The University of Texas at Austin, 2409 University Ave., STOP A1930, Austin, TX 78712-1120.
J Manag Care Spec Pharm. 2014 Jul;20(7):657-67. doi: 10.18553/jmcp.2014.20.7.657.
BACKGROUND: Adalimumab (Humira [ADA]), etanercept (Enbrel [ETN]), and infliximab (Remicade [IFX]) are tumor necrosis factor (TNF) inhibitors indicated for the treatment of a variety of disorders. While their effectiveness has not been directly compared in a clinical trial, results from the majority of the indirect treatment comparisons suggest comparable efficacy and safety profiles. However, these TNF inhibitor agents differ in administration method and dosing flexibility, which may result in differences in medication use profiles (e.g., adherence, persistence, discontinuation, dose escalation, and switching to a new biologic rheumatoid arthritis drug) and effectiveness in clinical practice. OBJECTIVE: To estimate the effectiveness of ADA, ETN, and IFX in patients with rheumatoid arthritis (RA) using a validated, claims-based algorithm designed for large retrospective databases. METHODS: Adult (aged 18-63 years) patients diagnosed with RA, and receiving ADA, ETN, or IFX, and insured by Texas Medicaid were included. The index date was the date of the first prescription claim for ADA or ETN or infusion record for IFX with no claim or infusion record of a biologic drug in the preceding 6 months (i.e., biologic naïve). The study time frame was from July 2003 to August 2011, and prescription and medical claims for each subject were analyzed over an 18-month period (6 months pre- and 12 months post-index). Based on a RA medication effectiveness algorithm (Curtis et al. 2011), a RA medication was classified as effective if each of the following 6 criteria were met: (1) high medication adherence (i.e., medication possession ratio [MPR] ≥ 80%, defined as the sum of days' supply for all fills or infusions divided by the number of days in the study period); (2) no switching to (or addition of) new biologic RA drugs; (3) no addition of new nonbiologic RA drugs; (4) no increase in dose or frequency of administration of the RA medication currently evaluated; (5) no more than 1 glucocorticoid (GC) joint injection; and (6) no increase in dose of a concurrent oral GC. Propensity score (PS) matching was employed, and paired tests (i.e., McNemar's) and multivariate conditional logistic regression analysis were used to compare groups. Demographic (i.e., age, gender, race) and clinical (i.e., use of nonbiologic disease-modifying antirheumatic drugs [DMARDs], pain medication use, GC medication use, RA-related and non-RA-related health care visits [i.e., ambulatory and inpatient visits], number of nonstudy RA medications, and comorbidity index) characteristics, including total health care utilization cost at baseline, served as study covariates. RESULTS: After PS matching, 822 patients (n = 274 per group) were included. The majority of the sample (69.2%) was between 45-63 years, female (88%), and Hispanic (53.7%). Results for each TNF inhibitor differed significantly for 2 of the 6 effectiveness criteria (i.e., medication adherence and dose escalation). A significantly higher proportion of patients on IFX were adherent compared with patients on ETN or ADA (38.3% vs. 16.4% and 21.2%, P less than 0.0001 for both). Adherence rates between ETN and ADA were not significantly different. A significantly higher (P less than 0.0001) proportion of patients on ETN had no dose escalation compared with patients on ADA or IFX (98.2% vs. 88.7% and 80.3%, P less than 0.0001). Dose escalation rate was also significantly lower (P = 0.0106) for ADA compared with IFX. The multivariate conditional logistic regression analysis indicated no significant difference in overall effectiveness using the claims-based algorithm among the 3 TNF inhibitors nor any significant relationship between effectiveness and the study covariates. CONCLUSION: The study results suggest that when using a medication effectiveness algorithm, IFX, ETN, and ADA have comparable effectiveness in patients with RA. Patient adherence to therapy may be higher if given IFX, and patients who receive ETN are less likely to have a dose escalation.
背景:阿达木单抗(修美乐[ADA])、依那西普(恩利[ETN])和英夫利昔单抗(类克[IFX])是用于治疗多种疾病的肿瘤坏死因子(TNF)抑制剂。虽然它们的疗效尚未在临床试验中直接比较,但大多数间接治疗比较的结果表明,它们具有相似的疗效和安全性。然而,这些 TNF 抑制剂在给药方式和剂量灵活性方面存在差异,这可能导致药物使用模式(如依从性、持续性、停药、剂量升级和转换为新的生物类风湿关节炎药物)和在临床实践中的有效性存在差异。 目的:使用经过验证的、基于索赔的算法估计类风湿关节炎(RA)患者中 ADA、ETN 和 IFX 的疗效,该算法专为大型回顾性数据库设计。 方法:纳入接受 ADA、ETN 或 IFX 治疗且有德州医疗补助保险的成年(年龄 18-63 岁)RA 患者。索引日期为首次开具 ADA 或 ETN 处方或 IFX 输注记录的日期,此前 6 个月内无生物药物的处方或输注记录(即生物药物初治)。研究时间范围为 2003 年 7 月至 2011 年 8 月,对每位受试者的处方和医疗索赔进行了 18 个月的分析(6 个月的预索引期和 12 个月的后索引期)。根据 RA 药物疗效算法(Curtis 等人,2011 年),如果满足以下 6 个标准中的每一个,则将 RA 药物分类为有效:(1)高药物依从性(即 MPR≥80%,定义为所有配药或输注的天数之和除以研究期间的天数);(2)未转换(或添加)新的生物 RA 药物;(3)未添加新的非生物 RA 药物;(4)当前评估的 RA 药物剂量或频率未增加;(5)不超过 1 次关节内糖皮质激素(GC)注射;(6)未增加同时使用的口服 GC 的剂量。采用倾向评分(PS)匹配,并使用配对检验(即 McNemar's 检验)和多变量条件逻辑回归分析比较组间差异。人口统计学(即年龄、性别、种族)和临床(即使用非生物疾病修饰抗风湿药物[DMARDs]、疼痛药物使用、GC 药物使用、RA 相关和非 RA 相关的医疗保健就诊[即门诊和住院就诊]、非研究 RA 药物的数量和合并症指数)特征,包括基线时的总医疗保健利用成本,作为研究协变量。 结果:经过 PS 匹配后,纳入了 822 名患者(每组 n=274 名)。样本的大多数(69.2%)年龄在 45-63 岁之间,女性(88%)和西班牙裔(53.7%)。对于 6 个疗效标准中的 2 个标准(即药物依从性和剂量升级),每个 TNF 抑制剂的结果差异显著。与 ETN 或 ADA 相比,IFX 治疗的患者依从性显著更高(38.3%比 16.4%和 21.2%,P<0.0001)。ETN 和 ADA 之间的依从率没有显著差异。与 ADA 或 IFX 相比,ETN 治疗的患者无剂量升级的比例显著更高(98.2%比 88.7%和 80.3%,P<0.0001)。ADA 的剂量升级率也显著较低(P=0.0106)。多变量条件逻辑回归分析表明,在基于索赔的算法中,三种 TNF 抑制剂的总体疗效没有显著差异,疗效与研究协变量之间也没有显著关系。 结论:研究结果表明,使用药物疗效算法时,IFX、ETN 和 ADA 在 RA 患者中的疗效相当。如果给予 IFX,患者的治疗依从性可能更高,而接受 ETN 的患者剂量升级的可能性更低。
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