Real-World Utilization Patterns, Safety, and Efficacy of Tafamidis in Patients With Hereditary Transthyretin Amyloidosis in Japan

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental Pub Date : 2025-01-01 DOI:10.1016/j.curtheres.2025.100793

Hiroaki Konishi PharmD , Hajime Abe MD, PhD , Noriko Matsumoto , Yutaka Endo , Yoshiki Sekijima MD, PhD , Mitsuharu Ueda MD, PhD , Yukio Ando MD, PhD

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引用次数: 0

Abstract

Purpose

Patients with hereditary transthyretin (ATTRv) amyloidosis experience progressive degeneration of the somatic and peripheral nervous system that can impair ambulation, autonomy, and quality of life (QOL). Tafamidis meglumine (tafamidis) is the first pharmacotherapy approved to slow the progression of peripheral neurological impairment in ATTRv amyloidosis and was well tolerated and efficacious in clinical trials; however, longer-term safety in Japanese patients with ATTRv amyloidosis has not been fully elucidated. Consequently, the present study was conducted to understand the safety and efficacy of long-term use (up to 156 weeks) of tafamidis meglumine under postmarketing conditions in Japan.

Methods

This single-arm observational study (conducted from November 2013 to May 2021) included all patients prescribed tafamidis (20 mg/day) for the treatment of ATTRv amyloidosis in routine clinical practice. The observation period was 156 weeks (3 years) following tafamidis initiation (78 weeks [1.5 years] for patients who initiated treatment after May 2018). The outcomes of interest were clinical characteristics of patients, tafamidis utilization patterns, adverse drug reactions (ADRs), serious ADRs (safety analysis set), and efficacy (Neuropathy Impairment Score–Lower Limbs [NIS-LL] score, total QOL [TQOL] score, modified body mass index [mBMI], and ambulatory status; efficacy analysis set).

Findings

A total of 400 and 397 patients were included in the safety and efficacy analysis sets, respectively. The mean ± standard deviation (SD) age was 61.5 ± 15.0 years, 65.5% were male, 57.3% were aged ≥50 years at disease onset, 71.0% were from nonendemic areas, and 10.3% had Karnofsky Performance Status 40 to 10. A total of 212 (53.0%) patients were treated with tafamidis for >156 weeks (mean ± SD treatment duration: 120.8 ± 56.4 weeks) and 145 (36.3%) patients discontinued the study, with the reasons for discontinuation (duplicate) being adverse events (n = 46), hospital transfer (n = 33), loss to follow-up (n = 15), insufficient clinical response (n = 9), and others (n = 62). ADRs and serious ADRs were reported in 58 (14.5%) and 12 (3.0%) patients, respectively. In the efficacy analysis set, NIS-LL score, TQOL score, mBMI, and ambulatory status after 156 weeks of treatment were comparable to those reported prior to tafamidis initiation.

Implications

The findings of this study indicate that late-onset cases of ATTRv amyloidosis and those that originate from nonendemic areas may be more prevalent in Japan than historically believed. The safety profile of tafamidis was largely consistent with that obtained from previous research, and no new safety concerns were identified. The efficacy of tafamidis was also demonstrated in the real-world clinical setting.

Clinical trial registration

NCT02146378 (ClinicalTrials.gov).

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日本遗传性甲状腺转蛋白淀粉样变性患者使用他法米地的现实世界模式、安全性和有效性

目的遗传性甲状腺转蛋白（ATTRv）淀粉样变患者会经历躯体和周围神经系统的进行性变性，从而损害行动能力、自主性和生活质量（QOL）。Tafamidis meglumine （Tafamidis）是首个被批准用于减缓ATTRv淀粉样变性患者周围神经损伤进展的药物疗法，在临床试验中耐受性良好且有效；然而，日本ATTRv淀粉样变患者的长期安全性尚未完全阐明。因此，本研究旨在了解在日本上市后条件下长期使用（长达156周）他法底司megumine的安全性和有效性。方法：该单组观察性研究（2013年11月至2021年5月）纳入了所有在常规临床实践中使用他法非地（20 mg/天）治疗ATTRv淀粉样变的患者。他法非地开始治疗后的观察期为156周（3年）（2018年5月后开始治疗的患者为78周（1.5年））。关注的结局是患者的临床特征、他非他汀的使用模式、药物不良反应（adr）、严重adr（安全性分析集）和疗效(神经损伤评分-下肢评分、总生活质量评分、修正体重指数（mBMI）和门诊状态；疗效分析集)。结果分别有400例和397例患者被纳入安全性和有效性分析集。平均±标准差（SD）年龄为61.5 ± 15.0岁，65.5%为男性，57.3%发病年龄≥50岁，71.0%来自非疫区，10.3%为Karnofsky Performance Status 40 ~ 10。共有212例(53.0%)患者接受tafamidis祝辞,156周(120.8±SD治疗持续时间: ± 56.4周)和145年(36.3%)的患者停止了研究,与中止的原因(复制)不良事件(n = 46),医院转移(n = 33),追踪损失(n = 15),临床反应不足(n = 9),和其他(n = 62)。不良反应58例（14.5%），严重不良反应12例（3.0%）。在疗效分析集中，治疗156周后的NIS-LL评分、TQOL评分、mBMI和门诊状态与他法非地开始治疗前的报告相当。本研究结果表明，迟发性ATTRv淀粉样变病例和来自非流行地区的病例在日本可能比历史上认为的更为普遍。塔法米底裤的安全性与以前的研究结果基本一致，没有发现新的安全问题。他法米底斯的疗效也在现实世界的临床环境中得到证实。临床试验注册nct02146378 （ClinicalTrials.gov）。

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来源期刊

Current Therapeutic Research-clinical and Experimental 医学-药学

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

3 months

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