Sean M. Healey & AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts.
Muscle Nerve. 2021 Jan;63(1):31-39. doi: 10.1002/mus.27091. Epub 2020 Oct 30.
An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.
口服固定剂量苯丁酸钠-牛磺酸二醇(PB-TURSO)复方制剂在 ALS 的随机、安慰剂对照、2 期临床试验(CENTAUR)中显著减缓了功能下降。在此,我们报告了 CENTAUR 参与者的长期生存分析结果。在 CENTAUR 中,ALS 成人患者以 2:1 的比例随机分配至 PB-TURSO 或安慰剂。完成 6 个月(24 周)随机阶段的参与者有资格在开放标签扩展中接受 PB-TURSO。全因死亡率分析(随机分组后最长 35 个月随访)纳入了所有随机参与者。在本分析的随访期间,参与者和现场研究人员对治疗分配保持盲态。在最初随机分配到 CENTAUR 的 137 名参与者中,有 135 名获得了生存状态。最初随机分配至 PB-TURSO 的参与者的中位总生存期为 25.0 个月,最初随机分配至安慰剂的参与者为 18.5 个月(风险比,0.56;95%置信区间,0.34-0.92;P =.023)。与安慰剂相比,基线时开始使用 PB-TURSO 治疗可使中位生存期延长 6.5 个月。与 CENTAUR 的结果相结合,这些结果表明 PB-TURSO 在 ALS 中具有功能和生存获益。