Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis

J. R. Curtis, S. Yang, N. M. Patkar, L. Chen, J. A. Singh, G. W. Cannon, T. R. Mikuls, E. Delzell, K. G. Saag, M. M. Safford, S. Duvall, K. Alexander, P. Napalkov, Kevin L. Winthrop, M. J. Burton, A. Kamauu, J. W. Baddley

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)990-997
Number of pages8
JournalArthritis Care and Research
Volume66
Issue number7
DOIs
StatePublished - Jul 2014

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Veterans
Bacterial Infections
Rheumatoid Arthritis
Confidence Intervals
Tumor Necrosis Factor-alpha
Biological Factors
Infection
Therapeutics
Veterans Health
United States Department of Veterans Affairs
Blood Sedimentation
Bacteremia
Prednisone
Urinary Tract
Proportional Hazards Models
C-Reactive Protein
Sepsis
Pneumonia
Hospitalization
Abatacept

ASJC Scopus subject areas

  • Rheumatology

Cite this

Curtis, J. R., Yang, S., Patkar, N. M., Chen, L., Singh, J. A., Cannon, G. W., ... Baddley, J. W. (2014). Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis. Arthritis Care and Research, 66(7), 990-997. https://doi.org/10.1002/acr.22281

Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis. / Curtis, J. R.; Yang, S.; Patkar, N. M.; Chen, L.; Singh, J. A.; Cannon, G. W.; Mikuls, T. R.; Delzell, E.; Saag, K. G.; Safford, M. M.; Duvall, S.; Alexander, K.; Napalkov, P.; Winthrop, Kevin L.; Burton, M. J.; Kamauu, A.; Baddley, J. W.

In: Arthritis Care and Research, Vol. 66, No. 7, 07.2014, p. 990-997.

Research output: Contribution to journalArticle

Curtis, JR, Yang, S, Patkar, NM, Chen, L, Singh, JA, Cannon, GW, Mikuls, TR, Delzell, E, Saag, KG, Safford, MM, Duvall, S, Alexander, K, Napalkov, P, Winthrop, KL, Burton, MJ, Kamauu, A & Baddley, JW 2014, 'Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis', Arthritis Care and Research, vol. 66, no. 7, pp. 990-997. https://doi.org/10.1002/acr.22281
Curtis, J. R. ; Yang, S. ; Patkar, N. M. ; Chen, L. ; Singh, J. A. ; Cannon, G. W. ; Mikuls, T. R. ; Delzell, E. ; Saag, K. G. ; Safford, M. M. ; Duvall, S. ; Alexander, K. ; Napalkov, P. ; Winthrop, Kevin L. ; Burton, M. J. ; Kamauu, A. ; Baddley, J. W. / Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis. In: Arthritis Care and Research. 2014 ; Vol. 66, No. 7. pp. 990-997.
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title = "Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis",
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.",
author = "Curtis, {J. R.} and S. Yang and Patkar, {N. M.} and L. Chen and Singh, {J. A.} and Cannon, {G. W.} and Mikuls, {T. R.} and E. Delzell and Saag, {K. G.} and Safford, {M. M.} and S. Duvall and K. Alexander and P. Napalkov and Winthrop, {Kevin L.} and Burton, {M. J.} and A. Kamauu and Baddley, {J. W.}",
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T1 - Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis

AU - Curtis, J. R.

AU - Yang, S.

AU - Patkar, N. M.

AU - Chen, L.

AU - Singh, J. A.

AU - Cannon, G. W.

AU - Mikuls, T. R.

AU - Delzell, E.

AU - Saag, K. G.

AU - Safford, M. M.

AU - Duvall, S.

AU - Alexander, K.

AU - Napalkov, P.

AU - Winthrop, Kevin L.

AU - Burton, M. J.

AU - Kamauu, A.

AU - Baddley, J. W.

PY - 2014/7

Y1 - 2014/7

N2 - 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.

AB - 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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