Abstract

Background: Several clinical and experimental lines of evidence suggest that leukotriene 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-center, randomized, double-blind, placebo-controlled trial of patients with active RA of three month duration. A total of 342 patients were randomized to receive 5 mg, 25 mg, or 75 mg of BIIL 284 or placebo. The primary endpoint was the percentage of patients achieving an 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 to placebo, no statistically significant differences were observed between any of the three active treatment groups compared to placebo with regard to the primary or secondary endpoints. All trial treatments were safe and well tolerated.

Conclusions:This clinical trial demonstrated 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.