Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
Bristol-Myers Squibb Company, Princeton, NJ, USA.
Clin Ther. 2020 Nov;42(11):2136-2147.e3. doi: 10.1016/j.clinthera.2020.09.014. Epub 2020 Nov 5.
Although all disease-modifying therapies (DMTs) reduce risk of relapse in multiple sclerosis (MS), many factors, including route of administration, influence selection of first-line DMT. Knowledge of real-world treatment patterns and effectiveness in reducing relapses across DMTs is important to understanding factors influencing this choice. This study sought to describe treatment patterns and relapses among newly treated adults with MS and by DMT route of administration (oral, injectable, and infusion).
IBM MarketScan research databases were used to identify MS adults newly initiating DMTs (index event) from January 1, 2011-April 1, 2016, who had 12 months of continuous preindex and postindex medical and pharmacy benefits. Newly treated patients were those with ≥2 nondiagnostic claims with an International Classification of Diseases, Ninth Revision, Clinical Modification (340) or Tenth Revision, Clinical Modification (G35) code and no DMT prescription claims in the 12 months' preindex. Persistence and adherence were measured from index until the earliest of ≥60 days without DMT, switching DMTs, or end of follow-up. Relapses were defined using a validated claims-based algorithm and measured in the 12-month preindex and postindex periods. Regression analysis adjusting for patient characteristics and prior relapses was used to determine the association between DMT route of administration and odds of 12-month persistence, odds of postindex relapse, and number of postindex relapses.
Of 9378 newly treated MS patients meeting inclusion criteria; average age was 46.7 years, and 73.3% were female. Most patients initiated an injectable (65.5%) or oral (26.1%) DMT. Relapses decreased markedly from preindex to postindex (32.9%-24.0%), which was highest among oral users (35.8%-21.6%). Patients with no (vs ≥3) relapses preindex were more likely to be relapse free postindex (81.6% vs 31.4%). Nonpersistence (39.1% overall) was lowest among oral users (33.4%) and higher among those with versus without a postindex relapse (50.6% vs 35.5%). Patients initiating oral versus injectable agents were more likely to be persistent at 12 months (odds ratio [OR], 1.45; p < 0.0001) and less likely to relapse (OR, 0.75; p < 0.0001) postindex. Switches were uncommon (~10%) across cohorts. Preindex relapses were associated with increased odds of postindex relapses (OR, 1.73; p < 0.0001) but not with odds of persistence at 12 months.
The 12-month nonpersistence rate was high among all MS patients but lower among oral users. Oral users were also less likely to relapse postindex. Despite the effectiveness of DMTs in reducing relapses, the low persistence, lack of switching to a new DMT, and continued relapses highlight an unmet need in the MS treatment landscape.
虽然所有的疾病修正疗法（DMT）都能降低多发性硬化症（MS）的复发风险，但许多因素，包括给药途径，都会影响一线 DMT 的选择。了解在不同 DMT 中减少复发的真实世界治疗模式和有效性对于理解影响这种选择的因素非常重要。本研究旨在描述新治疗的 MS 成人的治疗模式和复发情况，并按 DMT 给药途径（口服、注射和输注）进行分类。
使用 IBM MarketScan 研究数据库，从 2011 年 1 月 1 日至 2016 年 4 月 1 日，确定新开始 DMT（索引事件）的 MS 成年人，他们在索引前和索引后 12 个月内均有连续的医疗和药房福利。新治疗的患者是指至少有 2 次无诊断性的索赔，其国际疾病分类，第九版修订版（340）或第十版修订版（G35）代码，并且在索引前的 12 个月内没有 DMT 处方索赔。从索引开始到 DMT 停止使用、更换 DMT 或随访结束的最早时间，至少有 60 天没有 DMT 的使用，即被定义为持续和依从。复发使用经过验证的基于索赔的算法进行定义，并在索引前和索引后 12 个月内进行测量。使用回归分析，调整患者特征和既往复发情况，以确定 DMT 给药途径与 12 个月的持续率、索引后复发的可能性以及索引后复发次数之间的关联。
在符合纳入标准的 9378 名新治疗的 MS 患者中；平均年龄为 46.7 岁，73.3%为女性。大多数患者开始使用注射剂（65.5%）或口服剂（26.1%）DMT。从索引前到索引后，复发明显减少（32.9%-24.0%），其中口服剂使用者的复发率最高（35.8%-21.6%）。索引前无（vs≥3）复发的患者更有可能在索引后无复发（81.6% vs 31.4%）。总体非持续性（39.1%）在口服剂使用者中最低（33.4%），而在有与无索引后复发的患者中更高（50.6% vs 35.5%）。与注射剂相比，开始使用口服剂的患者更有可能在 12 个月时保持持续状态（比值比[OR]，1.45；p<0.0001），并且不太可能在索引后复发（OR，0.75；p<0.0001）。各队列中换药的情况较为少见（约 10%）。索引前的复发与索引后复发的可能性增加（OR，1.73；p<0.0001）相关，但与 12 个月的持续率无关。
所有 MS 患者的 12 个月非持续性率较高，但口服剂使用者的非持续性率较低。口服剂使用者索引后复发的可能性也较低。尽管 DMT 能有效降低复发率，但低持续率、缺乏新 DMT 的转换以及持续复发，突显了 MS 治疗领域存在未满足的需求。
