Background: Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted.

Methods: Safety data from all sponsored, completed, or ongoing, Phase 2/3 studies of tafamidis in ATTR-PN patients as of 3 January 2017 were pooled. Also assessed were safety data from the ongoing Transthyretin Amyloidosis Outcomes Survey (THAOS) as of 3 January 2017 and post-marketing surveillance reports as of 31 March 2017.

Results: There were 137 patients in Phase 2/3 studies (mean duration of tafamidis exposure, 44.2 months), with 134 (97.8%) experiencing ≥1 treatment-emergent adverse event (TEAE) and 46 (33.6%) ≥1 treatment-emergent serious adverse event (TESAE). The most common TEAEs were diarrhoea (26.3%), urinary tract infection (UTI; 25.5%) and influenza (21.2%). In THAOS, 661 subjects had tafamidis exposure (mean duration, 27.6 months), with 250 (37.8%) experiencing ≥1 TEAE and 96 (14.5%) ≥1 TESAE. The most common TEAE was UTI (6.1%). Post-marketing surveillance reports generally reflected the known safety profile of tafamidis.

Conclusions: This analysis did not reveal any significant new safety findings; tafamidis was generally safe and well tolerated in ATTR-PN patients.

Trial registration: ClinicalTrials.gov identifier: NCT00409175.

Trial registration: ClinicalTrials.gov identifier: NCT00791492.

Trial registration: ClinicalTrials.gov identifier: NCT00630864.

Trial registration: ClinicalTrials.gov identifier: NCT01435655.

Trial registration: ClinicalTrials.gov identifier: NCT00925002.

Trial registration: ClinicalTrials.gov identifier: NCT00628745.

背景：塔法米迪已在40多个国家/地区获得批准，可延缓转甲状腺素蛋白淀粉样蛋白多神经病（ATTR-PN）患者的神经系统进展。对ATTR-PN患者中他法米地的干预，观察和监视研究的安全性数据进行了全面，综合的分析。

方法：汇总了截至2017年1月3日，所有已资助，已完成或正在进行中的ATTR-PN患者中他法米第2/3期研究的安全性数据。还评估了截至2017年1月3日正在进行的运甲状腺素蛋白淀粉样变性结果调查（THAOS）的安全性数据以及截至2017年3月31日的上市后监测报告。

结果：在2/3期研究中，有137例患者（他法米坦暴露的平均持续时间为44.2个月），其中134例（97.8％）经历了≥1种治疗紧急不良事件（TEAE），46例（33.6％）经历了≥1种治疗-紧急严重不良事件（TESAE）。最常见的TEAE是腹泻（26.3％），尿路感染（UTI; 25.5％）和流行性感冒（21.2％）。在THAOS中，有661名受试者接受了他法米地暴露（平均持续时间27.6个月），其中250名（37.8％）经历了≥1 TEAE，而96名（14.5％）经历了1 TESAE。最常见的TEAE是UTI（6.1％）。上市后的监督报告通常反映了他法米地的已知安全性。

结论：该分析未发现任何重要的新安全性发现；他法达昔在ATTR-PN患者中通常是安全的且耐受性良好。

试用注册： ClinicalTrials.gov标识符：NCT00409175。

试用注册： ClinicalTrials.gov标识符：NCT00791492。

试用注册： ClinicalTrials.gov标识符：NCT00630864。

试用注册： ClinicalTrials.gov标识符：NCT01435655。

试用注册： ClinicalTrials.gov标识符：NCT00925002。

试用注册： ClinicalTrials.gov标识符：NCT00628745。