Oritani Kenji, Ohishi Kohshi, Okamoto Shinichiro, Kirito Keita, Komatsu Norio, Tauchi Tetsuzo, Handa Hiroshi, Saito Shigeki, Takenaka Katsuto, Shimoda Kazuya, Okada Hikaru, Amagasaki Taro, Wakase Shiho, Shimozuma Kojiro, Akashi Koichi
a Department of Hematology, Graduate School of Medical Sciences , International University of Health and Welfare Hospital , Tochigi , Japan.
b Blood Transfusion Service, Mie University Hospital , Mie , Japan.
Curr Med Res Opin. 2018 Mar;34(3):531-537. doi: 10.1080/03007995.2017.1415874. Epub 2018 Jan 4.
Myelofibrosis (MF) is associated with a significant symptom burden that severely impacts patient quality-of-life (QoL). Ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, led to substantial improvements in splenomegaly, MF-associated symptoms, and QoL in the phase 3 COMFORT studies, proving superior to placebo and best available therapy. This study evaluated the effect of ruxolitinib on symptoms and QoL in Japanese patients with MF.
A pooled analysis of studies A2202 (NCT01392443) and AJP01 (NCT02087059) of ruxolitinib in Japanese patients with MF (n = 81) was conducted. Changes in total symptom score (TSS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were summarized.
Most patients received a starting dose of 15 or 20 mg twice daily (BID) and had a final titrated dose of ≥10 mg BID. Overall, 67.7% (44/65) achieved a ≥50% reduction from baseline in TSS at week 24. Reductions in TSS were seen in every dose group; the greatest reductions occurred in patients with a final titrated dose of 20 or 25 mg BID. Improvements in QoL were seen in patients who achieved a ≥50% reduction in TSS. Generally, improvements in TSS and individual symptoms correlated with reductions in spleen size, with those having a ≥35% reduction in spleen volume having the greatest improvements.
Consistent with COMFORT-I, ruxolitinib provided substantial improvements in symptoms and QoL in Japanese patients with MF, with higher doses of ruxolitinib associated with better responses.
骨髓纤维化（MF）伴有严重的症状负担，严重影响患者的生活质量（QoL）。芦可替尼是一种有效的Janus激酶1（JAK1）/JAK2抑制剂，在3期COMFORT研究中可显著改善脾肿大、MF相关症状和QoL，证明优于安慰剂和最佳可用疗法。本研究评估了芦可替尼对日本MF患者症状和QoL的影响。
对芦可替尼治疗日本MF患者（n = 81）的研究A2202（NCT01392443）和AJP01（NCT02087059）进行汇总分析。总结了总症状评分（TSS）和欧洲癌症研究与治疗组织生活质量问卷核心30的变化。
大多数患者起始剂量为每日两次（BID）15或20 mg，最终滴定剂量≥10 mg BID。总体而言，67.7%（44/65）的患者在第24周时TSS较基线降低≥50%。每个剂量组的TSS均有降低；最终滴定剂量为20或25 mg BID的患者降低幅度最大。TSS降低≥50%的患者QoL有所改善。一般来说，TSS和个体症状的改善与脾脏大小的减小相关，脾脏体积减小≥35%的患者改善最大。
与COMFORT-I一致，芦可替尼使日本MF患者的症状和QoL有显著改善，较高剂量的芦可替尼反应更好。
