背景:比较有效性研究提供了有关治疗之间相对益处和风险的数据。在克罗恩病,然而,很少有正面对正面的研究比较先进的疗法,没有长期随访.现实世界的有效性,由治疗持久性定义,从前瞻性基于人群的患者队列中获得可能有助于确定生物制剂的最佳测序和定位.
方法:我们分析了前瞻性收集的基于人群的澳大利亚国家药物福利计划配药数据注册表(2005-2019)的CD。没有强制性的生物制剂处方令,所有公民和永久居民都有资格接受治疗,无论其保险状况如何。进行倾向评分匹配以减少选择偏倚。
结果:1,446例患者中有2,029行治疗(中位年龄43岁,IQR:34-58,男性44%)在15年内进行了5,618患者年的随访。每行治疗,915/2,029(45.1%)患者使用阿达木单抗,722/2,029(35.6%)使用英夫利昔单抗,155/2,029(7.6%)使用维多珠单抗,237/2,029(11.7%)使用了ustekinumab。当用于生物制剂初治患者时,任何药物之间的持久性无差异(P>0.05)。使用后一线在生物制剂-经验丰富的CD,ustekinumab的持久性明显优于非ustekinumab生物制剂(P=0.0018),抗肿瘤坏死因子(TNF)α治疗(P=0.006)或维多珠单抗(P<0.001)。Ustekinumab的持久性不受先前生物制剂暴露的影响(P=0.51)。使用抗TNF后,乌司他单抗的持久性优于替代的抗TNF药物(P=0.033)和维多珠单抗(P=0.026)。使用根据年龄调整的倾向评分匹配分析,免疫调节剂的使用和生物暴露状态,乌司他单抗的持久性优于抗TNF(P=0.01)。持久性较差的多变量预测因素是使用非ustekinumab生物制剂(调整后的风险比(aHR):2.10,P<0.001),和生物经历状态(aHR:1.23,P<0.001)。
结论:这个大型的国家前瞻性数据库,使用非分级的生物制剂处方,没有发现任何药物在生物初始CD中的持久性。然而,对于有生物经验的CD患者,ustekinumab的持久性更大.
BACKGROUND: Comparative effectiveness research provides data on the relative benefits and risks between treatments. In Crohn\'s disease (CD), however, there are few head-to-head studies comparing advanced therapies and none with long-term follow-up. Real-world effectiveness, defined by treatment persistence, obtained from prospective population-based patient cohorts, may help determine the best sequencing and positioning of biological agents.
METHODS: We analyzed the prospectively collected population-based Australian national Pharmaceutical Benefits Scheme dispensing data registry (2005-2019) for CD. There is no mandated biological agent prescribing order, and all citizens and permanent residents are eligible for treatment irrespective of insurance status. Propensity score matching was performed to reduce selection bias.
RESULTS: There were 2,029 lines of therapy in 1,446 patients (median age 43 years, interquartile range 34-58, 44% male patients) over the 15-year period with 5,618 patient-years of follow-up. Per line of therapy, 915/2,029 (45.1%) patients used adalimumab, 722/2,029 (35.6%) used infliximab, 155/2,029 (7.6%) used vedolizumab, and 237/2,029 (11.7%) used ustekinumab. When used in biological agent-naive patients, there was no difference in persistence between any agent ( P > 0.05). Used after first line in biological agent-experienced CD, ustekinumab had significantly better persistence than non-ustekinumab biological agents ( P = 0.0018), vs anti-tumor necrosis factor (TNF) alpha therapy ( P = 0.006) or vedolizumab ( P < 0.001). Ustekinumab persistence was unaffected by prior biological agent exposure ( P = 0.51). After anti-TNF use, ustekinumab had superior persistence to an alternative anti-TNF agent ( P = 0.033) and to vedolizumab ( P = 0.026). Using a propensity score-matched analysis adjusted for age, immunomodulator use, and bio-exposed status, ustekinumab had superior persistence to anti-TNF ( P = 0.01). Multivariate predictors of worse persistence were the use of a non-ustekinumab biological agent (adjusted hazard ratio 2.10, P < 0.001), and bio-experienced status (adjusted hazard ratio 1.23, P < 0.001).
CONCLUSIONS: This large national prospective database with nonhierarchical prescribing of biological agents did not identify superior persistence of any agent in bio-naive CD. However, for patients with bio-experienced CD, persistence was greater with ustekinumab.