By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a topical boron-containing phosphodiesterase 4 (PDE-4) inhibitor, crisaborole, for the treatment of atopic dermatitis. This PDE-4 subtype shows anti-inflammatory properties as do two other members of this class are roflumilast for COPD and apremilast for psoriasis. Crisaborole is marketed as Eucrisa.

INDICATIONS

Crisaborole is indicated for topical treatment of mild to moderate atopic dermatitis in patients 2 years of age.1

DOSAGE

The recommended dose is topical application (a thin layer) twice daily to affected area. Crisaborole is available as a 2% ointment.

POTENTIAL ADVANTAGES

Crisaborole provides a non-corticosteroid for the treatment of atopic dermatitis. It has low systemic exposure and is metabolized quickly to its inactive metabolites.1

POTENTIAL DISADVANTAGES

Crisaborole currently is not indicated for use on children < 2 years of age. The safety of long-term application has not been determined.

COMMENTS

Crisaborole’s anti-inflammatory action is believed to be due to its inhibition of PDE-4, which is the predominant cyclic AMP degrading enzyme.2 PDE-4 is overactive in inflammatory cells in patients presenting with atopic dermatitis.3

The efficacy and safety of crisaborole were evaluated in two identically designed, vehicle-controlled, double-blind, randomized studies.1,4 Subjects (n = 1,511) with mild (38.5%) and moderate (61.5%) atopic dermatitis were randomized 2:1 to crisaborole or vehicle twice daily for 28 days.

The primary efficacy endpoint, assessed at day 29, was the proportion of subjects who achieved success. Success was defined as an Investigator’s Static Global Assessment (ISGA) score of clear (0) or almost clear (1) with a 2-grade or more improvement from baseline. ISGA was a 4-point scale based on the degree of erythema, induration/papulation, and oozing/crusting.

Success rates were 32.8% for study one and 31.4% for study two compared to 25.4% and 18.0%, respectively, for vehicle-placebo. Improvement was seen by day eight, and a higher proportion of subjects on crisaborole showed greater reduction in erythema, exudations, excoriation, induration/papulations, and lichenification.4 Crisaborole is well tolerated, with burning and stinging at the application site reported in 4% of subjects, compared to 1% for the vehicle.

There are no published comparative trials comparing crisaborole and topical corticosteroids or calcineurin inhibitors (i.e., pimecrolimus, tacrolimus) at this time.

CLINICAL IMPLICATIONS

Atopic dermatitis is a common, chronic, pruritic, inflammatory skin disorder. The mainstay topical anti-inflammatory pharmacologic therapy is topical corticosteroids.5 Topical calcineurins are alternatives to corticosteroids if the latter was ineffective and caused adverse effects (e.g., atrophy).

Crisaborole is the first topical PDE-4 inhibitor to be approved for atopic dermatitis. It seems to be effective and well tolerated. It provides an alternative to topical corticosteroids and calcineurin inhibitors for atopic dermatitis in children ( 2 years of age) and adults.

Relative effectiveness to existing agents remains to be determined. The cost is not available at this time.

REFERENCES

  1. Eucrisa Prescribing Information. Anacor Pharmaceuticals, Inc. December 2016.
  2. Bäumer W, Hoppmann J, Rundfeldt C, Kietzmann M. Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Target 2007;6:17-26.
  3. Butler JM, Chan SC, Stevens S, Hanifin JM. Increased leukocyte histamine release with elevated cyclic AMP-phosphodiesterase activity in atopic dermatitis. J Allergy Clin Immunol 1983;71:490-497.
  4. Paller AS, Tom WL, Lebwohl MG, et al. 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. J Am Acad Dermatol 2016;75:494-503.
  5. Eichenfield LE, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol 2014;71:116-132.