Fontolizumab in moderate to severe Crohn's disease

A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study

Walter Reinisch, Williem De Villiers, L. Bene, László Simon, I. Rácz, Seymour Katz, I. Altorjay, Brian Feagan, Dennis Riff, Charles N. Bernstein, Daniel Hommes, Paul Rutgeerts, Antoine Cortot, Michael Gaspari, May Cheng, Tillman Pearce, Bruce E. Sands

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%-38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%-75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalInflammatory Bowel Diseases
Volume16
Issue number2
DOIs
Publication statusPublished - 2010

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Crohn Disease
Placebos
C-Reactive Protein
Interferon-gamma
fontolizumab
Neutralizing Antibodies
Cytokines
Safety
Antibodies

Keywords

  • Clinical study
  • Crohn's disease
  • Fontolizumab
  • Inflammatory bowel disease
  • Interferon gamma

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Fontolizumab in moderate to severe Crohn's disease : A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. / Reinisch, Walter; De Villiers, Williem; Bene, L.; Simon, László; Rácz, I.; Katz, Seymour; Altorjay, I.; Feagan, Brian; Riff, Dennis; Bernstein, Charles N.; Hommes, Daniel; Rutgeerts, Paul; Cortot, Antoine; Gaspari, Michael; Cheng, May; Pearce, Tillman; Sands, Bruce E.

In: Inflammatory Bowel Diseases, Vol. 16, No. 2, 2010, p. 233-242.

Research output: Contribution to journalArticle

Reinisch, W, De Villiers, W, Bene, L, Simon, L, Rácz, I, Katz, S, Altorjay, I, Feagan, B, Riff, D, Bernstein, CN, Hommes, D, Rutgeerts, P, Cortot, A, Gaspari, M, Cheng, M, Pearce, T & Sands, BE 2010, 'Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study', Inflammatory Bowel Diseases, vol. 16, no. 2, pp. 233-242. https://doi.org/10.1002/ibd.21038
Reinisch, Walter ; De Villiers, Williem ; Bene, L. ; Simon, László ; Rácz, I. ; Katz, Seymour ; Altorjay, I. ; Feagan, Brian ; Riff, Dennis ; Bernstein, Charles N. ; Hommes, Daniel ; Rutgeerts, Paul ; Cortot, Antoine ; Gaspari, Michael ; Cheng, May ; Pearce, Tillman ; Sands, Bruce E. / Fontolizumab in moderate to severe Crohn's disease : A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 2. pp. 233-242.
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abstract = "Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67{\%}) completed the study. Day 29 response rates were similar in all treatment groups (31{\%}-38{\%}). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58{\%}-75{\%}); most events were related to exacerbation of CD. There was a low frequency (5.2{\%}) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted.",
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AU - Bene, L.

AU - Simon, László

AU - Rácz, I.

AU - Katz, Seymour

AU - Altorjay, I.

AU - Feagan, Brian

AU - Riff, Dennis

AU - Bernstein, Charles N.

AU - Hommes, Daniel

AU - Rutgeerts, Paul

AU - Cortot, Antoine

AU - Gaspari, Michael

AU - Cheng, May

AU - Pearce, Tillman

AU - Sands, Bruce E.

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N2 - Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%-38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%-75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted.

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