Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy.
OBJECTIVE
Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk.


METHODS
RA patients (n = 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments.


RESULTS
After adjustment for covariates, prednisone use increased the risk of pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5-2.0]), including a dose-related increase in risk (< or = 5 mg/day HR 1.4 [95% confidence interval 1.1-1.6], > 5-10 mg/day HR 2.1 [95% confidence interval 1.7-2.7], > 10 mg/day HR 2.3 [95% confidence interval 1.6-3.2]). Leflunomide also increased the risk (HR 1.2 [95% confidence interval 1.0-1.5]). HRs for etanercept (0.8 [95% confidence interval 0.6-110]) and sulfasalazine (0.7 [95% confidence interval 0.5-1.0]) did not reflect an increased risk of pneumonia. HRs for infliximab, adalimumab, and methotrexate were not significantly different from zero.


CONCLUSIONS
There is a dose-related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti-tumor necrosis factor therapy or methotrexate. These data call into question the belief that low-dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.
Wolfe
Frederick
F
National Data Bank for Rheumatic Diseases and University of Kansas School of Medicine, Wichita, Kansas 67214, USA. fwolfe@arthritis-research.org
Caplan
Liron
L
Michaud
Kaleb
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007555:Isoxazoles / Q000009:adverse effects; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D011014:Pneumonia / Q000453:epidemiology* / Q000209:etiology; D011241:Prednisone / Q000009:adverse effects; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D000077339:Leflunomide; D011241:Prednisone; D008727:Methotrexate