Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor alpha antagonists.
OBJECTIVE
To evaluate the risk of serious bacterial infections associated with tumor necrosis factor alpha (TNFalpha) antagonists among rheumatoid arthritis (RA) patients.


METHODS
A retrospective cohort study of US RA patients enrolled in a large health care organization identified patients who received either TNFalpha antagonists or methotrexate (MTX). Administrative data were used to identify hospitalizations with possible bacterial infections; corresponding medical records were abstracted and reviewed by infectious disease specialists for evidence of definite infections. Proportional hazards models evaluated time-dependent infection risks associated with TNFalpha antagonists.


RESULTS
Hospital medical records with claims-identified suspected bacterial infections were abstracted (n=187) among RA patients who received TNFalpha antagonists (n=2,393; observation time 3,894 person-years) or MTX (n=2,933; 4,846 person-years). Over a median followup time of 17 months, the rate of hospitalization with a confirmed bacterial infection was 2.7% among the patients treated with TNFalpha antagonists compared with 2.0% among the patients treated with MTX only. The multivariable-adjusted hazard ratio (HR) of infection among the patients who received TNFalpha antagonists was 1.9 (95% confidence interval [95% CI] 1.3-2.8) compared with patients who received MTX only. The incidence of infections was highest within 6 months after initiating TNFalpha antagonist therapy (2.9 versus 1.4 infections per 100 person-years; multivariable-adjusted HR 4.2, 95% CI 2.0-8.8).


CONCLUSIONS
The multivariable-adjusted risk of hospitalization with a physician-confirmed definite bacterial infection was approximately 2-fold higher overall and 4-fold higher in the first 6 months among patients receiving TNFalpha antagonists versus those receiving MTX alone. RA patients were at increased risk of serious infections, irrespective of the method used to define an infectious outcome. Patients and physicians should vigilantly monitor for signs of infection when using TNFalpha antagonists, particularly shortly after treatment initiation.
Curtis
Jeffrey R
JR
University of Alabama at Birmingham, Center for Education and Research on Therapeutics, AL 35294, USA.
Patkar
Nivedita
N
Xie
Aiyuan
A
Martin
Carolyn
C
Allison
Jeroan J
JJ
Saag
Michael
M
Shatin
Deborah
D
Saag
Kenneth G
KG
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001424:Bacterial Infections / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006279:Health Maintenance Organizations; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000009:adverse effects; D000069285:Infliximab; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate