Characteristics associated with clinical response to pomalidomide in hereditary hemorrhagic telangiectasia.

Pomalidomide was recently demonstrated to be efficacious for bleeding in HHT in the landmark PATH-HHT trial. Given that the vascular remodeling that results in bleeding improvement may require several months, characteristics associated with treatment response would be invaluable to plan treatment.

最近在标志性的PATH-HHT试验中证明了波马利多米德对于HHT出血的有效性。鉴于导致出血改善的血管重塑可能需要数月时间，与治疗反应相关的特征对于规划治疗将非常宝贵。

Using data from PATH-HHT (NCT03910244), we identified characteristics associated with change from baseline in Epistaxis Severity Score (ESS; a well-validated 10-point HHT bleeding scale and the trial's primary end point) using multivariable-adjusted repeated-measures models.

利用PATH-HHT (NCT03910244)的数据，我们使用多变量调整的重复测量模型确定了与基线期鼻出血严重程度评分（ESS；一个经过验证的10分HHT出血量表，也是试验的主要终点）变化相关的特征。

Characteristics associated with a better response to pomalidomide at weeks 16 to 24 of the trial included a higher (more severe) baseline ESS (change from baseline, -0.76 [95% confidence interval(CI), -0.99 to -0.54] points per 1-point higher baseline score, P< .001) and concomitant antifibrinolytic therapy (-0.73 [95% CI, -1.48 to 0.01] vs no therapy, P = .05).

试验第16至24周对波马利多米德反应较好的特征包括较高的（更严重的）基线ESS（基线期每增加1分，变化为-0.76 [95%置信区间（CI），-0.99至-0.54]分，P< .001）和联合抗纤溶治疗（与无治疗相比，-0.73 [95% CI, -1.48至0.01]，P = .05）。

Characteristics associated with a less robust response were older age (0.29 [95% CI, 0.05-0.53] per 10 years older, P = .02) and underlying ACVRL1 germ line mutation (0.62 [95% CI, -0.04 to 1.27] vs ENG, SMAD4, or mutation not known, P = .06].

与较弱反应相关的特征是年龄较大（每增加10岁，效应量为0.29 [95% 置信区间, 0.05-0.53]，P = .02）和潜在的ACVRL1基因突变（效应量为0.62 [95% 置信区间, -0.04至1.27]，与ENG、SMAD4或未知突变相比，P = .06）。

Characteristics notably associated with placebo response (placebo effect) were patient-reported outcome measures, such that those experiencing more severe disease at baseline had less placebo effect.

与安慰剂反应（安慰剂效应）显著相关的特征是患者报告的结果指标，即那些在基线时疾病较严重的患者，其安慰剂效应较小。

In conclusion, several baseline patient and disease characteristics were associated with pomalidomide response, findings that may help guide patient selection for the use of pomalidomide in HHT.

总之，几项基线患者和疾病特征与泊马度米德反应相关，这些发现可能有助于指导在HHT中使用泊马度米德的患者选择。

This trial was registered at www.Clinicaltrials.gov as NCT03910244.

该试验已在www.Clinicaltrials.gov注册，注册号为NCT03910244。