Pharmaceuticals, Inc., Palo Alto, CA
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). Pooled data from studies 1 and 2 included whole body assessments; studies 3 and 4 included target lesion assessments. Pruritus severity was evaluated using a 4-point rating scale (0=none to 3=severe). Efficacy assessments included percent change from baseline in pruritus severity scores at days 8 (first pooled assessment), 15, 22, and 29 (whole body assessments) or days 15 (first pooled assessment), 22, and 29 (target lesions). Paired t-tests comparing change from baseline against zero were used to calculate P values. Categorical shifts in pruritus severity were also assessed (no to mild pruritus, 0–1.5; moderate to severe pruritus, 2–3).
RESULTS: In the pooled analysis of studies 1 and 2 (N=57), the percent change from baseline in pruritus severity scores were 63.0% and 64.9% at days 8 and 29, respectively (P<0.001 for each). Similar results were observed in the pooled analysis of studies 3 and 4 (N=67). In both analyses, most patients had mild to no pruritus from the first time point assessed through the remainder of treatment.
CONCLUSIONS: Treatment with crisaborole topical ointment, 2% resulted in statistically significant reductions in pruritus severity at the first time point evaluated in both analyses. These findings provide preliminary evidence of the antipruritic activity of crisaborole topical ointment, 2%.
J Drugs Dermatol. 2016;15(2):172-176.
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Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by intense pruritus.1,2 Quality of life can be substantially reduced for patients with AD and their caregivers, as pruritus can cause disruption of sleep and concentration as well as social stigmatization.3-6 In addition, sleep disruption in children with AD has been associated with deficits in neurocognitive function.7 However, early and effective treatment may reduce itching, prevent sleep disturbances, and ultimately improve quality of life for patients with AD and their caregivers.
Current treatment guidelines recommend nonpharmacologic moisturizers and topical pharmacotherapies for the effective management of patients with AD.8 Although topical corticosteroids and calcineurin inhibitors are often recommended, many patients and caregivers have concerns about the long-term safety of these therapies.8,9 Short-term, intermittent use of oral, sedating antihistamines may reduce both sleep impairments and itch in patients with pruritus, but is not recommended as part of treatment for patients with AD.10 In addition, the topical pharmacologic treatments currently available to patients with mild to moderate AD do not permit long-term use due to safety concerns.8
Crisaborole topical ointment, 2% (crisaborole [formerly AN2728]; Anacor Pharmaceuticals, Inc., Palo Alto, CA), is a first-in-class, boron-based, small-molecule phosphodiesterase-4 (PDE4) inhibitor in clinical development for mild to moderate AD.11 In phase 1 and 2 clinical studies of patients with AD, treatment with crisaborole topical ointment, 2% improved Investigator Static Global Assessment (ISGA) and Atopic Dermatitis Severity Index (ADSI) scores, pruritus, and all other AD