A biomarker signature to predict complete response to itacitinib and corticosteroids in acute graft-versus-host disease.
A biomarker signature to predict complete response to itacitinib and corticosteroids in acute graft-versus-host disease.
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DOI：
10.1111/bjh.18300
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发表时间：
2022-08
影响因子：
6.5
通讯作者：
Howell, Michael D.
中科院分区：
文献类型：
--
作者：
Pratta, Michael;Paczesny, Sophie;Socie, Gerard;Barkey, Natalie;Liu, Hao;Owens, Sherry;Arbushites, Michael C.;Schroeder, Mark A.;Howell, Michael D.
在急性移植物抗宿主病(GVHD)中，我们进行了广泛的蛋白质组学分析，以确定和评估可能预测口服选择性Janus Kins1(JAK1)抑制剂itacitinib治疗反应的候选生物标记物。来自25名参与者的血浆样本(识别队列；NCT02614612)被用来识别新的生物标记物，这些新生物标记物在安慰剂对照随机试验的验证队列中进行了测试(n=1110；NCT03139604)。确定的队列每天接受一次皮质类固醇加200或300 mg的伊塔西替尼。验证队列接受皮质类固醇加200 mg伊卡西替尼每日一次或安慰剂治疗。使用邻近延伸分析进行了广泛的蛋白质组学分析。基线和纵向比较采用非配对t检验和用于评估生物标记物水平变化的单因素方差分析。确定了7个候选生物标志物。单核细胞趋化蛋白(MCP)3，降钙素/降钙素原(ProCALCA/Calca)，以及先前已确定的预后急性GVHD生物标志物，再生胰岛衍生蛋白(REG)3A，分层完全应答者，从无应答者(进展性疾病参与者)到伊塔西替尼，但不是安慰剂，可能代表伊塔西替尼在急性GVHD中的预测生物标志物。伊卡西替尼在应答者中，随着时间的推移，肿瘤形成抑制因子(ST)2和肿瘤坏死因子受体(TNFR)1的ProCALCA/CALCA显著降低，这可能是治疗反应的生物标志物。新的生物标记物有可能识别对伊他西替尼加皮质类固醇治疗有反应的急性移植物抗宿主病患者(NCT02614612；NCT03139604)。
A broad proteomic analysis was conducted to identify and evaluate candidate biomarkers potentially predictive of response to treatment with an oral selective Janus kinase 1 (JAK1) inhibitor, itacitinib, in acute graft‐versus‐host disease (GVHD). Plasma samples from 25 participants (identification cohort; NCT02614612) were used to identify novel biomarkers that were tested in a validation cohort from a placebo‐controlled, randomised trial (n = 210; NCT03139604). The identification cohort received corticosteroids plus 200 or 300 mg itacitinib once daily. The validation cohort received corticosteroids plus 200 mg itacitinib once daily or placebo. A broad proteomic analysis was conducted using a proximity extension assay. Baseline and longitudinal comparisons were performed with unpaired t‐test and one‐way analysis of variance used to evaluate biomarker level changes. Seven candidate biomarkers were identified. Monocyte‐chemotactic protein (MCP)3, pro‐calcitonin/calcitonin (ProCALCA/CALCA), together with a previously identified prognostic acute GVHD biomarker, regenerating islet‐derived protein (REG)3A, stratified complete responders from non‐responders (participants with progressive disease) to itacitinib, but not placebo, potentially representing predictive biomarkers of itacitinib in acute GVHD. ProCALCA/CALCA, suppressor of tumorigenicity (ST)2, and tumour necrosis factor receptor (TNFR)1 were significantly reduced over time by itacitinib in responders, potentially representing response‐to‐treatment biomarkers. Novel biomarkers have the potential to identify patients with acute GVHD that may respond to itacitinib plus corticosteroid treatment (NCT02614612; NCT03139604).
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影响因子：
7.4
作者：
O'Neal WK;Anderson W;Basta PV;Carretta EE;Doerschuk CM;Barr RG;Bleecker ER;Christenson SA;Curtis JL;Han MK;Hansel NN;Kanner RE;Kleerup EC;Martinez FJ;Miller BE;Peters SP;Rennard SI;Scholand MB;Tal-Singer R;Woodruff PG;Couper DJ;Davis SM;SPIROMICS Investigators
通讯作者：
SPIROMICS Investigators
影响因子：
24.7
作者：
Levine, John E.;Braun, Thomas M.;Harris, Andrew C.;Holler, Ernst;Taylor, Austin;Miller, Holly;Magenau, John;Weisdorf, Daniel J.;Ho, Vincent T.;Bolanos-Meade, Javier;Alousi, Amin M.;Ferrara, James L. M.
通讯作者：
Ferrara, James L. M.
影响因子：
4.3
作者：
Levine, John E.;Logan, Brent;Weisdorf, Daniel
通讯作者：
Weisdorf, Daniel
影响因子：
3.3
作者：
Massi, Daniela;Fondi, Cristina;Bosi, Alberto
通讯作者：
Bosi, Alberto
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y