POS1114 INFECTION RISK AMONG RHEUMATIC PATIENTS RECEIVING DENOSUMAB THERAPY: SINGLE CENTRE EXPERIENCE
Authors: K. L. Ng, M. Mohd Zain, I. S. Lau
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteoporosis (OS) is common in rheumatic diseasas (RMD). OS fracture leads to morbidity and premature mortality. The treatment for OS is well established with good long term safety profile. Oral bisphosphonate (BIS) is recommended as initial treatment option for both postmenopausal and glucocorticoid induced OS. Denosumab (DSB), is the noninferior alternative option. Despite its efficacy, DSB was linked with elevated infection risk in non RMD. Yet, data in RMD is lacking. Objectives: To determine the infection risk and associated factors in RMD patients receiving DSB. Methods: This is retrospective cohort study. Data was extracted from medical database (between Jan 2010 &amp; Dec 2018) at Selayang Hospital, Malaysia. Descriptive statistical analysis, logistic regression (LR) and cox (proportional hazard) regression [CPHR] were the analysis methods. Results: 50 cases were analysed. 96% were female. The median age was 72.5 ± 12.7 years. The primary rheumatological disorders were rheumatoid arthritis (48%), OS (24%) and systemic lupus erythematosus (10%). 92% had ≥ 1 comorbidity including metabolic/cardiovascular diseases (74%), chronic lung diseases (CLD) (40%) and diabetes mellitus (DM) (22%). 54% had disease modifying anti rheumatic drug (DMARD) therapy; majority (59.2%) received single conventional synthetic DMARD. Only 7.4% received combination biologic DMARD therapy. 28% had received prednisolone therapy, with dose &lt; 7.5mg OD in 78.6%. The median age at DSB initiation was 71 ± 12.4 years. 38% had fracture history and 88% had received previous OS treatment. In total, 13 infection episodes were recorded. The infection risk was 26% &amp; incidence rate was 134 cases per 1000 person-years. 84.6% required hospitalisation and 38.5% were severe cases. The mortality rate was 23.1%. The mean DSB treatment duration to first infection was 15.46 ± 11.9 months. Univariate LR showed infection risk and hospitalisation were higher with longer DSB treatment duration, OR 1.062 (95% CI: 1.010 - 1.117), p = 0.018) &amp; OR 1.057 (95% CI: 1.003 - 1.114, p = 0.037), respectively. These risks were lower in absence of steroid use, OR 0.2 (95% CI: 0.051 - 0.784, p = 0.021) and OR 0.215 (95% CI: 0.052 - 0.889, p = 0.034), respectively. Additionally, infection risk was lower in absence of CLD, OR 0.188 (95% CI: 0.048 - 0.742, p = 0.017) and hospitalisation was lower without concomitant DM, OR 0.050 (95% CI: 0.050 — 0.950, p = 0.043). Yet, multivariate LR did not infer the above predictions, after adjustment made for age, gender, rheumatological diseases, comorbidity, DMARD therapy and steroid dosing. For severe infection and case fatality, no predictive factors were identified. CPHR showed patients without steroid use had lower fatality risk, HR 0.077 (95% CI: 0.007 - 0.864, p = 0.038). With confounding factors (age, gender, previous infection and comorbidity), the observed difference was insignificant. Conclusion: Risk of infection and hospitalisation could be higher in rheumatic patients receiving longer DSB treatment duration. Concomitant comorbidities (CLD and DM) might increase the risk of infection and/or hospitalisation. References: [1]Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756–65. [2]Watts NB, Roux C, Modlin JF, Brown JP, Daniels A, Jackson S, Smith S, Zack DJ, Zhou L, Grauer A, Ferrari S. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int. 2012;23(1):327–337. [3]Prabhakaran S, Pritchard C. Comparison of infection rates in patients receiving denosumab, denosumab and biologics and biologics alone in a suburban rheumatology clinic [abstract]. Arthritis Rheumatol 2014;66 Suppl 10:S409. [4]Bray V, Bagley A, West S, Etzel C, Kremer J, Kolfenbach J. Infection risk among patients receiving concurrent denosumab and biologic or non-biologic DMARD therapy: An analysis of the Consortium Acknowledgements: We would like to thank the Director General of Health Malaysia for his permission for this poster presentation. Disclosure of Interests: None declared.