Efficacy, Safety and Tolerability of Vidofludimus in Patients With Inflammatory Bowel Disease: The ENTRANCE Study

Herrlinger, Klaus; Diculescu, Mircea; Fellermann, Klaus; Hartmann, Heinz; Howaldt, Stefanie; Nikolov, Rossen; Petrov, Asen; Reindl, Wolfgang; Otte, Jan-Michel; Stoĭnov, S; Strauch, Ulrike; Sturm, Andreas; Voiosu, R; Ammendola, Aldo; Dietrich, Bruno; Hentsch, Bernd; Stange, Eduard F.

doi:10.1016/s0016-5085(11)62435-9

Cited by 22 publications

(26 citation statements)

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“…Though vidofludimus showed clinical efficacy and a good safety profile in this first IBD trial, further and more defined studies will be needed to obtain more meaningful data [72].…”

Section: Lebrikizumabmentioning

confidence: 91%

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

Scharl

Vavricka²,

Rogler

2013

CDT

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Significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). A number of susceptibility genes have been detected by large genome wide screening-approaches. New therapeutic concepts emerge from these insights. The most important progress in recent years certainly is the introduction of biologics in the therapy of IBD. TNF blockers have been shown to be very effective for the control of complicated disease courses. Currently, in addition to the three already established anti-TNF antibodies, new anti-TNF molecules, for example Golimumab, are in clinical trials and also reveal promising results. However, not all of the patients respond to anti-TNF treatment and many patients lose their response. Therefore, additional therapeutic approaches are urgently needed. Attractive therapy targets are cytokines as well as their receptors and signaling pathways. At the moment a large number of biologicals and inhibitors are tested in clinical trials and some of them provide very promising results for the treatment of IBD patients. In particular, inhibition of IL-12p40 by specific antibodies as well as of the janus kinase (JAK)3 by a small molecule promise to be very effective approaches. Though antibodies targeting for example IL-6, IL-6R, IL-13 or CCR9 are only in the early steps of clinical development, they have already demonstrated to be a possible treatment option which needs to be confirmed in further trials. Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed. Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed.

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“…Though vidofludimus showed clinical efficacy and a good safety profile in this first IBD trial, further and more defined studies will be needed to obtain more meaningful data [72].…”

Section: Lebrikizumabmentioning

confidence: 91%

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

Scharl

Vavricka²,

Rogler

2013

CDT

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“…In humans, suppression of IL-17A and IL-17F production can be obtained with vidofludimus (formerly SC12267 or 4SC-101), a small molecule that inhibits the enzyme dihydroorotate dehydrogenase, involved in the de novo biosynthesis of pyrimidine by converting dihydroorotate to orotate [76]. There is preliminary evidence that vidofludimus attenuates chemical-induced colitis in mice [76] and can induce remission in both CD and UC patients when administered orally [77]. In a small open label uncontrolled study, 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission after 12-week treatment [77].…”

Section: Inhibitors Of T Cell Differentiation or T Cell-derived Cytokmentioning

confidence: 99%

“…There is preliminary evidence that vidofludimus attenuates chemical-induced colitis in mice [76] and can induce remission in both CD and UC patients when administered orally [77]. In a small open label uncontrolled study, 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission after 12-week treatment [77].…”

Section: Inhibitors Of T Cell Differentiation or T Cell-derived Cytokmentioning

confidence: 99%

Targeting T cells in Chronic Inflammatory Bowel Diseases

Caprioli¹,

Marafini²,

Facciotti³

et al. 2013

J Clin Cell Immunol

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The pathological process that causes tissue damage in Crohn's disease (CD) and ulcerative colitis, the major inflammatory bowel diseases (IBD) in humans, is supposed to be mediated by distinct subsets of effector T cells, which accumulate in inflamed intestine of patients as a result of multiple mechanisms. These include enhanced recruitment of T cells from the systemic circulation, increased cell cycling and resistance against apoptotic stimuli. Within the inflamed gut, effector T cells produce elevated levels of cytokines, which target multiple immune and nonimmune cell types thus contributing to amplify the detrimental inflammatory response. Strategies aimed at blocking T cell function in the gut have been employed with some success in patients with CD and patients with UC.

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“…Some patients with moderate to severe CD are intolerant and/or nonresponsive to azathioprine/6-mercaptopurine and anti-tumor necrosis factor-␣ antibodies (Prajapati et al, 2003;Holtmann et al, 2008). Therefore, other immunomodulatory drugs [including vidofludimus (Vido)] have been investigated in clinical trials for the treatment of IBD (Prajapati et al, 2003;Holtmann et al, 2008;Herrlinger et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

Fitzpatrick

Small

Doblhofer

et al. 2012

J Pharmacol Exp Ther

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Vidofludimus (Vido) is a novel oral immunomodulatory drug that inhibits dihydro-orotate dehydrogenase and lymphocyte proliferation in vitro. Vido inhibits interleukin (IL)-17 secretion in vitro independently of effects on lymphocyte proliferation. Our primary goal was to evaluate the in vivo effects of Vido on IL-17 secretion and the parameters of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. To further delineate the mechanism of action for Vido, rats were dosed concomitantly with uridine (Uri). Young Wistar rats received a 150-l enema of either phosphate-buffered saline (PBS) or TNBS on study day 1. The ex vivo effects of Vido on 24-h colonic IL-17 secretion were determined by using colonic strips from PBS-or TNBStreated rats. Some rats were dosed with vehicle, Vido, or Vido ϩ Uri for 6 days. On day 6, the parameters of colitis were determined from colonic tissue. These parameters included macroscopic, histological, and transcription factor measurements, IL-17 production, and numbers of CD3 ϩ T cells. Ex vivo Vido completely blocked IL-23 ϩ IL-1␤-stimulated secretion of IL-17 by colonic strips. In vivo Vido treatment alone most effectively reduced macroscopic and histological pathology and the numbers of CD3 ϩ T cells. In contrast, similarly reduced nuclear signal transducer and activator of transcription 3 (STAT3) binding and IL-17 levels were observed from animals treated with Vido alone and Vido ϩ Uri. Vido improves TNBS-induced colonic inflammation by a unique dual mode of action: 1) inhibiting expansion of colonic T lymphocytes, and 2) suppressing colonic IL-17 production, which is independent from the control of T-lymphocyte proliferation, by inhibition of STAT3 and nuclear factor-B activation.

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Efficacy, Safety and Tolerability of Vidofludimus in Patients With Inflammatory Bowel Disease: The ENTRANCE Study

Cited by 22 publications

References 0 publications

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

Targeting T cells in Chronic Inflammatory Bowel Diseases

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

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