背景:回顾抗TNF-α失去作用的频率和剂量“强化”是克罗恩病(CD)治疗所必需的。
方法:在电子数据库中搜索符合条件的研究。来自符合纳入标准的研究的原始数据被汇总用于效果估计。进行亚组分析以探索所有结果的异质性。
结果:纳入86项符合条件的研究。反应丧失(LOR)发生率的估计值为8%至71%。平均随访1年的LOR的随机效应合并发生率为33%(95%CI29-38,55项研究,n=6135)。基于英夫利昔单抗患者数据的疗效估计为33%(95%CI27-40),阿达木单抗的30%(95%CI22-39),和41%(95%CI30-53)的certolizumabpegol。总的来说,患者的LOR与抗TNF的平均百分比为38.5%.LOR的年风险为每患者年20.9%。中位随访1年的随机效应合并剂量强化需求率为34%(95%CI28-41,38项研究,n=10,690)。英夫利昔单抗的疗效估计为38%(95%CI28-50),阿达木单抗占36%(95%CI30-43),和2%(95%CI2-3)的赛托珠单抗-聚乙二醇。需要抗TNF剂量增加的患者的平均百分比为23%,每患者年的年风险为18.5%。没有证据表明LOR发生率的发表偏倚,但没有剂量增强的发表偏倚(p=0.001)。
结论:总体而言,约1/3的CD患者经历LOR,并在主要抗TNF-α反应者中需要剂量强化.
BACKGROUND: To
review the frequency with which anti-TNF-α loses its effect and dose \"intensification\" is required for Crohn\'s disease (CD) treatment.
METHODS: Electronic databases were searched for eligible studies. Raw data from studies meeting inclusion criteria were pooled for effect estimates. Subgroup analyses were performed for exploration of heterogeneity regarding all outcomes.
RESULTS: Eighty-six eligible studies were included. Estimates of loss of response (LOR) incidence ranged from 8 to 71%. The random effects pooled incidence of LOR with a median follow-up of 1-year was 33% (95% CI 29-38, 55 studies, n = 6135). The effect estimate based on data from patients with infliximab was 33% (95% CI 27-40), 30% (95% CI 22-39) for adalimumab, and 41% (95% CI 30-53) for certolizumabpegol. Overall, the mean percentage of patients\' LOR to anti-TNFs was 38.5%. The annual risk for LOR was 20.9% per patient-year. The random-effects pooled rate of need for dose intensification with a median follow-up of 1 year was 34% (95% CI 28-41, 38 studies, n = 10,690). The effect estimate for infliximab was 38% (95% CI 28-50), 36% (95% CI 30-43) for adalimumab, and 2% (95% CI 2-3) for certolizumab-pegol. The mean percentage of patients who needed an anti-TNF dose escalation was 23% with an annual risk of 18.5% per patient-year. There was no evidence of publication bias for incidence of LOR but not for the dose intensification (p = 0.001).
CONCLUSIONS: Overall, around one-third of CD patients experience a LOR and required dose intensification in primary anti-TNF-α responders.