Rottura Michelangelo, Pirrotta Igor, Giorgi Domenico Antonio, Irrera Natasha, Arcoraci Vincenzo, Mannino Federica, Campisi Rosario, Bivacqua Chiara, Patanè Laura, Costantino Giuseppe, Pallio Socrate, Fries Walter, Viola Anna, Pallio Giovanni
Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy.
Department of Medicine and Surgery, University of Enna "Kore", Contrada Santa Panasia, 94100 Enna, Italy.
Biomedicines. 2025 Mar 8;13(3):669. doi: 10.3390/biomedicines13030669.
Tumor necrosis factor alpha (TNF-α) is the key inflammatory cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). Anti-TNF-α therapy has been successfully used for IBD treatment, although the therapeutic response differs among patients due to the genetic background. The aim of this study was to investigate whether the presence of single nucleotide polymorphisms (SNPs) on , , and genes could affect anti-TNF-α treatment effectiveness in IBD patients. In this prospective cohort study, 83 European IBD patients treated with infliximab or adalimumab (with or without steroid bridge therapy) as first-line therapy were enrolled. Genomic DNA was extracted from peripheral blood, and (rs1800629, rs361525, rs1799724), (rs767455), and (rs1061622, rs1061624, rs3397, rs976881) SNPs were assessed. Steroid-free remission (SFR) (clinical remission together with steroid interruption) and anti-TNF-α therapy persistence after 12 months of follow-up were evaluated. Patients who stopped anti-TNF-α therapy before the end of follow-up, due to side effects or treatment failure, were defined as discontinuers. A higher frequency of the G/G genotype in rs1800629 and the A/A genotype in rs1061624 was observed in the SFR group compared to non-SFR (97.7% vs. 82.8%; = 0.025 and 32.6% vs. 10.3%; = 0.029, respectively). Moreover, carriers of the A/A genotype in rs361525 and the C/C genotype in rs767455 had a lower probability of achieving SFR than wild-type patients (OR = 0.14; 95% CI= 0.03-0.69; = 0.016 and OR = 0.10; 95% CI = 0.02-0.60; = 0.012, respectively). Furthermore, an increased frequency of rs1800629 A allele was observed in patients who discontinued treatment compared to completers (27.3% vs. 6.9%; = 0.033), as well as a high risk of interrupting therapy (HR = 6.47; 95% CI = 1.15-36.38). These results suggest that the evaluation of SNPs in , , and genes could improve the management of IBD, leading to more effective, individualized treatment plans and a reduction in healthcare costs associated with ineffective therapies and disease complications.
肿瘤坏死因子α（TNF-α）是参与炎症性肠病（IBD）发病机制的关键炎性细胞因子。抗TNF-α疗法已成功用于IBD治疗，尽管由于遗传背景不同，患者的治疗反应存在差异。本研究的目的是调查 、 和 基因上的单核苷酸多态性（SNP）是否会影响IBD患者抗TNF-α治疗的有效性。在这项前瞻性队列研究中，纳入了83例接受英夫利昔单抗或阿达木单抗（有或无类固醇桥接治疗）作为一线治疗的欧洲IBD患者。从外周血中提取基因组DNA，并评估 （rs1800629、rs361525、rs1799724）、 （rs767455）和 （rs1061622、rs1061624、rs3397、rs976881）SNP。评估无类固醇缓解（SFR）（临床缓解并停用类固醇）以及随访12个月后抗TNF-α治疗的持续时间。因副作用或治疗失败在随访结束前停止抗TNF-α治疗的患者被定义为停药者。与非SFR组相比，SFR组中rs1800629的G/G基因型和rs1061624的A/A基因型频率更高（分别为97.7%对82.8%；P = 0.025和32.6%对10.3%；P = 0.029）。此外，rs361525的A/A基因型携带者和rs767455的C/C基因型携带者实现SFR的概率低于野生型患者（OR = 0.14；95%CI = 0.03 - 0.69；P = 0.016和OR = 0.10；95%CI = 0.02 - 0.60；P = 0.012）。此外，与完成治疗的患者相比，停药患者中rs1800629 A等位基因的频率增加（27.3%对6.9%；P = 0.033），以及中断治疗的高风险（HR = 6.47；95%CI = 1.15 - 36.38）。这些结果表明，评估 、 和 基因中的SNP可以改善IBD的管理，制定更有效、个性化的治疗方案，并降低与无效治疗和疾病并发症相关的医疗成本。
