ACR Boston 2014 | Daily Highlights

Comparison of Infection Rates in Patients Receiving Denosumab, Denosumab and Biologics and Biologics Alone in a Suburban Rheumatology Clinic

Background:
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.

Conclusions:
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.

Disclosure of Interest:
S. Prabhakaran, None; C. Pritchard, Genetech, Abbvie, 6.

Comment:
Das Abstract zeigt einerseits, was wir schon wissen: Die Infektionsrate unter Biologika ist gegenüber Patienten ohne Biologika oder nur konventionellen DMARDs deutlich erhöht. Hingegen scheint die zusätzliche Gabe von Denosumab die Infektionsgefahr nicht weiter zu erhöhen. Auch Denosumab allein führte nicht zu vermehrten Infekten. Eingeschränkt wird die Aussagekraft der Resultate durch die relativ geringe Patientenzahl (total 136 Patienten) und die Tatsache, dass die Patienten nur von einem einzigen Zentrum rekrutiert wurden. Es werden zudem keine Informationen zum Infektionsscreening der Patienten vor der Therapie gegeben.

Fazit:
Bei Vorliegen einer Osteoporose bei Patienten unter einer Biologikatherapie scheint Denosumab eine sichere Alternative zu anderen Antiresorptiva zu sein. Wegen der bereits durch die Biologikabehandlung alleine erhöhten Infektionsgefahr sind die Patienten jedoch vor Einleiten einer Therapie bezüglich vorbestehender Infektionen abzuklären und im Verlauf der Therapie regelmässig zu überwachen.

Zusammenfassung und Kommentar von:
Dr. med. Diana Frey
UniversitätsSpital Zürich