Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real-life clinical practice
Por:
Butrón-Bris, B, Llamas-Velasco, M, Ovejero-Benito, MC, Santos-Juanes, J, Martínez-López, A, Ruiz-Villaverde, R, Roustan, G, Baniandrés, O, Izu-Belloso, R, de la Cueva, P, Sahuquillo-Torralba, A, Gónzalez-Quesada, A, Vilarrasa-Rull, E, Pujol-Montcusi, J, García-Martínez, J, Navares, M, Palomar-Moreno, I, Novalbos, J, Abad-Santos, F, Daudén, E, de la Fuente, H
Publicada:
1 ago 2024
Resumen:
Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI <= 1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI <= 1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI <= 1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
Filiaciones:
Butrón-Bris, B:
Hosp Univ Princesa, Serv Dermatol, Inst Invest Sanit Princesa, Madrid, Spain
Llamas-Velasco, M:
Hosp Univ Princesa, Serv Dermatol, Inst Invest Sanit Princesa, Madrid, Spain
Ovejero-Benito, MC:
CEU Univ Madrid, Univ San Pablo, Fac Farm, Dept Ciencias Farmaceut & Salud,CEU, Madrid, Spain
Santos-Juanes, J:
Hosp Univ Cent Asturias, Dept Dermatol, Asturias, Spain
Univ Oviedo, Grp Invest Dermatol GRIDER, Oviedo, Spain
Martínez-López, A:
Hosp Univ Virgen Nieves, Dept Dermatol, Granada, Spain
Ruiz-Villaverde, R:
Hosp Univ San Cecilio, Dept Dermatol, Granada, Spain
Roustan, G:
Hosp Univ Puerta Hierro, Dept Dermatol, Madrid, Spain
Baniandrés, O:
Hosp Gen Univ Gregorio Maranon, Dept Dermatol, Madrid, Spain
Izu-Belloso, R:
Hosp Univ Basurto, Dept Dermatol, Bilbao, Spain
de la Cueva, P:
Hosp Univ Infanta Leonor, Dept Dermatol, Madrid, Spain
Sahuquillo-Torralba, A:
Hosp Univ & Politecn La Fe, Dept Dermatol, Inst Invest Sanit Fe, Valencia, Spain
Gónzalez-Quesada, A:
Hosp Univ Gran Canaria Doctor Negrin, Dept Dermatol, Las Palmas Gran Canaria, Spain
Vilarrasa-Rull, E:
Hosp Santa Creu & Sant Pau, Dept Dermatol, Barcelona, Spain
Pujol-Montcusi, J:
Hosp Univ Tarragona Joan XXIII, Dept Dermatol, Tarragona, Spain
García-Martínez, J:
Hosp Univ Nino Jesus, Inst Invest Sanit Princesa, Madrid, Spain
Navares, M:
Univ Autonoma Madrid, Hosp Univ Princesa, Clin Pharmacol Dept, Inst Invest Sanit Princesa, Madrid, Spain
Palomar-Moreno, I:
Inst Invest Sanit Princesa, Unit Mol Biol, Madrid, Spain
Novalbos, J:
Univ Autonoma Madrid, Hosp Univ Princesa, Clin Pharmacol Dept, Inst Invest Sanit Princesa, Madrid, Spain
Abad-Santos, F:
Univ Autonoma Madrid, Hosp Univ Princesa, Clin Pharmacol Dept, Inst Invest Sanit Princesa, Madrid, Spain
Daudén, E:
Hosp Univ Princesa, Serv Dermatol, Inst Invest Sanit Princesa, Madrid, Spain
de la Fuente, H:
Hosp Univ Princesa, Serv Dermatol, Inst Invest Sanit Princesa, Madrid, Spain
Inst Invest Sanit Princesa, Unit Mol Biol, Madrid, Spain
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