Researchers Find Low Infection Risk With Denosumab Plus Other Biologics

Rheumatoid arthritis (RA) is associated with a number of comorbidities, including osteoporosis. The known risk of bone loss in patients with RA lead physicians to prescribe additional therapies, such as oral bisphosphonates or denosumab, for osteoporosis. A recent study, published in The Journal of Rheumatology, was conducted to determine whether the concurrent use denosumab with a biologic disease-modifying antirheumatic drug (bDMARD), such as adalimumab, etanercept, or infliximab, increases the risk of infection.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor-xB ligand (RANKL) and blocks the interaction of RANKL with its receptor on the surface of osteoclasts and osteoclast precursors. This leads to a reduction in osteoclast number and activity, a decrease in bone resorption, an increase in bone mass, and a reduction in vertebral and nonvertebral fracture risk.

RANKL is expressed in activated T and B lymphocytes and in lymph nodes; therefore, there is a hypothetical possibility that denosumab may increase the risk of infections due to the inhibition of the RANK pathway. Previous studies have suggested that exposure to multiple biologic agents, each carrying an independent elevated risk of infection, may be associated with an even higher risk of infection.

The study’s participants were chosen from patients from 2 academic rheumatology practices in Canada between July 1, 2010 and July 31, 2014. The medical records from these rheumatology practices during the designated time period included about 3000 patients taking bDMARD therapy. Eligible patients for the study fit into the following criteria: 18 years or older with an RA diagnosis, received 1 or more injection or infusion, or filled a prescription for a bDMARD for RA during the study period.

Patients in the concurrent therapy group (n = 102) were required to have a moderate to high risk of fracture and to have received 1 or more injection of denosumab while taking a bDMARD.

Conversely, patients in the bDMARD-only group (n = 206) never received denosumab during the study period. The patients in the concurrent group were matched 1:2 to patients receiving solely a bDMARD.

There were 3 serious infection events reported in the concurrent group, and 4 serious infection events and 1 opportunistic infection event reported in the bDMARD-only group. The most commonly reported type of infection was pneumonia. The rates of serious or opportunistic infections were 1.22 per 100 patient-years (95% confidence interval [CI]; range, —0.25 to 3.56) in the concurrent group and 0.98 per 100 patient-years (95% CI; range, 0.32 to 2.29) in the bDMARD-only group, with a rate difference of 0.24.

The study showed that the occurrence of serious infections was low in patients with RA treated concurrently with a bDMARD and denosumab, and in patients treated with a bDMARD alone. This data should encourage patients that their drug regimen is unlikely to cause infections or other illnesses.