Ianalumab plus Eltrombopag in Immune Thrombocytopenia.

Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP.

Ianalumab是一种针对B细胞的单克隆抗体，目前正在作为ITP的短期二线治疗方案进行评估。

Methods

In this phase 3, randomized, double-blindtrial, we assigned, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive ianalumab at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months.

在这项III期、随机、双盲试验中，我们以1:1:1的比例，为对一线糖皮质激素治疗反应不足或复发的原发性ITP成人患者分配了每月一次，为期4个月的9毫克或3毫克/公斤体重的ianalumab治疗或安慰剂。

Eltrombopag, an oral thrombopoietin-receptor agonist, was administered once daily in each group according to local prescribing information; the dose was tapered until discontinuation by the end of week 24 in eligible patients.

Eltrombopag，一种口服血小板生成素受体激动剂，根据当地处方信息，每天一次给予每个组的患者；在第24周末，符合条件的患者逐渐减量直至停药。

The primary end point was freedom from treatment failure, as determined in a time-to-event analysis, with treatment failure defined by a platelet count of less than 30×109 per liter more than 8 weeks after randomization, initiation of rescue therapy more than 8 weeks after randomization, initiation of new ITP therapy, inability to taper or discontinue eltrombopag because of an inadequate platelet count, or death from any cause, whichever occurred first.

主要终点是治疗失败的无病生存，通过时间至事件分析确定，治疗失败定义为随机化后超过8周血小板计数低于30×10^9/L，随机化后超过8周开始使用救援治疗，开始新的ITP治疗，因血小板计数不足而无法减少或停用eltrombopag，或任何原因导致的死亡，以先发生者为准。

The key secondary end point was a stable response at 6 months, defined by a platelet count of at least 50×109 per liter in at least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy.

关键次要终点是6个月时的稳定反应，定义为在第19周至第25周之间至少75%的测量中血小板计数至少为50×10^9/L，且在此期间未使用救援治疗或新的ITP治疗。

Safety was assessed.

安全性得到了评估。

Results

A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group.

共有152名患者进行了随机分组：50名患者分入9毫克的ianaumab组，51名患者分入3毫克的ianaumab组，另外51名患者分入安慰剂组。

The estimated probability of being free from treatment failure at 12 months was 54% (95% confidence interval[CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group.

在9毫克组中，12个月无治疗失败的估计概率为54%（95%置信区间[CI]，39至67），在3毫克组中为51%（95% CI，36至64），在安慰剂组中为30%（95% CI，18至43）。

The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratiofor treatment failure (ianalumab vs. placebo) was 0.55 (P = 0.04) in the 9-mg group and 0.58 (P = 0.045) in the 3-mg group.

与安慰剂加艾曲波帕相比，伊纳拉单抗加艾曲波帕的治疗失败时间显著延长；在9毫克组中，治疗失败的估计风险比（伊纳拉单抗对安慰剂）为0.55（P = 0.04），在3毫克组中为0.58（P = 0.045）。

The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P = 0.045).

在6个月时，9毫克组患者病情稳定的百分比显著高于安慰剂组（62%对39%；P = 0.045）。

The overall frequency of adverse events during the treatment period was generally similar in the three groups.

治疗期间，三组中不良事件的总体发生频率大致相似。

The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group.

9-mg组严重不良事件的发生频率为16%，3-mg组为6%，安慰剂组为4%。

Conclusions

Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag.

Ianalumab联合eltrombopag比安慰剂联合eltrombopag导致治疗失败的时间更长。

(Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.).

(由诺华公司资助; VAYHIT2 ClinicalTrials.gov编号, NCT05653219。)