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真实世界中炎症性肠病患者的生物制剂使用模式:治疗持久性、转换及同时应用免疫抑制治疗的重要性。

Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy.

机构信息

Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA.

出版信息

Inflamm Bowel Dis. 2019 Jul 17;25(8):1417-1427. doi: 10.1093/ibd/izz001.

Abstract

BACKGROUND AND AIMS

Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD).

METHODS

Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression.

RESULTS

In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% in UC cohort). In the first year, adalimumab had the highest persistence and lowest switching rates for both CD (median survival time: 1.04 years) and UC (median survival time: 0.84 years). In subsequent years, infliximab users were more likely to persist in the use of biologic. Combination therapy with immunomodulators significantly decreased the risk of discontinuation, especially when immunomodulator therapy was started more than 30 days before the biologic (hazard ratio [HR], 0.22; CI, 0.16, 0.32). The major predictors for noncompliance included infection and hospitalization.

CONCLUSION

Overall, the persistence profiles of biologics suggest a high rate of dissatisfaction or adverse disease outcomes resulting in discontinuation and switching to a different agent. Early initiation of immunomodulators will substantially increase the persistence of biologic treatment.

摘要

背景与目的

药物持久性(定义为从开始用药到停止治疗的时间)已被认为是评估真实世界治疗获益和安全性的替代指标。本研究旨在比较炎症性肠病(IBD)患者接受生物制剂治疗的持久性。

方法

本回顾性研究使用 Truven MarketScan 数据库纳入新诊断为 IBD 的患者。比较了包括英夫利昔单抗、阿达木单抗、依那西普、戈利木单抗和维得利珠单抗在内的生物制剂的治疗持久性和转换情况。使用时变比例风险回归评估停药和转换的预测因素。

结果

共纳入 5612 例克罗恩病(CD)患者和 3533 例溃疡性结肠炎(UC)患者。不到一半的患者在 1 年内继续使用初始生物制剂治疗(CD 队列中为 48.48%;UC 队列中为 44.78%)。在第一年,阿达木单抗在 CD(中位生存时间:1.04 年)和 UC(中位生存时间:0.84 年)中具有最高的持久性和最低的转换率。在随后的几年中,英夫利昔单抗使用者更有可能持续使用生物制剂。免疫调节剂联合治疗可显著降低停药风险,尤其是当免疫调节剂治疗开始时间超过生物制剂 30 天以上时(风险比 [HR],0.22;CI,0.16,0.32)。不依从的主要预测因素包括感染和住院治疗。

结论

总体而言,生物制剂的持久性表明,由于不满意或不良疾病结局,导致停药和转换为不同药物的比例较高。早期开始使用免疫调节剂将显著提高生物制剂治疗的持久性。

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