EXTENDED REPORT

¹ Service of Rheumatology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Canary Islands, Spain
² Schloßparkklinik, Berlin, Germany
³ Charlton Medical Centre, Hamilton, Ontario, Canada
⁴ Centre de l’osteoporose et de rheumatologie de Québec, Québec City, Québec, Canada
⁵ Royal University Hospital, Saskatoon, Saskatchuan, Canada
⁶ Unité de Rhumatologie, Hôpital Cochin de Paris, Paris, France
⁷ Policlinico Santa Chiara UO Reumatologia, Pisa, Italy
⁸ Cliniques Universitaires St-Luc, Brussells, Belgium
⁹ Medical Department, Boehringer Ingelheim, Barcelona, Spain
¹⁰ Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim, Biberach, Germany
¹¹ Medical Data Services, Boehringer Ingelheim, Biberach, Germany
¹² Medical Department, Boehringer Ingelheim, Reims, France
¹³ Therapeutic Area Immunology, Boehringer Ingelheim, Ridgefield, Connecticut, USA

Correspondence to:
Dr S H Polmar
Therapeutic Area Immunology, Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA; spolmar{at}rdg.boehringer-ingelheim.com

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.

Abbreviations: ACR, American College of Rheumatology; AE, adverse event; CIA, collagen-induced arthritis; DMARD, disease-modifying anti-rheumatic drug; 5-LO, 5-lipoxygenase; LTB4, leucotriene B4; RA, rheumatoid arthritis; VAS, visual analogue scale

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