Importance Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The difference in the association of these national strategies with clinical outcomes is unknown. Objective To investigate the association of national differences in disease-modifying treatment (DMT) strategies for RRMS with disability outcomes. Design, Setting, and Participants This cohort study used data on 4861 patients from the Danish and Swedish national multiple sclerosis (MS) registries from the date of index DMT initiation (between January 1, 2013, and December 31, 2016) until the last recorded visit at time of data extraction (October 2, 2019). Exposures All MS-specific DMTs initiated during the observation period were included in the analysis. Main Outcomes and Measures The primary study outcome was time to 24-week confirmed disability worsening. Secondary outcomes were 24-week confirmed disability improvement, milestone Expanded Disability Status Scale scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switching. Data were analyzed using inverse probability of treatment weighting-based models using a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the 2 countries. Results A total of 2700 patients from the Swedish MS registry (1867 women [69.2%]; mean [SD] age, 36.1 [9.5] years) and 2161 patients from the Danish MS registry (1472 women [68.1%]; mean [SD] age, 37.3 [9.4 years]) started a first DMT between 2013 and 2016, were included in the analysis, and were observed for a mean (SD) of 4.1 (1.5) years. A total of 1994 Danish patients (92.3%) initiated a low to moderately effective DMT (teriflunomide, 907 [42.0%]) and 165 (7.6%) initiated a highly effective DMT, whereas a total of 1769 Swedish patients (65.5%) initiated a low to moderately effective DMT (teriflunomide, 64 [2.4%]) and 931 (34.5%) initiated a highly effective DMT. The Swedish treatment strategy was associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (hazard ratio, 0.71; 95% CI, 0.57-0.90; P = .004). The Swedish treatment strategy was also associated with a 24% reduction in the rate of reaching an expanded disability status scale score of 3 (hazard ratio, 0.76; 95% CI, 0.60-0.97; P = .03) and a 25% reduction in the rate of reaching an expanded disability status scale score of 4 (hazard ratio, 0.75; 95% CI, 0.61-0.96; P = .01) relative to Danish patients. Conclusions and Relevance The findings of this study suggest that there is an association between differences in treatment strategies for RRMS and disability outcomes at a national level. Escalation of treatment efficacy was inferior to using more efficacious DMT as initial treatment.

中文翻译：

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复发缓解型多发性硬化症患者的治疗升级与立即开始高效治疗：来自 2 种不同国家战略的数据。

复发缓解型多发性硬化症 (RRMS) 的治疗策略在丹麦和瑞典之间存在显着差异。这些国家策略与临床结果之间的关联差异尚不清楚。目的 调查 RRMS 疾病改善治疗 (DMT) 策略的国家差异与残疾结果之间的关系。设计、设置和参与者 本队列研究使用了丹麦和瑞典国家多发性硬化症 (MS) 登记处的 4861 名患者的数据，从指数 DMT 开始之日（2013 年 1 月 1 日至 2016 年 12 月 31 日）到最后一次记录在数据提取时访问（2019 年 10 月 2 日）。暴露 在观察期间启动的所有 MS 特异性 DMT 都包括在分析中。主要结果和措施 主要研究结果是到 24 周确认残疾恶化的时间。次要结果是 24 周确认的残疾改善、里程碑式的扩展残疾状态量表评分为 3 和 4、年化复发率、首次复发时间和治疗转换。使用基于治疗加权的逆概率模型分析数据，使用倾向得分加权和校正两个国家在基线观察到的混杂因素不平衡的比较。结果 瑞典 MS 登记处共有 2700 名患者（1867 名女性 [69.2%]；平均 [SD] 年龄，36.1 [9.5] 岁）和丹麦 MS 登记处的 2161 名患者（1472 名女性 [68.1%]；平均 [SD] ] 年龄，37.3 [9.4 岁]）在 2013 年至 2016 年间开始第一次 DMT，被纳入分析，并观察到平均 (SD) 为 4。1 (1.5) 年。共有 1994 名丹麦患者（92.3%）开始了低效至中效 DMT（特立氟胺，907 [42.0%]），165 名（7.6%）开始了高效 DMT，而共有 1769 名瑞典患者（65.5%）开始了低至中等有效的 DMT（特立氟胺，64 [2.4%]）和 931（34.5%）启动了高效的 DMT。与丹麦治疗策略相比，瑞典治疗策略与基线后 24 周确认的残疾恶化率降低 29% 相关（风险比，0.71；95% CI，0.57-0.90；P = .004）。瑞典的治疗策略也与扩大残疾状态量表评分 3 分的比率降低 24% 相关（风险比，0.76；95% CI，0.60-0.97；P = . 03)，与丹麦患者相比，达到扩展残疾状态量表评分 4 分的比率降低了 25%（风险比，0.75；95% CI，0.61-0.96；P = .01）。结论和相关性 本研究的结果表明，RRMS 治疗策略的差异与国家层面的残疾结果之间存在关联。治疗效果的升级不如使用更有效的 DMT 作为初始治疗。