Denosumab Does Not Increase Infection Risk in Rheumatic Disease Patients When Used Alone or in Combination with Biologic DMARDs


Newswise — BOSTON — Patients with rheumatic diseases who are treated with denosumab (Prolia®, Xgeva®) either alone, or in combination with either biologic or non-biologic disease-modifying antirheumatic drugs (DMARDs), do not appear to have a significant increased risk of infections, according to new research presented this week at the American College of Rheumatology Annual Meeting in Boston.

People with a number of rheumatic diseases use DMARDs to treat their inflammation and help control disease activity, including rheumatoid arthritis, or RA. Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling and limitation in the motion and function of multiple joints. Although joints are the principal body parts affected by RA, inflammation may develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Due to their immunosuppressant mechanisms, biologic DMARDs, may increase the risk of infection in rheumatic disease patients. It is unknown if denosumab, a RANK-ligand inhibitor used in the treatment of osteoporosis, also increases infection susceptibility. RANK is a member of the tumor necrosis factor receptor (TNFR) superfamily, so may also suppress the immune system. Past research has showed an increase in cellulitis and erysipelas in patients on denosumab.

To find out if denosumab increased infection risk in rheumatic disease patients, researchers at Drexel University College of Medicine in Philadelphia culled retrospective data from chart reviews of patients in specialty rheumatology practice to evaluate infection rates and hospitalizations of 136 patients: 36 on a combination of biologics and denosumab, 50 on biologic agents alone and 50 on denosumab alone. The biologics studied included infliximab (Remicade®), tocilizumab (Actemra®), rituximab (Rituxan®), belimumab (Benlysta®), abatacept (Orencia®), adalimumab (Humira®) and golimumab (Simponi®).

“The objective of the study was to evaluate whether denosumab with a biologic will increase risk of infection more than that from a biologic alone. We were also interested to see if addition of oral DMARDs and prednisone to denosumab would influence the risk of infection,” said Sajina Prabhakaran, MD of Drexel University in Philadelphia and a lead author of the study.

The researchers found no difference in infection risk between the groups that received both biologic and denosumab compared to biologics alone. There were statistically significant increases in the risk of infection in the groups that received both biologic and denosumab compared to the group that received denosumab only, as well as the group taking only a biologic compared to only denosumab.

Hospitalization rates were higher in the combination group compared to those taking only denosumab. There were statistically significant increases in the risk of infection with increased duration of exposure to biologics as well. Secondary characteristics also did not affect the compared rates of infection.

The study’s authors concluded that denosumab, taken either alone or in combination with biologics, does not significantly increase infection risk in rheumatic disease patients. Patients’ duration of exposure to denosumab also did not affect the infection rate. In addition, the authors noticed no increased risk of infection in patients on a combination of non-biologic DMARDs and denosumab. They concluded that it seems relatively safe to use denosumab in combination with other disease-modifying drugs to treat rheumatic disease patients.

“Although the safety profile of denosumab has been studied in the past and it has shown to be relatively safe with a slight increase in skin infections this is the first study to evaluate infection risk in combination with a biologic,” said Dr. Prabhakaran. “Our study showed no increase in the risk of infection in patients who received denosumab with a biologic over the patients who received a biologic alone. These results suggest that denosumab may be safely administered in patients with connective tissue diseases on biologics who already have an increased risk of metabolic bone disease.”

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The American College of Rheumatology is an international professional medical society that represents more than 9,500 rheumatologists and rheumatology health professionals around the world. Its mission is to Advance Rheumatology! The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official #ACR14 hashtag. Paper Number: 921

Sajina Prabhakaran, Drexel University College of Medicine, Philadelphia, PA and Charles Pritchard, Drexel University College of Medicine, Willow Grove, PA

Background/Purpose: Biologics including rituximab, abatacept and belimumab increase the risk of infection in patients. Denosumab, a RANK-ligand inhibitor used in the treatment of osteoporosis may theoretically make patients more susceptible to infections. RANK is a member of the tumor necrosis factor receptor (TNFR) superfamily so inhibition may cause immunosuppression. One pivotal trial showed an increase in cellulitis and erysipelas in patients on denosumab. We used a retrospective chart review of a patients in a sole specialty rheumatology practice to evaluate the infection rates and hospitalizations of patients on the combination of biologics with denosumab, biologic agents alone, and denosumab alone. Methods: We reviewed the charts of 136 patients, 50 patients who received biologics only, 50 patients who received denosumab alone and 36 patients who received both simultaneously over the past 4 years. Biologics studied included infliximab, tocilizumab, rituximab, belimumab, abatacept, adalimumab, and golimumab. The primary end-point was to determine if there was a greater risk of infection, hospitalization, complication or discontinuation of biologic and/ or denosumab in the combined group versus the biologic alone. Percentage of incidence was calculated for each group and Chi-square and Fisher’s Exact tests were used for analysis. Relative risks were calculated to compare infection risks between groups.

Results: There was no difference found in the risk of infection between the groups that received both biologic and denosumab compared to biologic alone, RR = 1.24, 95%, CI: 0.76 -2.04. There were statistically significant increases in the risk of infection in the groups that received both biologic and denosumab compared to the group that received denosumab; RR=7.87, 95% CI: 2.49-24.9 and biologic alone compared to denosumab, RR=6.33, 95% CI 2 - 20.1. Hospitalization rates were higher in the combination group compared to the denosumab (19.4% vs 12%, p=0.038). Statistically significant increases in the risk of infection with increased duration of exposure to biologics (p<0.001) were also noted.

Conclusion: We did not find an increased risk of infection with the combination of denosumab and a biologic compared to a biologic alone. The rates of infection and hospitalization of patients in the combination group were not significantly different between biologic medications.Secondary characteristics also did not affect the compared rates of infection.The duration of exposure to denosumab did not affect the infection rate. There did not seem to be any increased risk of infection in patients on combination non biologic DMARDs and denosumab. In summary this retrospective small study from a sole specialty rheumatology practice did not show a statistical increased risk of infection combining a biologic with denosumab vs a biologic. Hence it appears to be relatively safe to combine denosumab with a biologic agent.

Disclosures: S. Prabhakaran, None; C. Pritchard, Genetech, Abbvie.

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