Evaluation of medication-related osteonecrosis of the jaw using the Japanese Adverse Drug Event Report database

Abstract

BackgroundBisphosphonates (BPs) and denosumab are widely used to treat osteoporosis and complications associated with bone metastases. However, medication-related osteonecrosis of the jaw (MRONJ) is a serious problem.ObjectiveThe objective of this study was to evaluate the frequency, outcome, and characteristics of patients with drug-induced MRONJ.MethodsRetrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database from the Pharmaceuticals and Medical Devices Agency. Adverse event reports submitted to JADER between 2004 and 2017 were analyzed, and the reporting odds ratio (ROR) was calculated.ResultsAmong the BPs that cause MRONJ, zoledronate was the most common; therefore, we compared the characteristics of cases of MRONJ induced by zoledronate with those induced by denosumab. Among the 3,875 (68.1% women) cases of MRONJ, zoledronate-related MRONJ accounted for 1,283 (56.0% women) and denosumab-related MRONJ accounted for 322 (55.3% women). MRONJ was more frequent after 70 years of age regardless of the use of either zoledronate or denosumab; onset occurred after 1 year from the denosumab treatment, but it is unknown when onset occurred after zoledronate treatment. The outcomes for MRONJ were poor, with 406 reports on zoledronate (31.6%) and 152 reports on denosumab (47.2%) demonstrating nonrecovery. Zoledronate (ROR: 319.3, 95% CI: 296.0–344.4) had the highest ROR among BP agents. Denosumab had a high ROR (ROR: 155.2, 95% CI: 136.5–176.3). Zoledronate and denosumab were used in similar patient backgrounds, and their use resulted in a similar frequency of MRONJ.ConclusionThe findings of this comprehensive evaluation of MRONJ using the JADER database will be helpful for prescribing medications to elderly patients.

Association of Stevens‐Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs in pediatric patients: Subgroup analysis based on a Japanese spontaneous database

“…The present study used data from the public release of PMDA’s JADER database as a large spontaneous reporting database, from which adverse event reports voluntarily submitted to the PMDA between April 2004 and January 2017 are freely available. The data structure of the JADER consists of four datasets: patient demographic information (DEMO), drug information (DRUG), adverse events (REAC) and medical history (HISTO).…”

“…We compiled a cross‐tabulation table based on two classifications: the presence or absence of the adverse event, and the presence or absence of the suspected medicine. Then, we calculated the ROR as reported previously . The ROR is the rate of reporting a specific adverse event caused by a particular drug divided by the rate of the same adverse event caused by all other drugs present in the database.…”

“…Therefore, unexpected and serious adverse events are sometimes encountered in post‐marketing reports, so pharmacovigilance activities are important to reveal them. In April 2004, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) established a spontaneous reporting system, the Japanese Adverse Drug Event Report (JADER) database, a unitized large‐scale database for pharmacovigilance . The objective of this study was to analyse the characteristics of SJS and TEN associated with AEDs in pediatric patients using a spontaneously reported adverse drug events database in Japan.…”

“…The present study used data from the public release of PMDA's JADER database as a large spontaneous reporting database, 11,[13][14][15] from which adverse event reports voluntarily submitted to the PMDA between April 2004 and January 2017 are freely available.…”

“…Then, we calculated the ROR as reported previously. 11,[13][14][15] The ROR is the rate of reporting a database. In addition, the ROR was frequently used in spontaneous reporting databases as an index of the relative risk of drug-associated adverse events.…”