Transient receptor potential vanilloid subfamily, member 1 ( TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis ( AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown.
To assess the clinical efficacy and safety of PAC‐14028, a TRPV1 antagonist, via topical application in patients with AD.
In this 8‐week, phase IIb, randomized, double‐blind, multicentre, vehicle‐controlled study, patients with mild‐to‐moderate AD were randomized to receive PAC‐14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment ( IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis ( SCORAD) index and Eczema Area and Severity Index ( EASI) 75/90.
A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC‐14028 cream 0·1% ( P = 0·0025 vs. vehicle), 38·30% for PAC‐14028 cream 0·3% ( P = 0·0087 vs. vehicle) and 57·45% for PAC‐14028 cream 1·0% ( P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two‐grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported.
What is already known about this topic?
Atopic dermatitis ( AD) is one of the most common inflammatory skin diseases characterized by pruritic erythematous skin lesions and barrier dysfunction.
Transient receptor potential vanilloid subfamily, member 1 ( TRPV1) antagonists suppress the release of pruritic and proinflammatory mediators.
The preclinical results demonstrate the feasibility of TRPV1 as a potential therapeutic target for the treatment of AD.
What does this study add?
TRPV1 regulates inflammation and pruritus in patients with AD.
PAC‐14028 cream, a novel TRPV1 antagonist, was superior to vehicle in improving clinical symptoms and signs with a favourable safety profile in adults with mild‐to‐moderate AD.
TRPV1 antagonism may play a role as a promising nonsteroidal topical treatment target for AD with a new mechanism of action.
Linked Editorial: https://doi.org/10.1111/bjd.17777.
https://doi.org/10.1111/bjd.17802 available online