A randomized placebo-controlled trial of pegylated interferon alpha in active ulcerative colitis

Tilg, Herbert; Vogelsang, H.; Ludwiczek, Othmar; Lochs, H.; Kaser, Arthur; Jf, Colombel; Ulmer, Hanno; Rutgeerts, Paul; Krüger, Sandra; Cortot, Antoine; D’Haens, G; Harrer, M.; Gasché, Ch.; Wrba, Fritz; Kühn, Ingrid; Reinisch, Walter

doi:10.1016/s0016-5085(03)80305-0

Cited by 32 publications

(4 citation statements)

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“…The largest randomized controlled trial of pegylated IFN-a in 60 patients with active UC however failed to show clinical efficacy, although the higher dose of 1 mg/kg subcutaneously showed biological efficacy with a significant decrease in C reactive protein (CRP) concentrations. 11 Overall, the evidence for the efficacy of type I interferons in IBD is therefore unconvincing.…”

mentioning

confidence: 99%

Interfering with interferons in inflammatory bowel disease

Ghosh

Chaudhary²,

Carpani³

et al. 2005

Gut

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confidence: 99%

Interfering with interferons in inflammatory bowel disease

Ghosh

Chaudhary²,

Carpani³

et al. 2005

Gut

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“…In two uncontrolled trials on patients with left-sided UC, IFN 2a obtained a remission rate of 82% that was equivalent to corticosteroids enemas [117,118]. The pegylated-IFN -2b, in a placebo-controlled trial on 60 UC patients, obtained at 0.5 g/Kg dose a response rate only of 18% better than placebo, with the counterpart of very frequent side effects [119]. Even if preliminary data on IFN--1 suggested efficacy [120] in steroid-dependent UC patients, two successive placebo-controlled studies have not confirmed the results [121,122].…”

Section: Immunomodulatorsmentioning

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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“…In a study performed in 32 patients with mild-moderate left colitis, interferon α2a proved as effective as steroid enemas (110). A study with pegylated interferon α2b showed that this drug was poorly tolerated by patients (111).…”

Section: Immunomodulatorsmentioning

confidence: 99%

Biologic therapies for chronic inflammatory bowel disease

Martínez-Montiel

Muñoz-Yagüe

2006

Rev. esp. enferm. dig.

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Crohn's disease (CD) and ulcerative colitis (UC) make up the so-called chronic inflammatory bowel disease (IBD). Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Antiintegrin α4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors.Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab), T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.Key words: Inflammatory bowel disease. Crohn's disease. Ulcerative colitis. Therapy. 2006; 98: 265-291. Martínez-Montiel MP, Muñoz-Yagüe MT. Biologic therapies for chronic inflammatory bowel disease. Rev Esp Enferm Dig INTRODUCTIONCrohn's disease (CD) and ulcerative colitis (UC) make up the so-called inflammatory bowel disease (IBD). Advances in the knowledge of this condition's etiopathogenesis have been correlated to the development of novel therapeutic agents. Medical treatment is currently the cornerstone for managing these conditions, and surgery is reserved for complications or treatment refractoriness (1). The available therapeutic armamentarium includes anti-inflammatory drugs (aminosalicylates and steroids), antibiotics, and immune modulators (azathioprine, 6-mercaptopurin, cyclosporin and methotrexate). All these drugs result in a nonspecific suppression of inflammatory processes, and their use during the past few years has determined a relevant advance in BDI control. However, their efficacy is limited and they are not exempt from side effects. Biologic therapies, at least theoretically, would be more therapeutically effective with fewer side effects, and thus would represent more specific means for t...

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A randomized placebo-controlled trial of pegylated interferon alpha in active ulcerative colitis

Cited by 32 publications

References 23 publications

Interfering with interferons in inflammatory bowel disease

Interfering with interferons in inflammatory bowel disease

Biological Therapies For Inflammatory Bowel Disease: Research DrivesClinics

Biologic therapies for chronic inflammatory bowel disease

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