Department of Neurology, Hospital of the University of Pennsylvania, University of Pennsylvania, 3400 Spruce St, 3 Gates, Philadelphia, PA, 19104, USA.
Department of Cardiology, University of Pennsylvania, Philadelphia, PA, USA.
Orphanet J Rare Dis. 2024 May 8;19(1):191. doi: 10.1186/s13023-024-03198-7.
There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy.
To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy.
We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality.
One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21).
While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy.
目前已有新型药物获批用于治疗遗传性转甲状腺素蛋白淀粉样变性（ATTRv），这些药物分为转甲状腺素蛋白（TTR）稳定剂和基因沉默剂。虽然许多患者可能同时使用这两类药物，但尚无关于联合治疗安全性和疗效的相关数据。
描述美国队列中ATTRv 患者和 TTR 靶向治疗的特征，并比较联合治疗与单药治疗的结果。
我们对一家医疗机构在 2018 年 1 月至 2022 年 12 月期间诊治的 ATTRv 患者的电子病历数据进行了回顾性队列研究。我们收集了患者的症状、基因突变、疾病严重程度、ATTRv 治疗、住院和死亡率等数据。
共纳入 162 例 ATTRv 患者，诊断时的平均年龄为 65 岁。86 例（53%）患者携带 V122I 变异。119 例患者有症状，其中 103 例接受了 ATTRv 特异性治疗。41 例（40%）患者仅患有心肌病，53 例（51%）患者为心肌病和周围神经病混合表型。38 例（37%）患者接受了基因沉默剂和蛋白稳定剂联合治疗。在开始治疗后，有 9 例（15%）单药治疗组患者发生了两次或更多次心脏住院，而 3 例（9%）联合治疗组患者发生了心脏住院（p=0.26）。与单药治疗相比，联合治疗组患者的全因死亡率调整后风险比为 0.37（0.08-1.8，p=0.21）。
尽管联合治疗的疗效尚未得到证实，但超过三分之一的 ATTRv 患者同时使用稳定剂和沉默剂。联合治疗未出现安全性问题。联合治疗组患者的住院和生存情况有改善趋势，但无统计学意义。需要进行更大规模、随访时间更长的研究来确定联合治疗的获益。
