1 Novartis Pharmaceuticals, East Hanover, New Jersey.
2 Consulting, Morristown, New Jersey.
J Manag Care Spec Pharm. 2017 Aug;23(8):844-852. doi: 10.18553/jmcp.2017.23.8.844.
Disease-modifying therapies (DMTs) are indicated to reduce relapse rates and slow disease progression for relapsing-remitting multiple sclerosis (MS) patients when taken as prescribed. Nonadherence or non-persistence in the real-world setting can lead to greater risk for negative clinical outcomes. Although previous research has demonstrated greater adherence and persistence to oral DMTs compared with injectable DMTs, comparisons among oral DMTs are lacking.
To compare adherence, persistence, and time to discontinuation among MS patients newly prescribed the oral DMTs fingolimod, dimethyl fumarate, or teriflunomide.
This retrospective study used MarketScan Commercial and Medicare Supplemental claims databases. MS patients with ≥ 1 claim for specified DMTs from April 1, 2013, to June 30, 2013, were identified. The index drug was defined as the first oral DMT within this period. To capture patients newly initiating index DMTs, patients could not have a claim for their index drugs in the previous 12 months. Baseline characteristics were described for patients in each treatment cohort. Adherence, as measured by medication possession ratio (MPR) and proportion of days covered (PDC); persistence (30-day gap allowed); and time to discontinuation over a 12-month follow-up period were compared across treatment cohorts. Adjusted logistic regression models were used to examine adherence, and Cox regression models estimated risk of discontinuation.
1,498 patients newly initiated oral DMTs and met study inclusion criteria: fingolimod (n = 185), dimethyl fumarate (n = 1,160), and teriflunomide (n = 143). Patients were similar across most baseline characteristics, including region, relapse history, and health care resource utilization. Statistically significant differences were observed across the treatment cohorts for age, gender, previous injectable/infused DMT use, and comorbidities. Adherence and time to discontinuation were adjusted for age, gender, region, previous oral and injectable/infused DMT use, relapse history, and Charlson Comorbidity Index score. Relative to fingolimod patients, dimethyl fumarate and teriflunomide patients were significantly less likely to have an MPR ≥ 80% (OR = 0.18; 95% CI = 0.09-0.36; P < 0.001 and OR = 0.19; 95% CI = 0.08-0.42; P < 0.001, respectively). Similarly, relative to fingolimod patients, dimethyl fumarate and teriflunomide patients were significantly less likely to have PDC ≥ 80% (OR = 0.47; 95% CI = 0.33-0.67; P < 0.001 and OR = 0.37; 95% CI = 0.23-0.59; P < 0.001, respectively). Additionally, the HR for discontinuation was about 2 times greater for dimethyl fumarate (HR = 1.93; 95% CI = 1.44-2.59; P < 0.001) and teriflunomide patients (HR = 2.27; 95% CI = 1.57-3.28; P < 0.001) compared with fingolimod.
In a real-world setting, patients taking fingolimod had better adherence and persistence compared with patients taking other oral DMTs over 12 months. Coupled with clinical factors, medication adherence and persistence should be important considerations when determining coverage decisions for MS patients.
This research was funded by Novartis Pharmaceuticals. Johnson, Lin, Ko, and Herrera are employed by Novartis Pharmaceuticals and own Novartis stock. Huanxue Zhou is employed by KMK Consulting, which provides consulting services to Novartis. Study concept and design were contributed by Johnson, Lin, Ko, and Herrera. Zhou collected the data, and data interpretation was performed by Johnson, Lin, Ko, and Herrera. All authors were involved in manuscript revision. The abstract for this study was presented at the AMCP Nexus 2015; October 26-29, 2015; Orlando, Florida.
对于复发缓解型多发性硬化症(MS)患者,疾病修正疗法(DMT)在按规定服用时可降低复发率并减缓疾病进展。在真实环境中不遵守或不坚持治疗可能会导致更严重的临床后果。尽管先前的研究表明与注射用 DMT 相比,口服 DMT 的依从性和持久性更高,但缺乏口服 DMT 之间的比较。
比较新处方口服 DMTs(fingolimod、dimethyl fumarate 或 teriflunomide)的 MS 患者的依从性、持久性和停药时间。
这项回顾性研究使用了 MarketScan 商业和医疗保险补充数据库。从 2013 年 4 月 1 日至 2013 年 6 月 30 日,确定了至少有一次指定 DMT 治疗的 MS 患者。索引药物被定义为在此期间的第一种口服 DMT。为了捕获新开始使用索引 DMT 的患者,患者在过去 12 个月内不得有索引药物的索赔。描述了每个治疗队列中患者的基线特征。通过药物占有比例(MPR)和覆盖天数比例(PDC)衡量依从性;30 天的允许间隔期;在 12 个月的随访期间,比较了不同治疗队列的停药时间。调整后的逻辑回归模型用于检查依从性,Cox 回归模型估计停药风险。
1498 名新开始口服 DMT 且符合研究纳入标准的患者:fingolimod(n=185)、dimethyl fumarate(n=1160)和 teriflunomide(n=143)。患者在大多数基线特征方面相似,包括地区、复发史和医疗资源利用情况。在治疗队列之间观察到显著的差异,包括年龄、性别、既往注射/输注 DMT 使用情况和合并症。对年龄、性别、地区、既往口服和注射/输注 DMT 使用情况、复发史和 Charlson 合并症指数评分进行了调整,以调整依从性和停药时间。与 fingolimod 患者相比,dimethyl fumarate 和 teriflunomide 患者的 MPR≥80%的可能性显著降低(OR=0.18;95%CI=0.09-0.36;P<0.001 和 OR=0.19;95%CI=0.08-0.42;P<0.001)。同样,与 fingolimod 患者相比,dimethyl fumarate 和 teriflunomide 患者的 PDC≥80%的可能性显著降低(OR=0.47;95%CI=0.33-0.67;P<0.001 和 OR=0.37;95%CI=0.23-0.59;P<0.001)。此外,dimethyl fumarate(HR=1.93;95%CI=1.44-2.59;P<0.001)和 teriflunomide 患者(HR=2.27;95%CI=1.57-3.28;P<0.001)的停药风险大约是 fingolimod 的两倍。
在真实环境中,与服用其他口服 DMT 的患者相比,服用 fingolimod 的患者在 12 个月内的依从性和持久性更好。结合临床因素,MS 患者的药物依从性和持久性应是决定覆盖范围决策的重要考虑因素。
这项研究由诺华制药公司资助。Johnson、Lin、Ko 和 Herrera 受雇于诺华制药公司并拥有诺华制药公司的股票。Huanxue Zhou 受雇于 KMK 咨询公司,该公司为诺华制药公司提供咨询服务。Johnson、Lin、Ko 和 Herrera 提出了研究概念和设计。Zhou 收集了数据,Johnson、Lin、Ko 和 Herrera 进行了数据解释。所有作者都参与了修改手稿。这项研究的摘要在 2015 年 10 月 26 日至 29 日举行的 AMCP Nexus 2015 年会上提出;佛罗里达州奥兰多。