Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Mayo Clin Proc. 2011 Dec;86(12):1188-91. doi: 10.4065/mcp.2011.0518. Epub 2011 Oct 27.
Ruxolitinib (INCB018424) is a JAK1 and JAK2 inhibitor recently evaluated for the treatment of myelofibrosis (MF) in early- and advanced-phase clinical trials. In 2 recent communications that focused on short-term and long-term ruxolitinib treatment outcome, respectively, the drug was shown to be effective in controlling constitutional symptoms and splenomegaly but was also associated with important adverse effects, including moderate to severe thrombocytopenia and anemia. The most recent of the 2 communications focused on 51 Mayo Clinic patients who participated in the original phase 1/2 ruxolitinib clinical trial and highlighted a high treatment discontinuation rate (92% after a median time of 9.2 months), primarily for loss of treatment benefit but also because of drug-associated adverse effects. The report also discussed the occurrence of sometimes severe withdrawal symptoms during ruxolitinib treatment discontinuation. This "ruxolitinib withdrawal syndrome" was characterized by acute relapse of disease symptoms, accelerated splenomegaly, worsening of cytopenias, and occasional hemodynamic decompensation, including a septic shocklike syndrome. In the current sponsor-independent analysis, we describe the details of these events in 5 severely affected cases (11%) among 47 Mayo Clinic patients with MF in whom ruxolitinib therapy had been discontinued. Our experience calls for full disclosure of the ruxolitinib withdrawal syndrome to patients with MF before initiating ruxolitinib therapy, and treatment discontinuation must be done under close physician supervision and preferably in a tapering schedule.
芦可替尼（INCB018424）是一种 JAK1 和 JAK2 抑制剂，最近在骨髓纤维化（MF）的早期和晚期临床试验中进行了评估。在最近的两项分别关注短期和长期芦可替尼治疗结果的通讯中，该药物被证明在控制全身症状和脾肿大方面有效，但也与重要的不良反应相关，包括中重度血小板减少症和贫血。这两项通讯中最近的一项侧重于 51 名参加原始 1/2 期芦可替尼临床试验的梅奥诊所患者，并强调了高治疗停药率（中位数时间为 9.2 个月后为 92%），主要是因为失去治疗益处，也因为药物相关的不良反应。该报告还讨论了在芦可替尼治疗停药期间有时出现严重戒断症状的情况。这种“芦可替尼戒断综合征”的特点是疾病症状急性复发、脾肿大加速、血细胞减少恶化，偶尔出现血流动力学失代偿，包括类似败血症休克的综合征。在目前的独立赞助者分析中，我们描述了在 47 名因 MF 而停止芦可替尼治疗的梅奥诊所患者中 5 名严重影响病例（11%）中这些事件的细节。我们的经验呼吁在开始芦可替尼治疗前向 MF 患者充分披露芦可替尼戒断综合征，并且必须在医生密切监督下进行停药，最好采用逐渐减量的方案。
