Fontolizumab (Huzaf), a humanized anti-IFN-gamma antibody, has clinical activity and excellent tolerability in moderate to severe Crohn’s disease

Hommes, Daniël W.; Mikhajlova, Tatiana; Stoĭnov, S; Štimac, Davor; Vucelić, Boris; Lonovics, János; Zakuciová, Mária; D’Haens, Geert R.; Assche, Gert Van; Pearce, Tillman

doi:10.1053/j.gastro.2004.05.011

Cited by 29 publications

(11 citation statements)

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“…A similar phenomenon has been reported in other placebo-controlled trials of a variety of other biologic agents in patients with Crohn's disease. [7][8][9] Subgroup analyses of these other studies have demonstrated that a lower concentration of C-reactive protein was associated with a higher likelihood of a response to placebo. Furthermore, a meta-analysis of factors contributing to higher rates of a response to placebo in induction trials involving patients with active Crohn's disease demonstrated that the duration of the study (greater than eight weeks), the frequency of study visits (less than four weeks apart), and the CDAI score at entry (less than 200 points) were important predictors of the rate of remission in the placebo group, with the duration of the study as the most important independent predictor.…”

Section: The New Englandmentioning

confidence: 99%

Natalizumab Induction and Maintenance Therapy for Crohn's Disease

et al. 2005

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Section: The New Englandmentioning

confidence: 99%

Natalizumab Induction and Maintenance Therapy for Crohn's Disease

et al. 2005

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“…A pilot randomized double blind placebo-controlled trial of a humanized anti-IL-6 receptor monoclonal antibody that included thirty-six patients were randomized biweekly to receive either a placebo, 8 mg/kg MRA or MRA/placebo alternately for 12 week. The clinical remission rate with biweekly MRA was significantly higher than with placebo (80% vs 31%) [35].…”

Section: Recombinant Cytokinesmentioning

confidence: 78%

Current and Future Biological Treatments in Inflammatory Bowel Disease

Yamamoto‐Furusho¹

2011

Gene Therapy Applications

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“…Preliminary results, coming from a small phase IIa study on 28 CD patients [78] and from a larger phase II study on 196 patients treated with increasing doses (up to 4 mg/Kg) of fontolizumab failed to demonstrate efficacy [79]. Later on, an high-dose phase II trial on 133 patients with active CD has been conducted [80]. Patients were randomized to receive 1 or 2 infusions (days 0 and 28) of fontolizumab at 4 or 10 mg/Kg dose.…”

Section: Anti-ifn-antibody (Fontolizumab)mentioning

confidence: 99%

Biological Therapies For Inflammatory Bowel Disease: Research DrivesClinics

Danese¹,

Semeraro²,

Armuzzi³

et al. 2006

MRMC

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The better understanding of the mechanisms of inflammatory bowel disease has driven our progress into the development of new biological therapies targeting specific molecules. Anti-TNF-alpha biologic compounds have shown great efficacy particularly in Crohn's disease. Infliximab (an IgG1 mouse/human chimeric monoclonal anti-TNF-alpha antibody fragment) is the most efficacious compound in induction and maintenance therapy of active and fistulizing Crohn's disease, being at present the only biological compound approved for therapy, but with the limit of the immunogenicity; CDP-571 (a humanized anti-TNF-alpha antibody) and CDP-870 (a PEGylated anti-TNF-alpha antibody) are less immunogenic, showed some efficacy in induction therapy in Crohn's disease but a rapid loss of response in maintenance therapy. Etanercept and onercept (soluble human recombinant TNF-alpha receptors fusion proteins) seem not to be efficacious in Crohn's disease demonstrating no class-effect for anti-TNF-alpha compounds. In preliminary study, adalimumab (an IgG1 humanized monoclonal anti-TNF-alpha antibody) offers good perspective of efficacy and safety also in infliximab-resistant or allergic patients. Inhibition of lymphocyte trafficking to the gut, through anti-adhesion molecules specific therapies (natalizumab, MLN-02, alicaforsen), has shown promising results: unfortunately, natalizumab, the most effective drug of this class, has recently been suspected to favour serious neurological complications. Other biologic therapies are under evaluation but at present seem to be less promising than infliximab; they consist of antiinflammatory cytokines, inhibitors of proinflammatory cytokines, hormones and growth factors: anti-IL12-antibody, interferon-alpha, interferon-beta, G-CSF, GM-CSF, EGF, growth hormone, anti-interferon-gamma, anti-IL-18, anti-IL-2-receptor and anti-CD3 antibodies. The evaluation of other biological drugs has been suspended for severe side effects as happened for anti-CD40L antibody causing thromboembolism and anti-CD4 antibody causing ly.mphopenia. Other compounds as IL-10 and IL-11 have been proven to be ineffective even if an oral formulation of IL-11 is under evaluation. Among the MAP kinases inhibitors BIRB-796 and RDP58 showed to be ineffective while CNI-1493 is under evaluation. The effort in identifying specific patients features predicting therapy response and the possible combination of different biological therapies represent undoubtedly a very promising perspective. Aim of this article is to review the biological compounds and their efficacy in IBD.

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Fontolizumab (Huzaf), a humanized anti-IFN-gamma antibody, has clinical activity and excellent tolerability in moderate to severe Crohn’s disease

Cited by 29 publications

References 0 publications

Natalizumab Induction and Maintenance Therapy for Crohn's Disease

Natalizumab Induction and Maintenance Therapy for Crohn's Disease

Current and Future Biological Treatments in Inflammatory Bowel Disease

Biological Therapies For Inflammatory Bowel Disease: Research DrivesClinics

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