Objective: To evaluate the real-world risk of hypocalcemia in Japanese patients with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) newly initiated on denosumab (PRALIA^®) versus those receiving DMARDs alone.

Design: Observational cohort study utilizing data obtained from the Medical Information Database Network (MID-NET^®) in Japan.

Methods: Patients were eligible if they had a prescription record for any DMARD during the study period (July 2016-December 2020), with their RA diagnosis ＜30 days before the date of DMARD prescription. Primary and secondary outcomes included the incidence of hypocalcemia (serum calcium level ＜8.50 mg/dL), and severe hypocalcemia (serum calcium level ＜7.00 mg/dL), respectively. Data was classified according to denosumab-exposure versus non-exposure, with outcomes assessed during the follow-up period.

Results: Overall, 4,222 patients (denosumab-exposed patients: N＝293; non-exposed patients: N＝3,929) met the study criteria. Hypocalcemia occurred in 4.8％（95％CI: 2.6-­7.9) of denosumab-exposed patients and 1.0％（95％CI: 0.7-­1.4) of non-exposed patients, for an adjusted risk ratio (RR) of 1.67（95％CI: 0.90-­3.10).

Conclusion: The incidence of hypocalcemia was increased in denosumab-exposed patients compared with non-exposed patients with RA in this observational study utilizing data from MID-­NET^®. As the adjusted RR of hypocalcemia with denosumab was modest, current risk management strategies outlined in the package insert are appropriate.

本資料は，AMED 医薬品等規制調和・評価研究事業「リアルワールドエビデンスの薬事制度下での利活用促進と国際規制調和に向けての課題整理と国内におけるあるべき体制の提言に向けた研究」班（研究代表者：中村治雅 国立研究開発法人 国立精神・神経医療研究センター）の分担研究課題として，日本製薬工業協会に加盟する製薬会社を対象に実施されたアンケート調査結果を報告する．医薬品におけるコンパニオンアプリ（Companion Application：CP）の開発とデータの利活用の実態を明らかにした国内初の調査であり，今後の医薬品のCP 開発と利用が普及し，CP によって収集された患者報告アウトカム（Patient-Reported Outcome：PRO）によるリアルワールドデータ（Real-World Data：RWD）の薬事行政下での利活用が期待される中で，本調査結果が，その促進に資する情報として一助になることを期待し，「資料」という形式で，アンケート調査結果の全部を公開する．