Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein.
BACKGROUND
Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. This study evaluated the safety and efficacy of a novel TNF antagonist - a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (TNFR:Fc).


METHODS
In this multicenter, double-blind trial, we randomly assigned 180 patients with refractory rheumatoid arthritis to receive subcutaneous injections of placebo or one of three doses of TNFR:Fc (0.25, 2, or 16 mg per square meter of body-surface area) twice weekly for three months. The clinical response was measured by changes in composite symptoms of arthritis defined according to American College of Rheumatology criteria.


RESULTS
Treatment with TNFR:Fc led to significant reductions in disease activity, and the therapeutic effects of TNFR:Fc were dose-related. At three months, 75 percent of the patients in the group assigned to 16 mg of TNFR:Fc per square meter had improvement of 20 percent or more in symptoms, as compared with 14 percent in the placebo group (P<0.001). In the group assigned to 16 mg per square meter, the mean percent reduction in the number of tender or swollen joints at three months was 61 percent, as compared with 25 percent in the placebo group (P<0.001). The most common adverse events were mild injection-site reactions and mild upper respiratory tract symptoms. There were no dose-limiting toxic effects, and no antibodies to TNFR:Fc were detected in serum samples.


CONCLUSIONS
In this three-month trial TNFR:Fc was safe, well tolerated, and associated with improvement in the inflammatory symptoms of rheumatoid arthritis.
Moreland
L W
LW
University of Alabama at Birmingham, 35294-7201, USA.
Baumgartner
S W
SW
Schiff
M H
MH
Tindall
E A
EA
Fleischmann
R M
RM
Weaver
A L
AL
Ettlinger
R E
RE
Cohen
S
S
Koopman
W J
WJ
Mohler
K
K
Widmer
M B
MB
Blosch
C M
CM
D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome
D000906:Antibodies; D015703:Antigens, CD; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins