背景:我们旨在评估临床疗效,生物标志物活性,治疗药物监测(TDM),不良事件(AE),和nocebo效应在炎症性肠病(IBD)患者谁经历了非医学生物类似药转换。
方法:一项对连续IBD患者进行生物仿制药转换的前瞻性观察性研究。疾病活动,生物标志物,TDM,和AEs,包括在切换前8周捕获的nocebo效应,在切换时(基线),切换后12周和24周。
结果:包括210例患者[81.4%患有克罗恩病(CD),纳入时的中位年龄:42岁(IQR29-61)]。转换前第8周的临床缓解率没有显着差异,基线,第12周和第24周切换后:89.0%,93.4%,86.3%,90.8%,p=0.129。生物标志物缓解率无显著差异;CRP:81.3%,74.7%,81.2%,73.0%,p=0.343;粪便钙卫蛋白:78.3%,74.5%,71.7%,76.3%,p=0.829。维持治疗水平的比率(84.7%,83.9%,83.0%,85.3%,p=0.597),抗药物抗体阳性的患病率保持不变。转换12周时的药物持久性为97.1%,无论疾病表型和起源。在13.3%中观察到nocebo效应。停药率为4.8%。
结论:尽管在生物仿制药转换后的前6个月内出现了大量的早期nocebo投诉,临床疗效无明显变化,生物标志物,治疗药物水平,或抗药物抗体。
BACKGROUND: We aimed to evaluate clinical efficacy, biomarker activity, therapeutic drug monitoring (TDM), adverse events (AEs), and nocebo effect in inflammatory bowel disease (IBD) patients who underwent non-medical biosimilar switching.
METHODS: A prospective observational study of consecutive IBD patients who underwent biosimilar switch. Disease activity, biomarkers, TDM, and AEs, including the nocebo effect were captured 8 weeks before switch, at the time of switch (baseline),12 and 24 weeks after the switch.
RESULTS: 210 patients were included [81.4% had Crohn\'s disease (CD), the median age at inclusion: 42 years (IQR 29-61)]. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week12, and 24 after switch: 89.0%,93.4%,86.3%,and 90.8%,p = 0.129. The biomarker remission rates were not significantly different; CRP:81.3%,74.7%,81.2%,73.0%,p = 0.343; fecal calprotectin: 78.3%,74.5%,71.7%,76.3%,p = 0.829. The rates of maintaining therapeutic levels (84.7%,83.9%,83.0%,85.3%,p = 0.597) and prevalence of positive anti-drug antibodies remained unchanged. Drug persistence at 12 week of switch was 97.1%, regardless of disease phenotype and originator. The nocebo effect was observed in 13.3%. The discontinuation rate was 4.8%.
CONCLUSIONS: Despite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, or anti-drug antibodies.