Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis.
BACKGROUND
Several clinical and experimental lines of evidence suggest that leucotriene B4 (LTB4), an arachidonic acid derivative with potent proinflammatory properties, plays a key role in the pathophysiology of rheumatoid arthritis (RA).


OBJECTIVE
To evaluate the efficacy and safety of BIIL 284, an oral long-acting LTB4 receptor antagonist, as monotherapy for the treatment of patients with active RA.


METHODS
This was a multi-centre, randomised, double-blind, placebo-controlled trial of patients with active RA of 3 months' duration. A total of 342 patients were randomised to receive 5 mg, 25 mg or 75 mg of BIIL 284 or placebo. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR) 20.


RESULTS
Although a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg and 75 mg of BIIL 284 compared with those treated with placebo, no statistically significant differences were found between any of the three active treatment groups compared with the placebo group with regard to the primary or secondary end points. All trial treatments were safe and well tolerated.


CONCLUSIONS
This clinical trial demonstrates that treatment of patients with active RA with a potent oral long-acting LTB4 receptor antagonist produced only modest improvements in disease activity. The results of this trial support the conclusion that LTB4 is not a major contributor to the inflammatory process in RA.
Díaz-González
Federico
F
Service of Rheumatology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Canary Islands, Spain.
Alten
Rieke H E
RH
Bensen
William G
WG
Brown
Jacques P
JP
Sibley
John T
JT
Dougados
Maxime
M
Bombardieri
Stefano
S
Durez
Patrick
P
Ortiz
Pablo
P
de-Miquel
Gonzalo
G
Staab
Alexander
A
Sigmund
Ralf
R
Salin
Laurence
L
Leledy
Caroline
C
Polmar
Stephen H
SH
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000578:Amidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000578:Amidines; D002219:Carbamates; D018102:Receptors, Leukotriene B4; C424425:amelubant