肿瘤坏死因子-α抑制剂治疗多种免疫炎性疾病的疗效:以免疫原性为重点

T. Y. Nuriahmetova, I. Valeeva, Y. Shevnina, A. Petrov, N. Cheremina, E. Sukhorukova, A. G. Vasiliev, D. Abdulganieva
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摘要

在临床实践中,已观察到肿瘤坏死因子-α抑制剂(iTNF-α)在不同疾病中的疗效差异。目的:评价iTNF-α治疗免疫介导性疾病的疗效及其与药物免疫原性的关系。材料和方法。该研究包括70例风湿病(RD)患者和53例炎症性肠病(IBD)患者,他们接受英夫利昔单抗(IFN)、阿达木单抗或certolizumab pegol (CZP)治疗。评估疾病活动性和对治疗的反应,以及测量iTNF-α的最小残留浓度和抗药物抗体水平。结果和讨论。60例RD患者(85.7%)和35例IBD患者(66.0%)的治疗效果保持不变(优势比,OR 1.3;p = 0.01)。治疗无事件生存期在RD组比IBD组更常见且更长(p<0.01)。IBD组治疗失败的发生率是RD组的3.13倍(p<0.01)。与IBD相比,低TNF-α水平在治疗无反应的RD患者中比治疗有反应的RD患者更常见(分别为80%和40%;或6.0;p < 0.05)。在RD组中,75%的INF和CZP治疗无效的患者检测到抗tnf -α抗体,在IBD组中为14.3% (OR 0.06;.Conclusion p < 0.05)。在RD患者中,iTNF-α的作用比IBD患者更频繁,持续时间更长。在强直性脊柱炎和类风湿关节炎中,iTNF-α的无效在大多数情况下与抗药物抗体的形成或其低浓度有关,但在IBD中仅占一半。
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Efficacy of tumor necrosis factor-α inhibitors in the treatment of various immunoinflammatory diseases: focus on immunogenicity
In clinical practice, differences in the efficacy of tumor necrosis factor-α inhibitors (iTNF-α) have been observed in different diseases.Objective: to evaluate the efficacy of iTNF-α in patients with immune-mediated diseases and its relation to the immunogenicity of these drugs.Material and methods. The study included 70 patients with rheumatic diseases (RD) and 53 with inflammatory bowel disease (IBD) treated with infliximab (IFN), adalimumab, or certolizumab pegol (CZP). Disease activity and response to therapy were evaluated, as well as measurement of the minimal residual concentration of iTNF-α and the level of anti-drug antibodies.Results and discussion. Therapy efficacy was maintained in 60 (85.7%) patients with RD and 35 (66.0%) with IBD (odds ratio, OR 1.3; p=0.01). Event-free survival of therapy was observed more frequently in RD and was longer than in IBD (p<0.01). The incidence of treatment failure was 3.13 times higher in IBD than in RD (p<0.01). In contrast to IBD, low TNF-α levels were more common in RD patients who did not respond to treatment than in those who did (80% and 40%, respectively; OR 6.0; p<0.05). Anti-TNF-α antibodies were detected in 75% of patients with ineffective treatment with INF and CZP in the RD group and in 14.3% in the IBD group (OR 0.06; p<0.05).Conclusion. In patients with RD, the effect of iTNF-α lasted more frequently and longer than in patients with IBD. In ankylosing spondylitis and rheumatoid arthritis, the ineffectiveness of iTNF-α was associated with the formation of anti-drug antibodies or their low concentration in most cases, but in IBD only in half of the cases.
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