Background/Purpose:
Previous studies
combining immunosuppressive biologics have shown an increased risk of
infections. Few studies have examined the risk of infection with concurrent use
of the anti-osteoporosis agent, denosumab (DMAb), a human monoclonal antibody,
and an immunosuppressive biologic used to treat rheumatoid arthritis (RA). In
this study we examined the occurrence of serious and opportunistic infections
in two RA populations: patients treated concurrently with DMAb and an
immunosuppressive biologic, and patients treated with only an immunosuppressive
biologic.

Methods:
We reviewed a
select group of RA patients from two rheumatology
practices in Hamilton,
Ontario, Canada, between the study period of July 01, 2010 and July 31, 2014.
Patients were included if they were ≥ 18 years of age with RA, registered
in the treatment center ≥ 3 months before and after the index date, and
received ≥ 1 injection/infusion or filled a prescription for an
immunosuppressive biologic therapy for RA. Patients were excluded if they had
HIV or AIDS, were receiving cancer treatment or immunosuppressive therapies for
conditions other than RA, or were living in a nursing home. We examined two RA
patient groups: those who had used DMAb and an immunosuppressive biologic
concomitantly in the study period (concurrent group) and those who had used an
immunosuppressive biologic alone in the study period (biologic-alone group).
The concurrent group was assigned an index date derived from their initial DMAb
injection. A frequency-matching technique utilizing the index date of the
concurrent group was used to select the index date of the biologic-alone group.
Serious infection was defined as resulting in hospitalization or an ER visit
with use of IV antibiotics, associated with the primary diagnosis of infection.
Instances of serious or opportunistic infections were recorded. The
observational period for infections was between the index date and July 31,
2014 or loss to follow-up, whichever came first. As this was not a comparative
study, each group was analyzed separately.

Results:
A total of 218
patients met eligibility criteria for the study (N = 109 concurrent group; N =
109 biologic-alone group). Descriptive statistics for both groups are provided
in Table 1. Three events of serious infection occurred in three patients in the
concurrent group (three cases of pneumonia resulting in hospitalization), and
three events of serious infection occurred in three patients in the
biologic-alone group (two cases of pneumonia and one upper respiratory tract
infection, all resulting in hospitalization). In both groups, all patients
recovered and there were no instances of opportunistic infections or death.

Conclusion:
RA patients may
require treatment for bone loss due to intrinsic disease, steroid use, and
advancing age. This study demonstrates a low occurrence of serious infections
in biologically-treated RA patients, including patients with concurrent DMAb use.