Ruxolitinib for the treatment of myelofibrosis: its clinical potential.
Ruxolitinib for the treatment of myelofibrosis: its clinical potential.
复制标题
违反骨纤维化治疗骨髓纤维化：其临床潜力。
DOI：
10.2147/tcrm.s23277
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发表时间：
2012
影响因子：
2.8
通讯作者：
Verstovsek S
中科院分区：
文献类型：
--
作者：
Ostojic A;Vrhovac R;Verstovsek S
Ruxolitinib 是一种口服生物可利用的选择性 Janus 激酶 (JAK) 1 和 2 抑制剂，被批准用于治疗骨髓纤维化 (MF)，这是一种骨髓疾病，其中 JAK 通路失调，导致造血和免疫功能受损。通过抑制 JAK1 和 JAK2，鲁索替尼调节细胞因子刺激的细胞内信号传导。在一项针对 MF 患者的 II 期临床试验中，鲁索替尼接受者在有或没有 JAK2 突变的患者中表现出脾脏大小持久减小、循环促炎细胞因子减少、体力活动改善、体重增加以及症状（包括全身症状）减轻。这些发现得到了两项 III 期临床 MF 研究的证实，其中一项研究中，与安慰剂相比，鲁索替尼接受者在第 24 周时脾脏体积较基线减少 ≥35%（41.9% 对比 0.7%；P < 0.0001），另一项研究中采用最佳可用治疗（31.9% 对比 0%；P < 0.0001）。鲁索替尼接受者的 MF 症状缓解和生活质量改善也显着更大。接受鲁索替尼治疗的患者的总生存期显着长于接受安慰剂的患者。由于存在潜在严重不良反应（例如骨髓抑制）的风险，鲁索替尼应在医生的密切监督下使用。需要对 III 期 MF 研究进行更长时间的随访，才能就鲁索替尼改变自然病程的能力得出明确的结论。
Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK) 1 and 2 inhibitor approved for the treatment of myelofibrosis (MF), a bone marrow disease in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine-stimulated intracellular signaling. In a phase II clinical trial in patients with MF, ruxolitinib recipients exhibited durable reductions in spleen size, reductions in circulating pro-inflammatory cytokines, improvements in physical activity, weight gain, and alleviation of symptoms (including constitutional symptoms) in patients with and without JAK2 mutation. These findings were confirmed by two phase III clinical MF studies, in which a greater proportion of ruxolitinib recipients achieved a spleen volume reduction of ≥35% from baseline at week 24, compared with placebo in one study (41.9% versus 0.7%; P < 0.0001) and with best available therapy in the other (31.9% versus 0%; P < 0.0001). Alleviation of MF symptoms and improvements in quality of life were also significantly greater in ruxolitinib recipients. Overall survival of patients treated with ruxolitinib was significantly longer than of those receiving the placebo. Owing to risks of potentially serious adverse effects, eg, myelosuppression, ruxolitinib should be used under close physician supervision. Longer follow-up of the phase III MF studies is needed to reach firm conclusions regarding ruxolitinib’s capacity to modify the natural disease course.