Initiation of tumor necrosis factor-αantagonists and the risk of hospitalization for infection in patients with autoimmune diseases

Carlos G. Grijalva, Lang Chen, Elizabeth Delzell, John W. Baddley, Timothy Beukelman, Kevin Winthrop, Marie R. Griffin, Lisa J. Herrinton, Liyan Liu, Rita Ouellet-Hellstrom, Nivedita M. Patkar, Daniel H. Solomon, James D. Lewis, Fenglong Xie, Kenneth G. Saag, Jeffrey R. Curtis

Research output: Contribution to journalArticle

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Abstract

Context: Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. Objectives: To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization. Design, Setting, and Patients: Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. Main OutcomeMeasure: Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens. Results: Study cohorts included 10 484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Conclusion: Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.

Original languageEnglish (US)
Pages (from-to)2331-2339
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume306
Issue number21
DOIs
StatePublished - Dec 7 2011

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Autoimmune Diseases
Hospitalization
Tumor Necrosis Factor-alpha
Infection
Psoriasis
Spondylarthropathies
Rheumatoid Arthritis
Inflammatory Bowel Diseases
Medicaid
Glucocorticoids
Propensity Score
Soft Tissue Infections
Psoriatic Arthritis
Ankylosing Spondylitis
Medicare
Proportional Hazards Models
Pneumonia
Cohort Studies
Safety
Skin

ASJC Scopus subject areas

  • Medicine(all)

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Initiation of tumor necrosis factor-αantagonists and the risk of hospitalization for infection in patients with autoimmune diseases. / Grijalva, Carlos G.; Chen, Lang; Delzell, Elizabeth; Baddley, John W.; Beukelman, Timothy; Winthrop, Kevin; Griffin, Marie R.; Herrinton, Lisa J.; Liu, Liyan; Ouellet-Hellstrom, Rita; Patkar, Nivedita M.; Solomon, Daniel H.; Lewis, James D.; Xie, Fenglong; Saag, Kenneth G.; Curtis, Jeffrey R.

In: JAMA - Journal of the American Medical Association, Vol. 306, No. 21, 07.12.2011, p. 2331-2339.

Research output: Contribution to journalArticle

Grijalva, CG, Chen, L, Delzell, E, Baddley, JW, Beukelman, T, Winthrop, K, Griffin, MR, Herrinton, LJ, Liu, L, Ouellet-Hellstrom, R, Patkar, NM, Solomon, DH, Lewis, JD, Xie, F, Saag, KG & Curtis, JR 2011, 'Initiation of tumor necrosis factor-αantagonists and the risk of hospitalization for infection in patients with autoimmune diseases', JAMA - Journal of the American Medical Association, vol. 306, no. 21, pp. 2331-2339. https://doi.org/10.1001/jama.2011.1692
Grijalva, Carlos G. ; Chen, Lang ; Delzell, Elizabeth ; Baddley, John W. ; Beukelman, Timothy ; Winthrop, Kevin ; Griffin, Marie R. ; Herrinton, Lisa J. ; Liu, Liyan ; Ouellet-Hellstrom, Rita ; Patkar, Nivedita M. ; Solomon, Daniel H. ; Lewis, James D. ; Xie, Fenglong ; Saag, Kenneth G. ; Curtis, Jeffrey R. / Initiation of tumor necrosis factor-αantagonists and the risk of hospitalization for infection in patients with autoimmune diseases. In: JAMA - Journal of the American Medical Association. 2011 ; Vol. 306, No. 21. pp. 2331-2339.
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abstract = "Context: Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. Objectives: To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization. Design, Setting, and Patients: Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. Main OutcomeMeasure: Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens. Results: Study cohorts included 10 484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53{\%}) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95{\%} CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95{\%} CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95{\%} CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95{\%} CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95{\%} CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Conclusion: Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.",
author = "Grijalva, {Carlos G.} and Lang Chen and Elizabeth Delzell and Baddley, {John W.} and Timothy Beukelman and Kevin Winthrop and Griffin, {Marie R.} and Herrinton, {Lisa J.} and Liyan Liu and Rita Ouellet-Hellstrom and Patkar, {Nivedita M.} and Solomon, {Daniel H.} and Lewis, {James D.} and Fenglong Xie and Saag, {Kenneth G.} and Curtis, {Jeffrey R.}",
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T1 - Initiation of tumor necrosis factor-αantagonists and the risk of hospitalization for infection in patients with autoimmune diseases

AU - Grijalva, Carlos G.

AU - Chen, Lang

AU - Delzell, Elizabeth

AU - Baddley, John W.

AU - Beukelman, Timothy

AU - Winthrop, Kevin

AU - Griffin, Marie R.

AU - Herrinton, Lisa J.

AU - Liu, Liyan

AU - Ouellet-Hellstrom, Rita

AU - Patkar, Nivedita M.

AU - Solomon, Daniel H.

AU - Lewis, James D.

AU - Xie, Fenglong

AU - Saag, Kenneth G.

AU - Curtis, Jeffrey R.

PY - 2011/12/7

Y1 - 2011/12/7

N2 - Context: Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. Objectives: To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization. Design, Setting, and Patients: Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. Main OutcomeMeasure: Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens. Results: Study cohorts included 10 484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Conclusion: Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.

AB - Context: Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. Objectives: To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization. Design, Setting, and Patients: Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. Main OutcomeMeasure: Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens. Results: Study cohorts included 10 484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Conclusion: Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.

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