In a 2016 study, researchers sought to determine the safety and efficacy of crisaborole ointment for treatment of atopic dermatitis, an inflammatory skin condition. It was found that one month of crisaborole treatment reduces atopic dermatitis symptoms and speeds recovery in both children and adults.
Though the standard treatments for the chronic inflammatory skin condition known as atopic dermatitis (AD) are effective for the reduction of inflammation and the prevention of flare-ups, their limitations – notably, thinning of the skin with topical corticosteroid (TCS) use and an increased risk of lymphoma with topical calcineurin inhibitor (TCI) use – highlight the need for safe and effective new therapies. Recently, compounds which block the action of phosphodiesterase 4 (PDE4), an inflammation-promoting enzyme overproduced in AD-afflicted cells, have shown promise.
In a 2016 study published in the Journal of the American Academy of Dermatology, researchers investigated the safety and efficacy of the PDE4 inhibitor crisaborole for the treatment of AD. Data was collected and analyzed from 2 large US trials. Participants were 2 years or older with a clinical diagnosis of mild to moderate AD, with at least 5% treatable surface area on the skin. Those taking TCSs or TCIs within 14 days of the study or systemic (taken orally or injected) corticosteroids or biologic therapy within 28 days of the study were excluded. Stable use of inhaled corticosteroids, allergy medications, and moisturizers and Vitamin A-based creams on areas of the skin not afflicted with AD, however, were permitted to continue. Patients received either a crisaborole or placebo ointment which they or their caregivers were instructed to apply to each AD-afflicted region (except the scalp) twice daily for 28 days. Any new AD-afflicted regions that appeared after the start of the trials were to be treated with ointment as needed.
Efficacy was assessed with respect to changes in a patient’s Investigator’s Static Global Assessment (ISGA) score, which rates AD severity from 0 to 4; the severity of itchiness from 0 to 3; and signs of AD, particularly picking at the skin, oozing, redness, bumps or hardening, or leathery skin from 0 to 3. Safety was assessed with respect to adverse events and vital signs.
In total, 1016 patients (503 from Trial 1 and 513 from Trial 2) received crisaborole and 506 (256 from Trial 1 and 250 from Trial 2) received a placebo ointment. A 2-point improvement in ISGA score from 2 to 0 or 3 to 1 was achieved by 32.8% of crisaborole compared to 25.4% of placebo patients in Trial 1, and 31.4% versus 18.0% in Trial 2. ISGA scores of 0 or 1, regardless of starting score, were achieved by 51.7% of crisaborole compared to 40.6% of placebo patients in Trial 1 and 48.5% versus 29.7% in Trial 2. On average, crisaborole patients achieved ISGA scores of 0 or 1 several days sooner than their placebo-treated counterparts. Itchiness was reduced to a score of 0 or 1 in 16% more crisaborole patients than placebo patients after 8 and 15 days, 13% more after 22 days, and 10% more on day 29. Redness was reduced by 21%, oozing by 13%, skin picking by 18%, bumps and hardening by 8%, and leathery skin by 13% more for the crisaborole group than for the placebo group by day 29. A burning or stinging sensation at the site of application was experienced by 3.3% of patients – 45 of 51 of who received crisaborole – but did not last beyond one day for 77.6% of cases.
Overall, the study findings suggest crisaborole treatment reduces atopic dermatitis symptoms and speeds recovery in both children and adults. The associated side effects appear to be mild and short-lived. As such, crisaborole ointment has the potential to serve as a safe and effective treatment for AD. Future research may benefit from examining the long-term effects of treatment, especially in children between 6 months and 1 year (who make up the majority of new AD cases) and individuals with severe AD.
Written By: Raishard Haynes, MBS