Key clinical-trial evidence for crisaborole

Introduction

In December 2016, the US Food and Drug Administration (FDA) approved 2% crisaborole topical ointment (EUCRISA^™, Anacor Pharmaceuticals, California, USA) to treat mild to moderate atopic dermatitis in patients 2 years of age and older.

The approval of crisaborole was based on results of two large, identical, multicenter, randomised, double-blind, parallel-group, vehicle-controlled (non-medicated ointment) trials (Trials 1 and 2) that treated 1522 patients aged 2–79 years with mild to moderate atopic dermatitis.

Crisaborole is the first and only non-steroidal topical monotherapy for atopic dermatitis that inhibits the phosphodiesterase-4 (PDE-4) enzyme in the skin.

Overactive PDE-4 has been shown to contribute to the signs and symptoms of atopic dermatitis.

Major trials supporting clinical efficacy of crisaborole

• In two phase III studies, crisaborole ointment improved disease severity and pruritus with a favorable safety profile in patients with mild to moderate atopic dermatitis.
• Two multicentre, randomised, double-blind, parallel-group, vehicle-controlled trials (Trials 1 and 2) treated a total of 1522 subjects 2–79 years of age (86.3% of subjects were 2–17 years of age) with a 5–95% treatable body surface area.
• At baseline, 38.5% of the subjects had an Investigator’s Static Global Assessment [ISGA] score of 2 (mild), and 61.5% had an ISGA score of 3 (moderate), in the overall assessment of atopic dermatitis (erythema, induration/papulation, and oozing/crusting) on a severity scale of 0 to 4.
• Subjects were randomized 2:1 to receive crisaborole or vehicle.
• Patients were instructed to apply a thin layer of study drug to cover each lesion twice daily throughout the 28-day study to all affected areas at baseline.
• The scalp was excluded from treatment to avoid potential patient dissatisfaction with ointment application to scalp hair.
• Patients were reviewed at scheduled weekly in-clinic visits (days 8, 15, and 22).
• The primary efficacy endpoint was the proportion of subjects at Day 29 who achieved success, defined as an ISGA grade of Clear (score of 0) or Almost Clear (score of 1) with a 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 atopic dermatitits signs, and time to improvement in pruritus.
• More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement (trial 1: 32.8% vs 25.4%, P = 0.038; trial 2: 31.4% vs 18.0%, P < 0.001).
• More patients achieved ISGA scores of clear (0) or almost clear (1) with crisaborole at day 29 (trial 1: 51.7% vs 40.6%, P = 0.005; trial 2: 48.5% vs 29.7%, P < 0.001).
• Kaplan-Meier analysis demonstrated that patients treated with crisaborole achieved success in ISGA score earlier than those treated with vehicle ointment (P < 0.001).
• Across all visits, a greater proportion of crisaborole-treated patients achieved improvement in pruritus compared with vehicle treated patients (pooled data, days 8, 15, 22: P < 0.001; day 29: P = 0.002).
• For all clinical signs of atopic dermatitis, a greater proportion of crisaborole-treated patients than vehicle-treated patients demonstrated improvement at day 29 (pooled data, days 8, 15, 22: erythema P < 0.001; exudation P = 0.001; excoriation P < 0.001; induration P = 0.002; lichenification P < 0.001).
• Table 1 provides a summary of success in IGSA score results from two clinical trials 1 and 2.

Table 1

Table 2

Next steps with crisaborole

• Crisaborole represents a promising new option for patients with mild to moderate atopic dermatitis based on the favorable safety profile and improvement in atopic dermatitis as seen in clinical trials.
• Future analysis using the Eczema Area and Severity Index should provide additional efficacy information by anatomic region to further the understanding on the role of crisaborole in the treatment of atopic dermatitis.
• 45–60% of children develop atopic dermatitis in their first 6 months to first year of life, and future studies should explore the potential for crisaborole treatment in patients younger than 2 years of age.
• Currently there are no clinical trials comparing the efficacy of crisaborole ointment with other atopic dermatitis treatments such as topical corticosteroids and topical calcineurin inhibitors.
• The long-term safety of topical crisaborole ointment needs to be evaluated.

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We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).