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.

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.