Background Patients with autoimmune diseases are at increased risk of early onset osteoporosis because of prolonged exposure to corticosteroids. RA patients may also develop early-onset osteoporosis secondary to the disease process itself. Same patients are more likely to be on TNF inhibitors or other biologics which cause them to be at an increased risk of infections. Denosumab is an anti-RANK ligand inhibitor used to treat osteoporosis. Receptor activator of nuclear factor kappa-B ligand (RANKL) is also expressed on activated T and B lymphocytes. Therefore, a RANKL inhibitor such as denosumab may increase the risk of infections.(1) In the Freedom Trial, the denosumab group reported more serious infections leading to hospitalization than in the placebo group.(1) It is unknown if biologic agents will increase the risk of infections when denosumab is used concomitantly.
Objectives To determine rate of infections in patients on combination therapy with denosumab and either TNF inhibitors or other biologics.
Methods We identified 40 patients in the rheumatology clinic on denosumab and either a TNF inhibitor or a biologic agent for 1 to 4 years. A retrospective chart review was conducted at the Keck Medical Center of USC to record if the patients developed infections.
Results The mean age of the population was 65 ± 20 years, among which 98% were females. 75% had Rheumatoid Arthritis (RA), 10% Systemic lupus erythematosus (SLE), 2.5% SLE and Sjogren's, 2.5% SLE with Antiphospholipid Syndrome (APLS), 2.5% RA and SLE, 2.5% Microscopic Polyangiitis, 2.5% Psoriatic arthritis, and 2.5% Neurologic Behcet's disease. Prior to initiation of denosumab, patients either failed bisphosphonate therapy or became intolerant. The addition of denosumab showed a trend of improvement of T scores in lumbar spine and hip. 40% of our patients developed some infection, which is lower than 52.9% in the FREEDOM trial.(1) 70% (28/40) patients were on TNF inhibitors. 35% of these developed infections. 30% (12/40) patients were on other biologic agents. 50% of these patients developed infections. Urinary tract infection (UTI) accounted for the most common infection (12%). 12% of our patients required hospitalization for infections, compared to 4% in the Freedom trial. 17.5% of these had developed infections before denosumab. 9% had been hospitalized before denosumab for infections.
Conclusions In conclusion, data from this study demonstrates that 40% patients developed infections. However, 17.5% of patients who developed infections in our study had developed infections before starting denosumab. It is therefore unclear weather the overall infection rate can be attributed solely to the combination of denosumab and biologics. Since we did not see any infections within the first year, there may be a cumulative effect of increased infection risk, if any. Antibiotic prophylaxis, while on denosumab and biologics, may be considered in patients with recurrent infections in the past.
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 P. Chhibar: None declared, G. Ehresmann Speakers bureau: Pfizer, Abbott, Takeda Pharmaceuticals, Genentech, Endo Pharmaceuticals and Amgen.