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Does denosumab exert a protective effect against COVID-19? Results of a large cohort study
Sara Cassibba1, Silvia Ippolito1, Silvia Pellegrini1,2
1Endocrinology and Diabetes Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
Insights
Denosumab treatment was associated with a lower incidence of symptomatic COVID-19, especially in elderly patients. This suggests denosumab can be safely continued during the pandemic, potentially offering a protective effect against infection.
Area of Science:
- Immunology
- Infectious Diseases
- Endocrinology
Background:
- Denosumab, a RANK/RANKL inhibitor, impacts osteoclastogenesis and immune activation.
- The role of denosumab in infectious disease response, including COVID-19, requires investigation.
Purpose of the Study:
- To explore the relationship between denosumab treatment and the occurrence and severity of COVID-19.
- To assess the safety of continuing denosumab in patients with COVID-19.
Main Methods:
- Retrospective cohort study comparing denosumab-treated patients with controls.
- Multivariate logistic regression analysis to assess the association between denosumab and COVID-19, adjusting for confounders.
- Subgroup analyses based on age, sex, BMI, smoking status, and vitamin D levels.
Main Results:
- Lower COVID-19 incidence in the denosumab group (7.6% vs. 14.6%, p=0.004).
- No significant difference in COVID-19 severity between groups.
- Denosumab associated with reduced symptomatic COVID-19 (OR 0.46, p=0.049), particularly in patients over 75 years (OR 0.12, p=0.011).
Conclusions:
- Denosumab treatment appears safe for COVID-19 patients.
- RANK/RANKL inhibition by denosumab is associated with a reduced incidence of symptomatic COVID-19.
- A potential protective effect of denosumab against COVID-19 is suggested, especially in the elderly population.
Introduction:
Denosumab is a monoclonal antibody blocking the receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand (RANK/RANKL) pathway, thus inhibiting osteoclastogenesis. Since RANK and RANKL are also involved in the immune system activation, denosumab might interfere with the response against infections. Our study aimed to explore the relationship between denosumab treatment and coronavirus disease 2019 (COVID-19).
Design And Methods:
The occurrence and severity of COVID-19 were recorded in consecutive patients referred to the Endocrinology Department of Papa Giovanni XXIII Hospital, Bergamo, from 1 January 2020 to 1 January 2021. Patients treated with denosumab were compared to outpatient controls. Patients' features were summarized by descriptive statistics. Multivariate logistic regression assessed the relationship between denosumab and COVID-19, adjusting for potential confounders. Subgroup analyses according to age, sex, body mass index (BMI), smoking status, and vitamin D levels were performed.
Results:
The final population included 331 patients treated with denosumab and 357 controls. COVID-19 incidence was lower in the denosumab group (7.6% vs. 14.6%, p = 0.004). COVID-19 severity was similar in both groups. Multiple logistic regression confirmed an association between denosumab and a reduced occurrence of symptomatic COVID-19 [odds ratio (OR) 0.46, 95% CI 0.21-0.98, p = 0.049]. Subgroup analyses suggested a potential protective effect of denosumab in patients over 75 years (OR 0.12, 95% CI 0.02-0.6, p = 0.011), with a significant interaction between denosumab and age categories (p = 0.047).
Conclusion:
Our study confirms that denosumab may be safely continued in COVID-19 patients. RANK/RANKL inhibition seems associated with a reduced incidence of symptomatic COVID-19, particularly among the elderly.
