Osteonecrosis of the Jaw Caused by Denosumab in Treatment-Naïve and Pre-Treatment with Zoledronic Acid Groups: A Time-to-Onset Study Using the Japanese Adverse Drug Event Report (JADER) Database

• Published in: Drugs - Real World Outcomes 2022-12, Vol.9 (4), p.659-665
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Acids; Brand names; Cancer; Drug dosages; Fractures; Internal Medicine; Ligands; Medical personnel; Medicine; Medicine & Public Health; Metastasis; Monoclonal antibodies; Multiple myeloma; Necrosis; Original; Original Research Article; Osteoporosis; Pharmacology/Toxicology; Pharmacotherapy; Quality of life; Statistical analysis
• ISSN: 2199-1154; 2198-9788
• DOI: 10.1007/s40801-022-00324-4

Background 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). Objective 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. Methods 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. Results 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). Conclusions 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.