Servicio de Dermatología, Instituto de Investigación Sanitaria La Princesa, Hospital Universitario de la Princesa, Madrid, Spain.
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU, CEU Universities Madrid, Madrid, Spain.
Exp Dermatol. 2024 Aug;33(8):e15152. doi: 10.1111/exd.15152.
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.
检测遗传变异与生物治疗反应的关联代表了开发个体化治疗的重要进展。本研究旨在研究银屑病患者中多态性与替度鲁单抗最佳反应的相关性，这是在真实临床实践中进行的。从西班牙医院招募了 90 名接受替度鲁单抗治疗至少 24 周的斑块状银屑病患者，对其进行了 180 个多态性的基因分型。通过 6 个月和 12 个月时绝对 PASI≤1 评估替度鲁单抗的最佳反应。将经过体重和疾病持续时间校正、 FDR<0.15 的多态性纳入多元回归模型。63%的患者在 6 个月时达到绝对 PASI≤1，71%的患者在 12 个月时达到。疾病持续时间（>27 年）和体重（>76 公斤）与治疗反应相关；校正这些因素后，在 6 个月时，多态性与替度鲁单抗反应之间没有相关性（FDR>0.15）。在 12 个月时的分析确定了 rs610604（TNFAIP3）的基因型 GG、rs9373839（ATG5）的 CT 型和 rs72167053（PDE4D）的 delCTGT/delCTGT 型为未达到最佳反应（PASI≤1）的危险因素，而 rs708567（IL17RC）的 CT 型是保护性的，与体重和疾病持续时间无关（FDR<0.15）。在 12 个月时的最终多变量模型显示 AUC 为 0.90（95%CI 0.82 至-0.98）。我们确定了一组多态性，可以帮助在真实实践条件下识别在 12 个月时对替度鲁单抗有最佳反应的银屑病患者。
