Risk of Hospitalized Bacterial Infections Associated With Biologic Treatment Among US Veterans With Rheumatoid Arthritis

Authors

  • J. R. Curtis,

    Corresponding author
    1. University of Alabama at, Birmingham
    • University of Alabama at Birmingham, Faculty Office Towers 802, 510 20th Street South, Birmingham, AL 35294. E-mail: jcurtis@uab.edu

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    • Dr. Curtis has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, BMS, Crescendo, UCB, and AbbVie, and (more than $10,000 each) from Roche/Genentech, Janssen, CORRONA, and Amgen.

  • S. Yang,

    1. University of Alabama at, Birmingham
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  • N. M. Patkar,

    1. University of Alabama at, Birmingham
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  • L. Chen,

    1. University of Alabama at, Birmingham
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  • J. A. Singh,

    1. University of Alabama at Birmingham and VA Medical Center, Birmingham, Alabama
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    • Dr. Singh has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Savient, Regeneron, URL Pharmaceuticals, Ardea, Allergan, and Novartis, and (more than $10,000) from Takeda, and has received investigator-initiated grants from Takeda and Savient.

  • G. W. Cannon,

    1. VA Medical Center, Salt Lake City, Utah
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  • T. R. Mikuls,

    1. Omaha VA Medical Center, Omaha, Nebraska
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    • Dr. Mikuls has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Genentech and Roche.

  • E. Delzell,

    1. University of Alabama at, Birmingham
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    • Dr. Delzell has received research support from Amgen.

  • K. G. Saag,

    1. University of Alabama at, Birmingham
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    • Dr. Saag has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Abbott, BMS, Roche, and AbbVie.

  • M. M. Safford,

    1. University of Alabama at, Birmingham
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  • S. DuVall,

    1. VA Medical Center and University of Utah, Salt Lake City
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    • Dr. Duvall has received research grants from Amgen, Anolinx, Genentech, Merck, Mylan Specialty, Roche, Shire, and Hoffman-La Roche.

  • K. Alexander,

    1. Genentech, South San Francisco, California
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    • Dr. Alexander owns stock and/or stock options in Genentech/Roche.

  • P. Napalkov,

    1. Genentech, South San Francisco, California
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    • Dr. Napalkov is a shareholder of Hoffmann-La Roche/Genentech.

  • Kevin L. Winthrop,

    1. Oregon Health Sciences University, Portland
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    • Dr. Winthrop has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from UCB, Genentech, Regeneron, BMS, and AbbVie, and (more than $10,000) from Pfizer.

  • M. J. Burton,

    1. G. V. Sonny Montgomery VA Medical Center, Jackson, Mississippi
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  • A. Kamauu,

    1. Anolinx, Salt Lake City, Utah
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    • Dr. Kamauu owns stock and/or stock options in Anolinx, has received research grants from Genentech, and has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Roche, Shire, and Dey Pharma.

  • J. W. Baddley

    1. University of Alabama at Birmingham and VA Medical Center, Birmingham, Alabama
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    • Dr. Baddley has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, Abbott, and Merck.


Abstract

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.

Conclusion

In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.

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