Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis.
OBJECTIVE
To assess the association between the initiation of anti-tumor necrosis factor alpha (anti-TNFalpha) 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-TNFalpha 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 < or = 5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for > or = 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-TNFalpha therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of MTX.


CONCLUSIONS
In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFalpha therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.
Schneeweiss
Sebastian
S
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA. schneeweiss@post.harvard.edu
Setoguchi
Soko
S
Weinblatt
Michael E
ME
Katz
Jeffrey N
JN
Avorn
Jerry
J
Sax
Paul E
PE
Levin
Raisa
R
Solomon
Daniel H
DH
D000068879:Adalimumab; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000382:microbiology* / Q000503:physiopathology; D001424:Bacterial Infections / Q000139:chemically induced* / Q000503:physiopathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D011203:Poverty; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate