Background

Prolonged-release fampridine (PR-FAM) 10-mg tablet twice daily is the only approved pharmacological treatment for improvement of walking ability in adults with multiple sclerosis (MS). LIBERATE assessed the safety/effectiveness of PR-FAM in the real-world.

Objectives

The aim of this study was to collect additional safety data, including the incidence rate of seizures and other adverse events (AEs) of interest, from patients with MS taking PR-FAM in routine clinical practice (including patients aged ≥ 65 years and those with pre-existing cardiovascular risk factors). Other objectives included change over time in patient-reported evaluation of physical and psychological impact of MS while taking PR-FAM, and change over time in physician-reported assessment of walking ability in MS patients taking PR-FAM.

Methods

Patients with MS newly prescribed PR-FAM were recruited (201 sites, 13 countries). Demographic/safety data were collected at enrolment through 12 months. Physician-rated Clinical Global Impression of Improvement (CGI-I) scores for walking ability, and Multiple Sclerosis Impact Scale-29 (MSIS-29) were assessed.

Results

Safety analysis included 4646 patients with 3534.8 patient-years of exposure; median (range) age, 52.6 (21–85) years, 87.3% < 65 years, and 65.7% women. Treatment-emergent AEs (TEAEs) were reported in 2448 (52.7%) patients, and serious TEAEs were reported in 279 (6.0%) patients, of whom 37 (< 1%) experienced treatment-emergent serious AEs (TESAEs) considered related to PR-FAM. AEs of special interest (AESI) occurred in 1799 (38.7%) patients, and serious AESI in 128 (2.8%) patients. Seventeen (< 1%) patients experienced actual events of seizure. Overall, 1158 (24.9%) patients discontinued treatment due to lack of efficacy. At 12 months, a greater proportion of patients on-treatment had improvement from baseline in CGI-I for walking ability versus those who discontinued (61% vs. 11%; p < 0.001). MSIS-29 physical impact score improved significantly for patients on-treatment for 12 months versus those who discontinued (mean change, baseline to 12 months: − 9.99 vs. − 0.34 points; p < 0.001). Results were similar for MSIS-29 psychological impact.

Conclusion

No new safety concerns were identified in this real-world study, suggesting that routine risk-minimization measures are effective. CGI-I and MSIS-29 scores after 12 months treatment with PR-FAM treatment show clinical benefits consistent with those previously reported.

Trial Registration

ClinicalTrials.gov: NCT01480063.

中文翻译：

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多发性硬化症患者在常规临床实践中长期释放氨吡啶治疗的安全性、患者报告的幸福感和医生报告的步行能力评估：LIBERATE 研究的结果

背景

缓释氨吡啶 (PR-FAM) 10 毫克片剂，每日两次，是唯一获批用于改善多发性硬化症 (MS) 成人步行能力的药物治疗。LIBERATE 评估了 PR-FAM 在现实世界中的安全性/有效性。

目标

本研究的目的是从常规临床实践中服用 PR-FAM 的 MS 患者（包括年龄 ≥ 65 岁的患者和患有预先存在的心血管危险因素）。其他目标包括患者报告的在服用 PR-FAM 时对 MS 的身体和心理影响的评估随时间的变化，以及医生报告的对服用 PR-FAM 的 MS 患者步行能力的评估随时间的变化。

方法

招募了 MS 新处方 PR-FAM 的患者（201 个地点，13 个国家）。在 12 个月内收集人口统计/安全数据。评估了步行能力和多发性硬化症影响量表 29 (MSIS-29) 的医师评定的临床整体改善印象 (CGI-I) 评分。

结果

安全性分析包括 4646 名患者，暴露时间为 3534.8 患者年；中位（范围）年龄，52.6（21-85）岁，87.3% < 65 岁，65.7% 为女性。2448 名 (52.7%) 患者报告了治疗紧急 AE (TEAE)，279 名 (6.0%) 患者报告了严重 TEAE，其中 37 名 (< 1%) 经历了被认为与治疗相关的治疗紧急严重 AE (TEAE)公关-FAM。1799 例 (38.7%) 患者发生了特别关注的 AE (AESI)，128 例 (2.8%) 患者发生了严重的 AESI。17 名 (< 1%) 患者经历了实际的癫痫发作事件。总体而言，1158 名 (24.9%) 患者因缺乏疗效而停止治疗。在 12 个月时，与停止治疗的患者相比，更大比例的接受治疗的患者的 CGI-I 行走能力较基线有所改善（61% 对 11%；p < 0.001)。与停止治疗的患者相比，接受治疗 12 个月的患者的 MSIS-29 身体影响评分显着改善（平均变化，基线至 12 个月：- 9.99 与 - 0.34 分；p  < 0.001）。MSIS-29 心理影响的结果相似。

结论

在这项真实世界的研究中没有发现新的安全问题，这表明常规的风险最小化措施是有效的。用 PR-FAM 治疗 12 个月后的 CGI-I 和 MSIS-29 评分显示出与先前报道的一致的临床益处。

试用注册

ClinicalTrials.gov：NCT01480063。