Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis.
OBJECTIVE
The comparative risk of infection associated with non-anti-tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA).


METHODS
Using 1998-2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders.


RESULTS
Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1-6.4) for rituximab, 2.8 (95% CI 1.7-4.7) for abatacept, and 3.0 (95% CI 2.5-3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9-2.2), abatacept (HR 1.1, 95% CI 0.6-2.1), or rituximab (HR 1.4, 0.8-2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3-4.0). Infection risk was greater for those taking prednisone >7.5 mg/day (HR 1.8, 95% CI 1.3-2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4-3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3-7.2) compared to the lowest quartile.


CONCLUSIONS
In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.
University of Alabama at, Birmingham.
J R
JR
Curtis
S
S
Yang
N M
NM
Patkar
L
L
Chen
J A
JA
Singh
G W
GW
Cannon
T R
TR
Mikuls
E
E
Delzell
K G
KG
Saag
M M
MM
Safford
S
S
DuVall
K
K
Alexander
P
P
Napalkov
Kevin L
KL
Winthrop
M J
MJ
Burton
A
A
Kamauu
J W
JW
Baddley
D000069594:Abatacept; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology; D001424:Bacterial Infections / Q000453:epidemiology / Q000209:etiology*; D015897:Comorbidity; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D006760:Hospitalization; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014481:United States / Q000453:epidemiology; D014728:Veterans / Q000706:statistics & numerical data
D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept