Genetic polymorphisms in psoriasis: investigating genetic variations for precise profiling of response to brodalumab in real-life clinical practice.

Background: Numerous studies have investigated the association that exists between genetic variants and the efficacy profile of biologic therapies for the management of psoriasis. However, as far as we know, data on this association for brodalumab are lacking in the currently available scientific literature.

Objective: To analyze the association of 180 polymorphisms with an optimal response to brodalumab in real-world clinical practice.

Methods: A total of 119 patients with plaque psoriasis on a 24-regimen of brodalumab recruited from 11 Spanish hospitals were genotyped for 180 polymorphisms. Optimal response was evaluated as absolute (PASI) ≤ 1 at 6 and 12 months. Polymorphisms with false discovery rates < 0.25 were included in a multiple regression model.

Results: A total of 68% and 62% of patients achieved PASI ≤ 1 at 6 and 12 months, respectively. Patient weight, history of biological therapy, disease-modifying anti-rheumatic drugs, and psoriatic arthritis were identified as risk factors for failing to achieve PASI ≤1. At 12 months, polymorphisms rs495337 (SPATA2), rs6311 (HTR2A), and rs4085613 (LCE3D) were associated with achieving a PASI ≤1 regardless of previous use of biologics and DMARDs, psoriatic arthritis, or weight. The genotypes CT-TT for rs6311 (HTR2A) and GT for rs4085613 (LCE3D) were identified as risk factors for lack of optimal response at 12 months, while genotypes AG-AA for rs495337 (SPATA2) increase the probability of response. No polymorphism was associated to brodalumab response at 6 months.

Conclusions: This study identified genetic variations associated with the ability to achieve an optimal response to brodalumab, providing potential insights into its efficacy profile for treating plaque psoriasis.