Background/Purpose:

Patients with RA and other rheumatologic disorders are at increased risk for osteoporotic fractures. Biologic DMARDs are an important treatment option for these patients. However, they are associated with increased infection risk. It is well known that combining biologic DMARDs increases the risk of serious adverse effects, including infections. Considering its mechanism of action, there has been concern that denosumab (Dmab) may increase infection risk when combined with biologic DMARDs. Here we report the results of a retrospective chart review in an outpatient rheumatology practice that evaluated and compared the rates of serious infections in patients receiving Dmab alone, biologic DMARDs alone, Dmab with biologic DMARDs, and bisphosphonates with biologic DMARDs.

Methods:

We performed a retrospective chart review of 389 patients, of whom 159 received Dmab alone, 193 biologic DMARD alone, 10 Dmab + biologic DMARD, and 27 bisphosphonate + biologic DMARD.  Data were collected from Jan 2010 through May 2015. The primary endpoint was to compare the rate of serious infections in the Dmab + biologic DMARD group to the biologic DMARD alone group. Rates were calculated for each group and then compared. Chi-square test and relative risk estimates were used for statistical analysis. 95% CI and P values were calculated for each group.  

Results:

The Dmab + biologic DMARD group had a higher rate of serious infections compared to the biologic DMARD alone group (RR=12, 95%CI 2.41-68.52, P=0.002). The rate of serious infections for the Dmab + biologic DMARD group was also significantly higher compared to the Dmab alone group (RR=10.60; 95% CI:1.99-56. P=0.005). No difference in serious infections was observed between the Dmab + biologic DMARD and bisphosphonate + biologic DMARD groups (RR 1.80, 95% CI 0.35-9.2 P=0.48). The Dmab + biologic DMARD group was older (76; SD 7.7) than the biologic DMARD alone group (56; SD 16), and bisphosphonate + biologic DMARD group (63; SD 10), but similar to the Dmab alone group (77; SD 9.9). Gender was female predominant in all 4 groups, 94% in Dmab alone, 100% in Dmab + biologic DMARD, 68% in biologic DMARD alone, and 88% in bisphosphonate + biologic DMARD. The types of serious infections requiring hospitalization were not significantly different between the 4 groups. These included community acquired pneumonia (n=3), post surgical wound infection (n=1), infectious bursitis (n=1), skin and soft tissue infections (SSTI) (n=2), Lyme disease (n=1), and Chikungunya (n=1). 

Conclusion:

We observed a greater rate of serious infections in patients receiving combination treatment with Dmab + biologic DMARD compared to biologic DMARD alone and to Dmab alone. The Dmab + biologic DMARD group was older compared to biologic DMARD alone group, which may contribute to the higher rate of serious infections observed. No other significant differences were observed among the 4 treatment groups, including duration of exposure. In summary, the findings of this retrospective study suggest that combination treatment with denosumab and biologic DMARD may increase the risk of serious infections, particularly in an older patient population. Caution should be exercised when considering combination therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/combination-therapy-with-denosumab-and-biologic-dmard-associated-with-higher-risk-of-serious-infections-compared-to-denosumab-alone-and-biologic-dmard-alone/