Hasegawa Shiori, Ikesue Hiroaki, Satake Riko, Inoue Misaki, Yoshida Yu, Tanaka Mizuki, Matsumoto Kiyoka, Wakabayashi Wataru, Oura Keita, Muroi Nobuyuki, Hashida Tohru, Iguchi Kazuhiro, Nakamura Mitsuhiro
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, 501-1198, Japan.
Kaneichi Pharmaceutical. Co., Ltd, 3-5-23, Himejima, Nishiyodogawa-ku, Osaka, 555-0033, Japan.
Drugs Real World Outcomes. 2022 Dec;9(4):659-665. doi: 10.1007/s40801-022-00324-4. Epub 2022 Aug 6.
Medication-related osteonecrosis of the jaw is a serious adverse event associated with bone-modifying agents, such as injectable bisphosphonate (zoledronic acid) and the anti-receptor activator of nuclear factor-κB ligand antibody (denosumab).
This study aims to evaluate and compare the time-to-onset profile for medication-related osteonecrosis of the jaw associated with denosumab between treatment-naïve (naïve group) and pre-treatment with zoledronic acid (post-zoledronic acid group) patients using the Japanese Adverse Drug Event Report database.
Medication-related osteonecrosis of the jaw was defined according to the Medical Dictionary for Regulatory Activities. The medication-related osteonecrosis of the jaw onset profiles were evaluated using the Weibull shape parameter and the log-rank test.
The Japanese Adverse Drug Event Report database contains 632,409 reports published between April 2004 and March 2020. In the time-to-onset analysis, after extracting the combinations with complete information for the treatment start date and the medication-related osteonecrosis of the jaw onset date, 272 reports of the naïve group and 86 reports of the post-zoledronic acid group were analyzed. The median onset in the naïve and post-zoledronic acid groups was 487.0 (25-75%: 274.0-690.8) and 305.5 (25-75%: 158.3-508.5) days, respectively. Medication-related osteonecrosis of the jaw occurred earlier in the post-zoledronic acid group than in the naïve group, and the log-rank test demonstrated a significant difference in their time transitions (p < 0.0001).
The results indicated a risk of medication-related osteonecrosis of the jaw in naïve and post-zoledronic acid groups and a shorter onset time in the latter than in the former. Thus, healthcare professionals should take the early risk of medication-related osteonecrosis of the jaw into account when switching patients from zoledronic acid to denosumab treatment.
药物相关性颌骨坏死是一种与骨改良剂相关的严重不良事件，如注射用双膦酸盐（唑来膦酸）和抗核因子κB受体活化剂配体抗体（地诺单抗）。
本研究旨在利用日本药品不良事件报告数据库，评估和比较初治患者（初治组）和曾接受唑来膦酸治疗的患者（唑来膦酸治疗后组）中与地诺单抗相关的药物相关性颌骨坏死的发病时间情况。
根据《监管活动医学词典》定义药物相关性颌骨坏死。使用威布尔形状参数和对数秩检验评估药物相关性颌骨坏死的发病情况。
日本药品不良事件报告数据库包含2004年4月至2020年3月期间发布的632,409份报告。在发病时间分析中，提取治疗开始日期和药物相关性颌骨坏死发病日期信息完整的组合后，分析了初治组的272份报告和唑来膦酸治疗后组的86份报告。初治组和唑来膦酸治疗后组的中位发病时间分别为487.0天（25%-75%：274.0-690.8天）和305.5天（25%-75%：158.3-508.5天）。唑来膦酸治疗后组的药物相关性颌骨坏死比初治组更早发生，对数秩检验显示两组的时间变化有显著差异（p<0.0001）。
结果表明初治组和唑来膦酸治疗后组均有发生药物相关性颌骨坏死的风险，且后者的发病时间比前者短。因此，医疗保健专业人员在将患者从唑来膦酸治疗转换为地诺单抗治疗时，应考虑到药物相关性颌骨坏死的早期风险。
