Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Veterans Affairs (VA) Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
Am J Gastroenterol. 2018 Feb;113(2):276-282. doi: 10.1038/ajg.2017.438. Epub 2017 Dec 12.
In patients with inflammatory bowel disease (IBD) using biological therapy, non-adherence leads to anti-drug antibody formation and reduced effectiveness. Little is known about the optimal level of adherence in IBD patients on biologic therapy. We aimed to identify the association between adherence and disease flare and determine an optimal level of adherence.
We analyzed claims data for IBD patients prescribed adalimumab (ADA) and certolizumab (CZP) from the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. Adherence was calculated using the medication possession ratio (MPR) from initiation until flare occurrence. A disease flare was defined as any hospitalization or new steroid prescription>90-days after drug initiation. The optimal MPR was determined using log-rank testing. The association between the optimal MPR and flare was assessed using multivariable Cox-Proportional hazards ratio.
There were 6,048 patients who were prescribed ADA (n=5,325) or CZP (n=723) for IBD. The average age was 41 years (±15) and 54% were female. The optimal MPR identified was 0.86 for ADA and 0.87 for CZP; 24% of the patients were below this level. Adjusting for age, gender, and concomitant medications at initiation, patients who were adherent above these levels had a 25% lower risk of flare for ADA (HR: 0.75, 95%CI: 0.67-0.83, P<0.01) and 41% lower risk for CZP (HR: 0.59, 95%CI: 0.46-0.76, P<0.01).
Patients who delay refills >2 days on average every 2 weeks of their subcutaneous biologics have significantly increased risk of flare. Further studies to improve adherence among those patients who consistently delay medication use are necessary.
在使用生物疗法治疗炎症性肠病（IBD）的患者中，不依从会导致抗药物抗体的形成和疗效降低。对于生物疗法治疗的 IBD 患者的最佳依从水平知之甚少。我们旨在确定依从性与疾病发作之间的关系，并确定最佳的依从性水平。
我们分析了 2009 年至 2013 年 Truven Health MarketScan 商业索赔和遭遇数据库中开阿达木单抗（ADA）和 certolizumab（CZP）处方的 IBD 患者的索赔数据。依从性使用从开始到发作期间的药物占有率（MPR）来计算。疾病发作定义为药物起始后>90 天的任何住院或新的类固醇处方。使用对数秩检验确定最佳 MPR。使用多变量 Cox 比例风险比评估最佳 MPR 与发作之间的关联。
共有 6048 名患者被开 ADA（n=5325）或 CZP（n=723）治疗 IBD。平均年龄为 41 岁（±15），54%为女性。确定的最佳 MPR 为 ADA 为 0.86，CZP 为 0.87；24%的患者低于此水平。调整起始时的年龄、性别和伴随药物后，依从性高于这些水平的患者 ADA 发作的风险降低 25%（HR：0.75，95%CI：0.67-0.83，P<0.01），而 CZP 发作的风险降低 41%（HR：0.59，95%CI：0.46-0.76，P<0.01）。
平均每两周皮下生物制剂漏服超过 2 天的患者，发作风险显著增加。需要进一步研究以提高那些经常延迟用药的患者的依从性。
