Does the Use of Denosumab in Combination with bDMARDs or tsDMARDs Increase the Risk of Infection in Patients with...

Background/Objectives: The combination of denosumab treatment with biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) in patients with inflammatory rheumatic diseases (IRD) may raise safety concerns for clinicians, particularly regarding infections. In this study, we investigated whether the risk of infection increases in patients who receive bDMARDs or tsDMARDs for IRD and are simultaneously treated with denosumab for osteoporosis (OP). Methods: As a control group, we evaluated patients receiving bDMARDs or tsDMARDs concomitantly with zoledronic acid (ZA), which is not clearly associated with infections. A total of 88 patients-including 30 patients receiving bDMARDs or tsDMARDs with ZA and 58 patients receiving bDMARDs or tsDMARDs with denosumab-met the criteria and were included in this study. The groups were compared in terms of the ratio/risk of serious infections requiring hospitalisation and infections requiring outpatient treatment after applying the inverse probability of treatment weighting (IPTW) to the control for confounding factors. The Cox proportional hazards regression model was used to compare the risks of infection, taking confounding factors into account. Results: The mean age of patients in the ZA group was 59.07 years (±SD: 13.65), while that of patients in the denosumab group was 69.93 years (±SD: 11.72). Comorbidities occurred more frequently in the denosumab group (n = 44, 75.86%) than in the ZA group (n = 14, 46.66%). The median duration of medication use in the denosumab group was 24 months (minimum: 6 months; maximum: 72 months). The median duration of medication use in the ZA group was 24 months (minimum: 12 months; maximum: 60 months). When comparing the groups regarding the risk of infection, denosumab was not associated with an increased risk of either a serious infection requiring hospitalisation (Hazard Ratio (HR): 0.37; 95% Confidence Interval (CI): 0.14-0.94) or an infection requiring outpatient treatment (HR: 0.29; 95% CI: 0.12-0.71). Conclusions: In conclusion, the combination of denosumab treatment with bDMARD or tsDMARD treatments is safe for short-term use.