A placebo-controlled, randomized, double-blinded study evaluating the safety of etanercept in patients with rheumatoid arthritis and concomitant comorbid diseases.
OBJECTIVE
To evaluate the safety of etanercept in patients with rheumatoid arthritis (RA) and concomitant comorbidities.


METHODS
The safety of etanercept (25 mg twice weekly) in RA patients with at least one comorbidity (i.e. diabetes mellitus, chronic pulmonary disease, recent pneumonia, recurrent infections) was evaluated in a 16-week placebo-controlled, randomized, double-blinded study. The primary endpoint was the incidence of medically important infections (MIIs; defined as those resulting in hospitalization or treatment with intravenous antibiotics).


RESULTS
Data from 535 patients were analysed; the study was terminated early because of slow enrolment and lower than predicted incidence of infections. Serious adverse events (5.9% placebo, 8.6% etanercept) were most commonly observed in the cardiovascular system. Six patients (1 placebo; 5 etanercept) died during the study; four deaths were attributed to cardiovascular events. The numerically higher mortality in the etanercept group was not statistically significant [relative risk (95% CI) = 5.06 (0.59, 42.99)] but remains unexplained. No etanercept-related increase in the incidence of MIIs (3.7% placebo, 3.0% etanercept) or overall infections was observed in the total study population or in subgroups of patients who were > or = 65 yrs of age, had diabetes or had chronic pulmonary disease.


CONCLUSIONS
Etanercept was generally well tolerated by RA patients with comorbidities. Serious adverse events and deaths occurred more frequently in the etanercept group but event numbers were small and CIs were broad, preventing reliable conclusions from being drawn. Although the study had limited statistical power, the incidence of MIIs in these patients was not increased by etanercept treatment.
Weisman
Michael H
MH
Division of Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. michael.weisman@cshs.org
Paulus
Harold E
HE
Burch
Francis X
FX
Kivitz
Alan J
AJ
Fierer
Joshua
J
Dunn
Meleana
M
Kerr
David R
DR
Tsuji
Wayne
W
Baumgartner
Scott W
SW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy*; D001249:Asthma / Q000150:complications / Q000188:drug therapy; D001424:Bacterial Infections / Q000150:complications*; D001991:Bronchitis / Q000150:complications / Q000188:drug therapy; D048909:Diabetes Complications / Q000188:drug therapy; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D018570:Risk Assessment; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014552:Urinary Tract Infections / Q000150:complications / Q000188:drug therapy
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept