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4 augustus 2014: onderaan het ik het abstract toegevoegd van deze studie waarvan het volledige studierapport gratis is in te zien: Is there a role for vedolizumab in the treatment of ulcerative colitis and Crohn’s disease? met interessante referentielijst. Ook deze studie is mooi voorbeeld van een medicine dat ingrijpt op basis van bepaalde DNA mutaties en receptorenexpressie. Onder de grafiek staat meer informatie over vedolizumab bij ziekte van Crohn

beeld vedolizumab

22 augustus 2013: Bron: NEJM

Vedoluzimab bljikt uitstekend te werken als preventie en behandeling van ontstekingen in de darmen, ziekte van Crohn en bij colitis ulcerosa. Dit blijkt uit twee grote vergelijkende placebo gecontroleerde studies bij totaal ruim 2000 patiënten uitgevoerd in 39 landen. De verschillen waren statistisch significant.

Studieresultaten:

De onderzoekers hebben twee gerandomiseerde, dubbelblinde, placebo gecontroleerde studies van vedolizumab bij patiënten met een actieve ziekte met elkaar vergeleken. Als aanvangsbehandeling ontvingen 374 patiënten (cohort 1) vedolizumab (een dosis van 300 mg) of intraveneus een placebo in de weken 0 en 2.  521 patiënten (cohort 2) kregen een open-label vedolizumab in de weken 0 en 2. In week 6 werden de resultaten geevalueerd. 

Als onderhoudsbehandeling kregen alle patiënten die goed hadden gereageerd op vedolizumab vervolgens willekeurig ingedeeld vedolizumab elke 8 of 4 weken of schakelden over op placebo gedurende 52 weken. Een respons werd gedefinieerd als een vermindering van de scores zoals die zijn vastgelegd in de Mayo Clinic (range, 0 tot 12, met hogere scores die meer actieve ziekte betekenen) van ten minste 3 punten en een daling van ten minste 30% van de uitgangswaarde, met een begeleidende afname in de rectale bloedingen subscore van minimaal 1 punt of een absolute rectale bloedingen subscore van 0 of 1.

Resultaten
Respons in week 6 was 47,1% onder patiënten in de vedolizumab groep en en 25,5% bij de patiënten uit de placebogroep (verschil met aanpassing voor stratificatiefactoren, 21,7 procentpunten; 95% betrouwbaarheidsinterval [BI], 11,6-31,7; P <0.001) . Na 1 jaar in week 52 bleken 41.8% van de patiënten die vedolizumab bleven ontvangen elke 8 weken en 44,8% van de patiënten die vedolizumab bleven ontvangen elke 4 weken in klinische remissie (Mayo Clinic score ≤ 2 en geen subscore> 1), vergeleken met 15,9 % van de patiënten die overschakelden naar placebo (gecorrigeerde verschil, 26,1 procentpunten voor vedolizumab elke 8 weken versus placebo ingeschakeld [95% BI, 14,9-37,2; P <0.001] en 29,1 procentpunten voor vedolizumab elke 4 weken versus placebo [95% BI, 17,9-40,4; P <0.001]). De frequentie van bijwerkingen was vergelijkbaar in de vedolizumab groep en de placebo groep.

Het volledige studieverslag: Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis is in te zien in de NEJM. Hier het abstract van deze studie

Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis

Original Article

Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis

Brian G. Feagan, M.D., Paul Rutgeerts, M.D., Ph.D., Bruce E. Sands, M.D., Stephen Hanauer, M.D., Jean-Frédéric Colombel, M.D., William J. Sandborn, M.D., Gert Van Assche, M.D., Ph.D., Jeffrey Axler, M.D., Hyo-Jong Kim, M.D., Ph.D., Silvio Danese, M.D., Ph.D., Irving Fox, M.D., Catherine Milch, M.D., Serap Sankoh, Ph.D., Tim Wyant, Ph.D., Jing Xu, Ph.D., and Asit Parikh, M.D., Ph.D. for the GEMINI 1 Study Group

N Engl J Med 2013; 369:699-710 August 22, 2013 DOI: 10.1056/NEJMoa1215734

Background

Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.

Methods

We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.

Results

Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval , 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.

Conclusions

Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.)

Is there a role for vedolizumab in the treatment of ulcerative colitis and Crohn’s disease?

Clin Exp Gastroenterol. 2014; 7: 163–172.
Published online May 22, 2014. doi:  10.2147/CEG.S45261
PMCID: PMC4038524

Is there a role for vedolizumab in the treatment of ulcerative colitis and Crohn’s disease?

Leah Gilroy and Patrick B Allen
Author information ► Copyright and License information ►
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Abstract

Inflammatory bowel disease (IBD) is an important cause of morbidity and mortality for millions of patients worldwide. Current treatment options include corticosteroids, 5-aminosalicylates, immunosuppressants, and TNFα antagonists. However, these are frequently ineffective in achieving sustained response and remission over time. At present, gastroenterologists lack safe and effective treatments if patients fail anti-TNF therapy. Vedolizumab is a promising new agent for IBD patients refractory to anti-TNF therapy. Vedolizumab is an integrin antagonist which is thought to act by reducing inflammation by selectively inhibiting leukocyte migration in the gut. Emerging evidence from clinical trials suggests a potential role for vedolizumab in both ulcerative colitis (UC) and Crohn’s disease (CD), particularly in patients who have previously failed biological therapy. The safety profile of vedolizumab appears reasonable, possibly because it has a “gut-selective” mode of action, with no reported cases of progressive multifocal leukoencephalopathy, a condition which has been linked to another integrin antagonist, natalizumab. This review discusses the available evidence for integrin antagonists and their potential role in the management of IBD.

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voedingsuppletie, voeding, endeldarmkanker, poliepen, darmkanker, ziekte van Crohn, vedolizumab


Plaats een reactie ...

2 Reacties op "Vedolizumab voorkomt en geneest ontstekingen in darmen en lijkt uitstekend medicijn bij ziekte van Crohn"

  • garfield :
    21/06/2014
    Tot nu toe is de ziekte van Crohn nog niet te genezen. Er zijn heel veel onderhoudsmedicijnen die je kan innemen als je ontstekingen in je darm hebt. Voor elke patiënt is dit verschillend hoe ze hierop reageren. Ik heb vanaf 1980 de ziekte van Crohn en 4 keer geopereerd aan een vernauwing ( stenose). Ik heb al heel veel medicijnen uitgeprobeerd. Ik had heel veel last van de bijwerkingen van de medicijnen. Als er tijdens een colonoscopie weer ontstekingen geconstateerd worden, zal ik eens vragen aan mijn MDL-arts of dit nieuwe medicijn iets voor mij is.
    Ik wil het zeker een keer uitproberen. Tot nu toe reageer ik alleen goed op het medicijn entocort.
    Comment
  • arwind :
    11/11/2013
    kan de ziekte van croh en colitius genezen worden?
    Comment

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