Background

Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited.

Objective

The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting.

Methods

We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated.

Results

Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6–41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy.

Conclusions

Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.

中文翻译：

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富马酸二甲酯治疗多发性硬化症的三年有效性：前瞻性多中心真实世界研究

背景

富马酸二甲酯 (DMF) 在 III 期研究中已证明有效。然而，现实世界的数据仍然有限。

客观的

本研究的目的是描述接受 DMF 的患者的概况，并评估 DMF 在西班牙人群中在复发、残疾进展、磁共振成像活动和 NEDA（无证据疾病活动）-3 状态方面的有效性。现实世界的设定。

方法

我们对 2014 年至 2019 年间在西班牙开始使用 DMF 的患者进行了一项多中心前瞻性研究。考虑了三个亚组：天真、因无效而改用 DMF、因不良反应改用 DMF。评估了 DMF 对临床和放射学测量的影响。

结果

在 886 名患者中，25.3% 是初治患者，28.8% 是因为不良反应，45.9% 是因为无效。中位随访时间为 38.9（四分位距 22.6-41.8）个月。12、24 和 36 个月的年化复发率分别为 0.15、0.10 和 0.10，77.7% 的患者在第 42 个月无复发。在 12、24 和 42 个月时，分别为 96.1%、87.4% 和 79.7%患者分别无进展。在 12、24 和 36 个月时，T1 钆增强 (T1Gd+) 病变的数量分别为 0.19、0.14 和 0.18。49.8% 的患者在第 42 个月时保持 NEDA-3 状态。复发与前一年较高的年化复发率相关（风险比 1.34，p < 0.001）和无效转换与初始组（风险比 1.76，p= 0.003）。较高的基线扩展残疾状态量表评分与残疾进展（风险比 1.15，p = 0.003）和更多 T1Gd+ 病变（风险比 1.07，p < 0.001）与放射学进展相关。更高的基线扩展残疾状态量表评分、更多的 T1Gd+ 病变以及由于无效（相对于不良事件）而转换都是失去 NEDA-3 状态的风险因素。29.9% 的患者停用 DMF，13.5% 的患者因无效而停用。

结论

我们的研究结果证实了 DMF 在真实世界环境中对多发性硬化症的临床和放射学活动的持续有效性，无论是在初治患者还是从其他多发性硬化症治疗转换的患者中。