Sirturo获准用于治疗多耐药结核

圣路易斯(MD Consult)——2012年12月28日，美国食品药品管理局(FDA)宣布，已加速批准Sirturo(bedaquiline)作为其他治疗无效的成人多耐药肺结核的联合治疗组成部分。Sirturo是首个获准用于治疗多耐药结核的药物，而且应与其他抗结核药物联用。该药通过抑制结核分枝杆菌复制和扩散所必需的酶而发挥疗效。

Sirturo的安全性和有效性已在纳入440例患者的两项2期临床试验中得到了证实。在第一项试验中，受试者被随机分为Sirturo+其他抗结核药物组和安慰剂+其他抗结核药物组。第二项试验目前仍在进行中，所有受试者均接受Sirturo+其他抗结核药物治疗。这两项研究均以评价至痰培养阴转(SCC)时间为预定目标。第一项试验结果显示，接受Sirturo联合治疗的患者至SCC中位时间为83天，而接受安慰剂联合治疗的患者为125天。第二项试验显示，至SCC中位时间为57天，进一步支持了前一项试验的结果。

临床试验中的常见不良反应包括恶心、关节痛和头痛。

Sirturo的标签中含有一则加框警告，标明该药可能影响心脏电活动(QT间期延长)，可导致潜在致死性心律失常。在接受Sirturo治疗的患者中有9例死亡，而接受安慰剂治疗者仅死亡2例。5例Sirturo组死亡患者和2例安慰剂组死亡患者似乎死于结核，而其余4例Sirturo组死亡患者的死亡原因不明确。

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ST LOUIS (MD Consult) - On December 28, 2012, the US Food and Drug Administration (FDA) announced the accelerated approval of Sirturo (bedaquiline) as part of combination therapy to treat adults with multidrug resistant pulmonary tuberculosis (TB) when other alternatives are not available. Sirturo is the first drug approved to treat multidrug resistant TB and should be used in combination with other drugs used to treat TB. The drug works by inhibiting an enzyme needed by Mycobacterium tuberculosis to replicate and spread throughout the body.

Sirturo's safety and effectiveness were established in 440 patients in 2 phase 2 clinical trials. Patients in the first trial were randomly assigned to treatment with Sirturo plus other drugs used to treat TB, or placebo plus other drugs used to treat TB. All patients in the second trial, which is ongoing, received Sirturo plus other TB drugs. Both studies were designed to measure the length of time to sputum culture conversion (SCC). Results from the first trial showed patients treated with Sirturo combination therapy achieved SCC in a median time of 83 days, compared with 125 days in patients treated with placebo combination therapy. Results from the second trial showed the median time to SCC was 57 days, supporting the efficacy findings of the first trial.

Common adverse effects identified in the clinical trials include nausea, joint pain, and headache.

The Sirturo label carries a Boxed Warning concerning the affect the drug may have cardiac electrical activity (QT prolongation), which could lead to an abnormal and potentially fatal heart rhythm. Nine patients who received Sirturo died compared with 2 patients who received placebo. Five of the deaths in the Sirturo group and all of the deaths in the placebo arm seemed to be related to TB, but no consistent reason for the deaths in the remaining Sirturo-treated patients could be identified.