Key evidence from clinical trials for crisaborole

Introduction

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

Crisaborole approval was based on the results of two large, identical, multicentre, randomized, double-blind, parallel, vehicle-controlled group trials (unmedicated ointment) (Trials 1 and 2) treating 1522 patients aged 2 to 79 years with mild to moderate atopic dermatitis.

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

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

Important trials supporting the clinic effectiveness from crisaborole

• In two phase III studies, crisaborole ointment improved the severity of the disease and pruritus with a favorable safety profile in patients with mild to moderate atopic dermatitis.
• Two multicenter, randomized, double-blind, parallel group, vehicle controlled trials (Trials 1 and 2) treated a total of 1522 subjects aged 2 to 79 years (86.3% of subjects aged 2 to 17 years of age ) with a treatable 5–95% body surface area.
• TO base, 38.5% of the subjects had an Investigator Static Global Assessment [ISGA] score of 2 (mild), and 61.5% had an ISGA score of 3 (moderate), in the general evaluation of atopic dermatitis (erythema, hardening/ papulation and exudation /crust) in a gravity scale 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 injury twice a day during the 28-day study in all affected areas at the start of the study.
• The scalp was excluded from treatment to avoid possible patient dissatisfaction with applying ointment to the scalp. hair.
• Patients were reviewed at weekly scheduled clinic visits (days 8, 15, and 22).
• the primary The efficacy end point was the proportion of subjects on day 29 who achieved success, defined as an ISGA grade of Clear (score of 0) or Almost Clear (score of 1) with improvement of 2 degrees or greater from baseline .
• Additional analyzes included the time to success on the ISGA score, the percentage of patients achieving a clear / nearly clear reduction in the severity of signs of atopic dermatitis, and the time to improve itching.
• More patients treated with crisaborole than with vehicle achieved a successful ISGA score (clear / almost clear with an improvement of ≥2 degrees (trial 1: 32.8% vs 25.4%, P = 0.038; test 2: 31.4% vs 18.0%, P <0.001).
• More patients achieved ISGA scores of clear (0) or near clear (1) with crisaborole on day 29 (trial 1: 51.7% vs 40.6%, P = 0.005; test 2: 48.5% vs 29.7%, P <0.001).
• The Kaplan-Meier analysis showed that patients treated with chrysaborole achieved an ISGA score success earlier than those treated with vehicle ointment (P <0.001).
• At all visits, a higher proportion of patients treated with crisaborole achieved an improvement in itching compared to 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 higher proportion of chrysaborole-treated patients than vehicle-treated patients showed improvement on day 29 (pooled data, days 8, 15, 22: erythema. P <0.001; exudation P = 0.001; excoriation P <0.001; hardening P = 0.002; lichenification P <0.001).
• Table 1 provides a summary of the success in the IGSA score results of two clinical trials 1 and 2.

See below Table 1 and 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 of atopic dermatitis as seen in clinical trials.
• Future analysis using the Eczema The area and severity index should provide additional efficacy information by anatomical region to better understand the role of crisaborole in the treatment of atopic dermatitis.
• 45-60% in children develop atopic dermatitis in the first 6 months to the first year of life, and future studies should explore the potential of crisaborole treatment in patients younger than 2 years.
• There are currently no clinical trials comparing the efficacy of crisaborole ointment with other treatments for atopic dermatitis, such as topical corticosteroids and topical calcineurin inhibitors.
• The long-term safety of crisaborole topical ointment should be evaluated.