BOSTON -- The addition of denosumab (Prolia, ), an osteoporosis drug, to the treatment regimen of rheumatoid arthritis patients does not increase infection risk, whether it is administered alone or in combination with a biological disease-modifying rheumatic drugs (DMARDs), new research shows.
"There was no statistically significant difference in the overall rates of infection in patients who received denosumab with a biological disease modifying agent compared to a biological DMARD alone," said lead author a rheumatology fellow at in Philadelphia.
Action Points
- Note that these studies were published abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Serious infections, discontinuations, and hospitalizations were also no different between these groups, she added during a press conference at .
"This is something which is new. No one has looked at the biological DMARDs and denosumab combination and risk of infection, and in this small setting we did not find a raised risk of infection," said Prabhakaran, explaining that because DMARDs may already raise the risk of infection due to their immunosuppressive effects, there have been some concerns that denosumab, a RANK-ligand inhibitor, might increase this further.
A pivotal study of denosumab, the , offered the first hint of infection risk showing that denosumab was associated with an increased rate of severe skin infections such as cellulitis compared with placebo.
The current study retrospectively reviewed the charts of 136 patients at a suburban rheumatology center to assess the risk of infection in patients taking denosumab alone or in combination with DMARDs.
A total of 50 patients were taking denosumab alone (60 mg every 6 months), 50 were taking DMARDs alone, and 36 were taking both.
The DMARDs included infliximab (Remicade), tocilizumab (Actemra), rituximab (Rituxan), belimumab (Benlysta), abatacept (Orencia), adalimumab (Humira), and golimumab (Simponi).
The primary endpoint was the rate of infection, hospitalization, complication or discontinuation of biologic and/or denosumab in patients taking denosumab alone or combined with a DMARD.
The study found that denosumab in combination with a biologic, was not associated with increased infection rates compared with a biologic alone (relative risk [RR] 1.24, 95% CI 0.76-2.04).
However, patients who took denosumab alone had much lower infection risks than those who took biologics alone (RR 6.33, 95% CI 2-20.1) or a combination of biologic and denosumab (RR 7.87, 95% CI 2.49-24.9).
Hospitalization rates were also higher among patients who took combination therapy compared with those on denosumab alone (19.4% versus 12%, P=0.038).
There were discontinuations in 12% of DMARD patients, 17% of patients on combination therapy, and none of the patients on denosumab alone.
"These results suggest that denosumab may be safely administered in patients with connective tissue disease on biologics who already have an increased risk of metabolic bone disease," she noted.
A postmarketing safety surveillance study of denosumab, which was also presented at the meeting by the manufacturer and included 1,963,794 patient-years of exposure, suggested that the rate of overall serious infections associated with the drug "has decreased over time since product registration" (153 cases/100,000 patient-years in 2010 versus 57 cases/100,000 patient-years in 2014), and that cumulative reporting rates of serious infections "were low and below the background rates estimated from insurance claims data."
Disclosures
Prabhakaran disclosed no conflicts of interest.
Her co-author Dr. Charles Pritchard acknowledged relationships with Genentech and AbbVie.
Primary Source
American College of Rheumatology
Source Reference: Prabhakaran S, Pritchard C "Comparison of infection rates in patients receiving denosumab, denosumab and biologics and biologics alone in a suburban rheumatology clinic" ACR 2014; Abstract 921.