College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Apotex Centre, 750 McDermot Avenue, Winnipeg, MB, R3E 0T5, Canada.
School of Pharmacy, Memorial University, St. John's, NL, Canada.
J Bone Miner Metab. 2020 May;38(3):371-377. doi: 10.1007/s00774-019-01069-x. Epub 2020 Jan 1.
This study aimed to examine long-term persistence in new users of oral bisphosphonates in a population-wide cohort in Manitoba, Canada.
A longitudinal observational study was conducted using administrative health data characterizing long-term bisphosphonate persistence in those who started treatment between 1997 and 2018. Treatment discontinuation was evaluated using Kaplan-Meier methods. Cox regression was used to examine associations between discontinuation and osteoporosis diagnosis, previous fractures, and age. A sub-analysis of users with FRAX scores examined the relationship between 10-year fracture risk estimations and discontinuation.
Of 42,249 new bisphosphonate users, median age was 71 years, with 88.6% being female. Median duration of bisphosphonate use was 0.95 years (IQR 0.25, 3.9 years). Overall, 47.9% of incident users persisted up to 1 year, 25.0% persisted up to 3 years, and 14.1% up to 5 years. Presence of an indication for bisphosphonate use was associated with decreased discontinuation risk. Persistence generally increased with age. Having a BMD test performed was a predictor of lower discontinuation. The strongest predictor was having an osteoporosis diagnosis [HR for discontinuation = 0.68 (95% CI 0.66, 0.70)]. In users with FRAX scores (n = 14,114), moderate-risk [HR = 0.86 (95% CI 0.77, 0.96)] and high-risk users [HR = 0.77 (95% CI 0.69, 0.85)] were less likely to discontinue compared to lower-risk users.
A rapid decline in bisphosphonate persistence was shown. Almost half of users would not be expected to achieve clinically relevant benefits with a persistence of less than 1 year. Allowing informed choice in high-risk patients may be the best way to focus on those likely to benefit and persist with treatment.
本研究旨在考察加拿大马尼托巴省一个人群中口服双膦酸盐新使用者的长期持续用药情况。
采用纵向观察性研究，利用健康管理数据描述了 1997 年至 2018 年期间开始治疗的患者的长期双膦酸盐持续用药情况。采用 Kaplan-Meier 方法评估停药情况。采用 Cox 回归分析评估骨质疏松症诊断、既往骨折和年龄与停药的关系。对 FRAX 评分使用者进行亚组分析，探讨 10 年骨折风险估计值与停药的关系。
在 42249 名新的双膦酸盐使用者中，中位年龄为 71 岁，88.6%为女性。双膦酸盐使用的中位持续时间为 0.95 年（IQR 0.25，3.9 年）。总体而言，47.9%的新使用者在 1 年内持续用药，25.0%在 3 年内持续用药，14.1%在 5 年内持续用药。有双膦酸盐使用适应证与降低停药风险相关。随着年龄的增长，持续用药的比例逐渐增加。进行骨密度测试是预测较低停药率的指标。最强的预测指标是骨质疏松症诊断[停药风险比（HR）=0.68（95%置信区间 0.66，0.70）]。在有 FRAX 评分的使用者（n=14114）中，中危[HR=0.86（95%置信区间 0.77，0.96）]和高危[HR=0.77（95%置信区间 0.69，0.85）]患者较低危患者停药的可能性较低。
研究表明双膦酸盐的持续用药率迅速下降。不到一半的患者在 1 年的持续用药时间内不太可能获得临床相关的益处。在高危患者中允许知情选择可能是专注于那些可能受益和持续治疗的最佳方法。
