Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
Adv Ther. 2021 Jan;38(1):337-349. doi: 10.1007/s12325-020-01537-1. Epub 2020 Oct 28.
Clinical guidelines recommend levothyroxine as the standard of care for hypothyroidism and that patients should be treated with a consistent preparation of synthetic levothyroxine without switching among formulations. This study examines the likelihoods of negative clinical outcomes between continuous users of Synthroid (AbbVie, Inc.) and patients who switch from Synthroid to an alternative formulation of levothyroxine.
This retrospective cohort analysis utilized data from Optum Clinformatics™ DataMart covering May 1, 2000 to March 30, 2016. After 6 months of consistent use of Synthroid, patients were categorized as continuous users or as switchers (by filling a prescription for an alternative formulation). Key outcomes included the likelihood of a thyroid-stimulating hormone (TSH) laboratory value out of a guideline recommended range and/or an adverse clinical composite endpoint identified by ICD codes in the patient's claims data over the following 2 years for any of the following: chronic kidney disease, depression, fatigue, heart failure, hyperlipidemia, hypertension, or obesity. Individual components of the composite endpoint were also examined. Outcomes were analyzed using multivariable logistic models on propensity score matched cohorts. Analyses controlled for patient characteristics using SAS 9.4 software. Chi-square and t tests were employed and P < 0.05 was pre-specified as statistically significant.
Propensity score matching resulted in a sample of 9925 continuous users and 9925 switchers. Switchers were significantly more likely than continuers to have a TSH laboratory value out-of-range in the post-period [odds ratio (OR) 1.15; 95% confidence interval (CI) (1.08-1.23)]. Switchers were also more likely to have the composite clinical endpoint [OR 1.23; CI (1.12-1.37)] and to have individual diagnoses of chronic kidney disease, depression, fatigue, hypertension, or obesity in the post-period.
Results of this large retrospective study over an extended time horizon support clinical guideline recommendations that switching among alternative formulations of synthetic levothyroxine should generally be avoided. Continuous use of Synthroid was associated with a significantly higher likelihood of maintaining the TSH laboratory value within a guideline recommended range and a significantly lower likelihood of being diagnosed with adverse clinical outcomes.
临床指南推荐左甲状腺素为治疗甲状腺功能减退症的标准治疗方法，并建议患者使用一致的合成左甲状腺素制剂，避免在不同制剂之间转换。本研究旨在比较连续使用 Synthroid（AbbVie，Inc.）的患者与从 Synthroid 转换为其他左甲状腺素制剂的患者之间发生不良临床结局的可能性。
本回顾性队列分析使用了来自 Optum Clinformatics™ DataMart 的数据，时间范围为 2000 年 5 月 1 日至 2016 年 3 月 30 日。在连续使用 Synthroid 6 个月后，根据患者是否开具了替代制剂的处方，将其分为连续使用者或转换者。主要结局包括在接下来的 2 年内，使用甲状腺刺激激素（TSH）实验室值是否超出指南推荐范围，以及患者索赔数据中通过 ICD 编码识别出的任何以下不良临床复合终点的可能性：慢性肾脏病、抑郁症、疲劳、心力衰竭、高血脂、高血压或肥胖症。还对复合终点的各个组成部分进行了检查。使用倾向评分匹配队列的多变量逻辑模型分析了结局。使用 SAS 9.4 软件对患者特征进行了控制。采用卡方检验和 t 检验，P<0.05 为统计学显著。
倾向评分匹配后，共纳入 9925 名连续使用者和 9925 名转换者。在随访期间，转换者的 TSH 实验室值超出范围的可能性明显高于连续使用者[比值比（OR）1.15；95%置信区间（CI）（1.08-1.23）]。转换者发生复合临床终点的可能性也更高[OR 1.23；CI（1.12-1.37）]，且在随访期间更有可能被诊断为慢性肾脏病、抑郁症、疲劳、高血压或肥胖症。
这项在较长时间范围内进行的大型回顾性研究的结果支持临床指南的建议，即在一般情况下，应避免在不同的合成左甲状腺素制剂之间转换。连续使用 Synthroid 与 TSH 实验室值保持在指南推荐范围内的可能性显著增加，以及与发生不良临床结局的可能性显著降低相关。
