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).
Keywords: Efficacy; Hereditary transthyretin amyloidosis; Japan; Postmarketing surveillance; Safety; Tafamidis meglumine.
© 2025 The Author(s).
