Anti–tumor necrosis factor α therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis

Authors

  • Sebastian Schneeweiss,

    Corresponding author
    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
    • Harvard Medical School, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, 1620 Tremont Street, Suite 3030, Boston, MA 02120
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    • Dr. Schneeweiss has received research grants from Pfizer and Merck. Dr. Weinblatt has received consulting fees from Abbott (more than $10,000) as well as from Amgen, Astra-Zeneca, Biogen, Bristol-Myers Squibb, Centocor, Genentech, Eli Lilly, Millennium Pharmaceuticals, Novartis, Roche, Sanofi-Aventis, Serona, Wyeth, and UCB (less than $10,000 each). Dr. Solomon has received research grants from Merck, Pfizer, and Savient.

  • Soko Setoguchi,

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Michael E. Weinblatt,

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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    • Dr. Schneeweiss has received research grants from Pfizer and Merck. Dr. Weinblatt has received consulting fees from Abbott (more than $10,000) as well as from Amgen, Astra-Zeneca, Biogen, Bristol-Myers Squibb, Centocor, Genentech, Eli Lilly, Millennium Pharmaceuticals, Novartis, Roche, Sanofi-Aventis, Serona, Wyeth, and UCB (less than $10,000 each). Dr. Solomon has received research grants from Merck, Pfizer, and Savient.

  • Jeffrey N. Katz,

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Jerry Avorn,

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Paul E. Sax,

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Raisa Levin,

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Daniel H. Solomon

    1. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
    • Dr. Schneeweiss has received research grants from Pfizer and Merck. Dr. Weinblatt has received consulting fees from Abbott (more than $10,000) as well as from Amgen, Astra-Zeneca, Biogen, Bristol-Myers Squibb, Centocor, Genentech, Eli Lilly, Millennium Pharmaceuticals, Novartis, Roche, Sanofi-Aventis, Serona, Wyeth, and UCB (less than $10,000 each). Dr. Solomon has received research grants from Merck, Pfizer, and Savient.


Abstract

Objective

To assess the association between the initiation of anti–tumor necrosis factor α (anti-TNFα) therapy and the risk of serious bacterial infections in routine care.

Methods

This was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti-TNFα therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization.

Results

The incidence of serious bacterial infections was, on average, 2.2 per 100 patient-years in this population (95% confidence interval [95% CI] 2.0–2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5–3.1]), with a clear dose-response relationship for dosages >5 mg/day (for ≤5 mg/day, RR 1.34; for 6–9 mg/day, RR 1.53; for 10–19 mg/day, RR 2.97; and for ≥20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti-TNFα therapy (RR 1.0 [95% CI 0.6–1.7]) or other DMARDs as compared with initiators of MTX.

Conclusion

In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFα therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.

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