Background Patients with autoimmune diseases are at increased risk of early onset osteoporosis due to multiple reasons including prolonged exposure to corticosteroids and the disease process itself in RA patients. Same patients are more likely to be on TNF inhibitors or other biologics, which causes them to be at an increased risk of infections. Denosumab, an anti-RANK ligand inhibitor, itself a biologic, used to treat osteoporosis, is associated with increased infection risk as Receptor activator of nuclear factor kappa B ligand (RANKL) is also expressed on activated T and B lymphocytes (1). It is unknown if there is an added risk of infections when TNF inhibitors/biologic agents and denosumab are used concomitantly.
Objectives To determine if denosumab and biologics are associated with increased infection risk.
Methods Data was collected and analyzed on 40 patients in the rheumatology clinic who had been on denosumab and TNF inhibitor/ other biologic for 66 months at the Keck Medical Center of USC.
Results Patient characteristics: Mean age: 70±9.8 SD years, Gender: 98% were females, 2% Males. 75% had RA, 10% SLE, 15% had other rheumatic diseases. 70% on TNF inhibitors, 30% on other biologics. Before Denosumab (over 2 years): cumulative infection rate 17.5%, which is 8.75 cases per 100 person-years. 9% hospitalization rate. Post Denosumab: After 12 months: No infections within the first year. After 60 months: incidence rate of infections=12.5 cases/100 person-years. After 66 months, incidence rate of infections=15.9 cases/100 person-years. Urinary tract infection (UTI) accounted for the most common infection (17.5%). No opportunistic infections, and no reactivation of latent TB found in our patients.
Conclusions No infections developed within the first year, suggesting a cumulative effect of increased infection risk, if any. We cannot attribute the overall infection rate solely to the combination of denosumab and biologics as patients who developed infections either had Diabetes Mellitus, urinary incontinence, recent surgery, underlying pulmonary disease. Patients did not develop infections beyond what would be expected for their comorbidities and medications. Whether prophylactic antibiotics are indicated in patients with recurrent infections PRIOR to denosumab is uncertain, but may be a consideration in certain patients.
Cummings SR, San Martin J, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765. doi: 10.1056/NEJMoa0809493.
Disclosure of Interest None declared