Castelnovo Giovanni, Gerlach Oliver, Freedman Mark S, Bergmann Arnfin, Sinay Vladimiro, Castillo-Triviño Tamara, Kong George, Koster Thijs, Williams Heather, Gafson Arie R, Killestein Joep
Service de Neurologie, CHU Caremeau, Nimes, France.
Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
CNS Drugs. 2021 Sep;35(9):1009-1022. doi: 10.1007/s40263-021-00840-x. Epub 2021 Jul 28.
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.
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.
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.
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.
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.
ClinicalTrials.gov: NCT01480063.
缓释氨吡啶（PR - FAM）10毫克片剂，每日两次，是唯一被批准用于改善成年多发性硬化症（MS）患者行走能力的药物治疗方法。LIBERATE评估了PR - FAM在现实世界中的安全性/有效性。
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65岁及以上患者和已有心血管危险因素的患者）中收集更多安全性数据，包括癫痫发作和其他感兴趣的不良事件（AE）的发生率。其他目标包括服用PR - FAM期间患者报告的MS对身体和心理影响的评估随时间的变化，以及医生报告的服用PR - FAM的MS患者行走能力评估随时间的变化。
招募新开具PR - FAM处方的MS患者（201个地点，13个国家）。在入组时至12个月期间收集人口统计学/安全性数据。评估医生评定的行走能力临床总体改善印象（CGI - I）评分和多发性硬化症影响量表 - 29（MSIS - 29）。
安全性分析纳入4646例患者，暴露时间为3534.8患者年；年龄中位数（范围）为52.6（21 - 85）岁，87.3%小于65岁，女性占65.7%。2448例（52.7%）患者报告了治疗中出现的不良事件（TEAE），279例（6.0%）患者报告了严重TEAE，其中37例（<1%）经历了被认为与PR - FAM相关的治疗中出现的严重不良事件（TESAEs）。1799例（38.7%）患者出现了特别感兴趣的不良事件（AESI），128例（2.8%）患者出现了严重AESI。17例（<1%）患者经历了实际癫痫发作事件。总体而言，1158例（24.9%）患者因缺乏疗效而停药。在12个月时，与停药患者相比，继续治疗的患者在行走能力的CGI - I方面从基线改善的比例更高（61%对11%；p < 0.001）。与停药患者相比，接受12个月治疗的患者的MSIS - 29身体影响评分有显著改善（从基线到12个月的平均变化：-9.99对-0.34分；p < 0.001）。MSIS - 29心理影响方面的结果相似。
在这项现实世界研究中未发现新的安全问题，表明常规风险最小化措施是有效的。PR - FAM治疗12个月后的CGI - I和MSIS - 29评分显示出与先前报告一致的临床益处。
ClinicalTrials.gov：NCT01480063。
