Impact of concomitant azoles on ruxolitinib treatment in patients with GVHD: post hoc analyses of REACH2 and REACH3.

Post hoc analyses of the REACH2/REACH3 phase 3 trials examined the impact of these clinically relevant drug interactions on ruxolitinib treatment outcomes in patients with steroid-refractory acute GVHD (aGVHD; REACH2) and steroid-refractory/steroid-dependent chronic GVHD (cGVHD; REACH3).

REACH2/REACH3第三阶段试验的事后分析检查了这些临床相关的药物相互作用对鲁索替尼治疗结果的影响，研究对象为对类固醇耐药的急性移植物抗宿主病（aGVHD; REACH2）患者以及对类固醇耐药/依赖的慢性移植物抗宿主病（cGVHD; REACH3）患者。

In REACH2, overall response rate (ORR) at day 28 was significantly higher with ruxolitinib vs best available therapy (BAT; 67.5% vs 44.3%; P = .0003) among patients who received concomitant azoles; among those who did not, day 28 ORR was 45.9% vs 28.6%, respectively.

在REACH2研究中，第28天时，接受联合抗真菌药物治疗的患者中，使用鲁索替尼治疗的总缓解率（ORR）显著高于最佳可用治疗（BAT；67.5%对比44.3%；P = .0003）；而在未接受联合抗真菌药物治疗的患者中，第28天的ORR分别为45.9%和28.6%。

In REACH3, ORR at week 24 was significantly higher with ruxolitinib vs BAT in patients who did (46.6% vs 29.4%; P = .006) or did not receive (57.1% vs 19.4%; P < .0001) concomitant azoles.

在REACH3研究中，第24周时，无论是否接受联合抗真菌药物治疗，使用鲁索替尼治疗的患者总缓解率（ORR）均显著高于最佳可用治疗（BAT），接受联合治疗的患者ORR为46.6%对比29.4%（P = .006），未接受联合治疗的患者ORR为57.1%对比19.4%（P < .0001）。

Concomitant azoles neither increased the rate of cytopenias in patients treated with ruxolitinib in REACH2/REACH3, nor affected the median dose of ruxolitinib up to day 28 in REACH2 (azoles/no azoles, 20.0 mg/d [range, 9.0-21.0]/20.0 mg/d [range, 8.4-20.0]) or week 24 in REACH3 (azoles/no azoles, 19.4 mg/d [range, 4.8-20.5]/19.9 mg/d [range, 5.5-20.0]).

在REACH2/REACH3研究中，同时使用唑类药物并未增加接受鲁索替尼治疗患者的细胞减少症发生率，也未影响到第28天为止的鲁索替尼中位剂量（REACH2研究中，唑类药物/无唑类药物，20.0 mg/d [范围，9.0-21.0]/20.0 mg/d [范围，8.4-20.0]；REACH3研究中，第24周，唑类药物/无唑类药物，19.4 mg/d [范围，4.8-20.5]/19.9 mg/d [范围，5.5-20.0]）。

Patients receiving concomitant azoles were more likely to have ruxolitinib dose modifications in REACH2/REACH3, highlighting the importance of dose optimization in these patients.

在REACH2/REACH3研究中，接受同时使用唑类药物的患者更有可能需要调整鲁索替尼剂量，这强调了在这些患者中进行剂量优化的重要性。

Overall, concomitant azole treatment was generally well tolerated and did not affect treatment outcomes with appropriate ruxolitinib dose optimization.

总体而言，合并使用唑类药物治疗通常耐受性良好，并且在适当调整鲁索利替尼剂量的情况下，并不影响治疗结果。

Consistent with primary REACH2/REACH3 results, ruxolitinib provided greater clinical benefit than BAT in patients with steroid-refractory aGVHD and steroid-refractory/steroid-dependent cGVHD, irrespective of concomitant azole treatment.

与主要的REACH2/REACH3研究结果一致，鲁索利替尼在治疗对类固醇耐药的急性移植物抗宿主病（aGVHD）和对类固醇耐药/依赖的慢性移植物抗宿主病（cGVHD）患者方面，比BAT提供了更大的临床益处，无论是否合并使用唑类药物。

These trials were registered at www.ClinicalTrials.gov as #NCT02913261 (REACH2) and #NCT03112603 (REACH3).

这些试验已在www.ClinicalTrials.gov注册，编号为#NCT02913261（REACH2）和#NCT03112603（REACH3）。