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Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis
  1. Federico Díaz-González1,
  2. Rieke H E Alten2,
  3. William G Bensen3,
  4. Jacques P Brown4,
  5. John T Sibley5,
  6. Maxime Dougados6,
  7. Stefano Bombardieri7,
  8. Patrick Durez8,
  9. Pablo Ortiz9,
  10. Gonzalo de-Miquel9,
  11. Alexander Staab10,
  12. Ralf Sigmund11,
  13. Laurence Salin12,
  14. Caroline Leledy12,
  15. Stephen H Polmar13,
  16. on behalf of the BIIL 284 Rheumatoid Arthritis Collaborative Study group*
  1. 1Service of Rheumatology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Canary Islands, Spain
  2. 2Schloβparkklinik, Berlin, Germany
  3. 3Charlton Medical Centre, Hamilton, Ontario, Canada
  4. 4Centre de l’osteoporose et de rheumatologie de Québec, Québec City, Québec, Canada
  5. 5Royal University Hospital, Saskatoon, Saskatchuan, Canada
  6. 6Unité de Rhumatologie, Hôpital Cochin de Paris, Paris, France
  7. 7Policlinico Santa Chiara UO Reumatologia, Pisa, Italy
  8. 8Cliniques Universitaires St-Luc, Brussells, Belgium
  9. 9Medical Department, Boehringer Ingelheim, Barcelona, Spain
  10. 10Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim, Biberach, Germany
  11. 11Medical Data Services, Boehringer Ingelheim, Biberach, Germany
  12. 12Medical Department, Boehringer Ingelheim, Reims, France
  13. 13Therapeutic Area Immunology, Boehringer Ingelheim, Ridgefield, Connecticut, USA
  1. 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}


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.

  • 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

Statistics from


  • * BIIL 284 Rheumatoid Arthritis Collaborative Study Group: Germany: Steffgen J; Fahmy Z; Schmidt R; Kellner H; Schönball Th; Müller-Ladner U; Herbert L; Neeck G; Kalden JR; Hammer M; Blaschke S; Demary W. Canada: Hart LJ; McKendry R; Kragg G; Haraomi B; Bell M; Homik J; Pope J; Atkins Ch; Thomson G; Bookman A. France: Lleu J-P; Combe B; Flipo RM; Auvinet B; Euller-Ziegler Ll; Goupille Ph; Cantagrel A; Sibilia J; Le Loet X; Thomas Ph; Kahan A. Spain: Camara J; Diaz Lopez C; Gonzalez MJ; Collantes E; Alegre C; Garcia de Vicuña R; Lerma JJ. Italy: Clementi L; Cutolo M; Gerli R; Montecucco C; Fantini F; Marcolongo R; Grassi W. Belgium: Oth Ch; Geusens P; Golstein M; Bentin J.

  • Published Online First 14 December 2006

  • Funding: This trial was supported by Boehringer Ingelheim.

  • Competing interests: None declared.

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