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Gut 55:1131-1137 doi:10.1136/gut.2005.079392
  • Inflammatory bowel disease

Fontolizumab, a humanised anti-interferon γ antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn’s disease

  1. D W Hommes1,
  2. T L Mikhajlova2,
  3. S Stoinov3,
  4. D Štimac4,
  5. B Vucelic5,
  6. J Lonovics6,
  7. M Zákuciová7,
  8. G D’Haens8,
  9. G Van Assche9,
  10. S Ba10,
  11. S Lee10,
  12. T Pearce10
  1. 1Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands
  2. 2State Research Centre of Coloproctology, MZ RF, Department of Gastroenterology, Moscow, Russia
  3. 3MBAL Tsaritsa Ioanna, Department of Gastroenterology 8, Sofia, Bulgaria
  4. 4Division of Gastroenterology, Department of Internal Medicine, Clinical Hospital Centre Rijeka, Croatia
  5. 5Division of Gastroenterology, Department of Internal Medicine, University Hospital Rebro, Zagreb, Croatia
  6. 61st Department of Internal Medicine, Szentgyörgyi Albert Medical University, Szeged, Hungary
  7. 7I Internal Klinik, FNSP Tr SNP 1 Košice, Slovak Republic
  8. 8Gastroenterology, Imeldaziekenhuis, Bonheiden, Belgium
  9. 9Universitaire Ziekenhuizen Gasthuisberg, Division of Gastroenterology, Leuven, Belgium
  10. 10Protein Design Labs, Inc., Fremont, California, USA
  1. Correspondence to:
    Dr D W Hommes
    Department Gastroenterology and Hepatology, Academic Medical Centre, C2-111, Meibergdreef 9 1105 AZ, Amsterdam, the Netherlands; d.w.hommes{at}amc.uva.nl
  • Accepted 24 December 2005
  • Revised 22 December 2005
  • Published Online First 28 February 2006

Abstract

Introduction: Interferon γ is a potent proinflammatory cytokine implicated in the inflammation of Crohn’s disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon γ antibody, in patients with moderate to severe CD.

Methods: A total of 133 patients with Crohn’s disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI ⩽150).

Results: There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated.

Conclusion: Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.

Footnotes

  • Published online first 28 February 2006