Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, 399-8101, Japan.
Healthcare R&D Center, Asahi Kasei Corporation, 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, 100-0006, Japan.
Calcif Tissue Int. 2021 Dec;109(6):666-674. doi: 10.1007/s00223-021-00884-7. Epub 2021 Jul 10.
In a clinical trial involving Japanese patients with osteoporosis, post hoc analyses were performed to evaluate the incidence of acute phase reactions (APRs) after infusion of zoledronic acid (ZOL). The results highlighted differences in baseline factors between patients with vs without APRs. Changes in efficacy indicators such as bone turnover markers (BTMs) also showed significant differences. We, therefore, investigated the factors involved in the development of APRs in Japanese patients treated with a once-yearly intravenous infusion of ZOL 5 mg for 2 years by assessing the relation between APRs and efficacy. APRs reported in patients with primary osteoporosis from the ZONE study were analyzed post hoc. Baseline factors were compared in patients with vs without APRs, and changes in BTMs and bone mineral density (BMD) were also investigated. In the ZOL group, 51.2% (169/330) of patients developed APRs after the first infusion and 12.3% (33/268) after the second infusion. Comparison of baseline factors showed that patients without APRs in the ZOL group had a significantly higher neutrophil/lymphocyte ratio, lower serum levels of procollagen type I N-terminal propeptide, older age, and higher likelihood of prior bisphosphonate use vs patients with APRs. Patients with APRs showed significantly higher increases in total hip BMD at 6 and 12 months and larger reductions in BTMs vs patients without APRs. Patient profiles differed significantly between patients with vs without APRs, with APRs after the first infusion of ZOL being related to increases in total hip BMD and suppression of BTMs.This study is registered with ClinicalTrials.gov (identifier: NCT01522521; January 31, 2012).
在一项涉及日本骨质疏松症患者的临床试验中，进行了事后分析，以评估唑来膦酸（ZOL）输注后急性相反应（APR）的发生率。结果突出了有 APR 与无 APR 患者之间基线因素的差异。骨转换标志物（BTM）等疗效指标的变化也显示出显著差异。因此，我们通过评估 APR 与疗效之间的关系，研究了日本患者接受每年一次静脉输注 ZOL 5mg 治疗 2 年时 APR 发展的相关因素。对 ZONE 研究中原发性骨质疏松症患者的 APR 进行了事后分析。比较了有 APR 与无 APR 患者的基线因素，并研究了 BTM 和骨密度（BMD）的变化。在 ZOL 组中，第一次输注后 51.2%（169/330）的患者出现 APR，第二次输注后 12.3%（33/268）的患者出现 APR。基线因素比较显示，ZOL 组中无 APR 的患者中性粒细胞/淋巴细胞比值较高，I 型前胶原氨基端前肽水平较低，年龄较大，且既往使用双膦酸盐的可能性较高。与无 APR 的患者相比，有 APR 的患者在 6 个月和 12 个月时总髋部 BMD 增加显著更大，BTM 降低显著更大。有 APR 与无 APR 的患者之间的患者特征存在显著差异，ZOL 首次输注后的 APR 与总髋部 BMD 的增加和 BTM 的抑制有关。本研究在 ClinicalTrials.gov 注册（标识符：NCT01522521；2012 年 1 月 31 日）。
