Topical TYK2/JAK 1 inhibitor effective and tolerable in mild-to-moderate AD

There is a high medical need for patients with mild-to-moderate atopic dermatitis (AD). According to a phase 2b study, brepocitinib cream could be an interesting novel option for these patients. The brepocitinib cream showed a significant decrease in EASI score at week 6 compared with a vehicle cream, as well as a higher rate of EASI 90 response and a fast and significant antipruritic effect.

The topical tyrosine kinase (TYK)2/Janus kinase (JAK)1 inhibitor brepocitinib is a single-molecule designed to target 2 key pathways that play a role in both psoriasis and AD. Inhibition of TYK2 blocks the Th17 axis that is important in psoriasis but also in specific forms of AD,  for example in Asian patients and in paediatric new-onset AD. In contrast, inhibition of JAK1 blocks the Th2-pathway, the relevant pathway in AD of European and American patients.

Prof. Megan Landis (University of Louisville School of Medicine, USA) presented promising results of a double-blind, vehicle-controlled phase 2b study that assessed the efficacy and safety of topical brepocitinib in patients with mild to moderate AD. Overall, 292 adult and adolescent AD patients with mild-to-moderate disease (i.e. Investigators Globals Asessment [IGA] 2-3, Eczema Area and Severity Index [EASI] total score ≥ 3to ≤21) were randomised and received at least 1 dose of the study drug or vehicle cream. The study period of 6 weeks was completed by 240 patients. The primary endpoint was the percentage change from baseline in EASI total score at week 6. In addition, the EASI 90 response and the proportion of participants achieving an IGA score of clear (0) or almost clear (1) skin and a reduction from baseline of ≥2 points at week 6 were assessed as secondary endpoints.

At week 6, a significant decrease from baseline in EASI score was seen with the cream that contained 1% brepocitinib, which was the highest dose tested in the study. When brepocitinib was applied twice daily there was a 75% decrease in EASI score at week 6 compared with 47.6% in the vehicle group. A significant treatment response was also seen in the secondary endpoints. Patients treated with the cream containing 0.3%, 1.0%, and 3.0% brepocitinib achieved significantly more often an EASI 90 response at week 6 compared with the vehicle group. A significantly higher percentage of patients in all brepocitinib groups achieved an IGA 0/1 response at week 6.

The influence on pruritus, a symptom particularly bothering AD patients was also assessed as the percentage of participants achieving a ≥4-grade reduction from baseline (among those with baseline ≥4 in severity on the peak pruritus numerical rating scale). “A significant effect on pruritus was noticed in the 2 highest doses,” Prof. Landis said. This reduction was achieved by 50% of the participants treated once-daily with the 3% brepocitinib cream.

“With regard to safety, we noticed no side effects that increased with dose. We also had no serious adverse events and no lab changes,” Prof. Landis reported. Of note, more patients in the vehicle group had side effects or discontinued the study due to treatment-emergent adverse events than in the brepocitinib groups. “This trial supports the use of this novel agent for patients with mild-to-moderate AD,” Prof. Landis concluded.

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   1. Landis M, et al. A Phase 2b study to evaluate the efficacy and safety of the topical TYK2/JAK1 inhibitor brepocitinib for mild-to-moderate atopic dermatitis. Late-breaking abstract D1T03.4D, EADV Virtual, 29-31 October 2020.