Vedolizumab

Vedolizumab
Mass / length primary structure	146.8 kDa
Identifier
External IDs	CAS number : 943609-66-3
Drug information
ATC code	L04 AA33
Drug class	Immunosuppressant , monoclonal antibody

Vedolizumab (trade name Entyvio ^® , a product of Takeda ) is a humanized monoclonal antibody selected from the group of integrin - antagonists . It is used to treat adults with ulcerative colitis or Crohn's disease . Vedolizumab is used to treat moderate to severe illnesses in which conventional therapy or TNF-α antagonists have been shown to be ineffective, no longer effective, or cannot be tolerated by the patient.

Clinical information

Application areas (indications)

• Ulcerative Colitis - Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have either had an inadequate response to conventional therapy or one of the tumor necrosis factor alpha (TNFα) antagonists, who no longer respond or who are intolerant to a corresponding one Exhibit treatment.
• Crohn's Disease - Vedolizumab is indicated for the treatment of adult patients with moderately to severely active Crohn's Disease who have either had an inadequate response or an intolerance to conventional therapy or one of the tumor necrosis factor alpha (TNFα) antagonists Exhibit treatment.

Type and duration of application

Vedolizumab is given as an intravenous infusion over 30 minutes. Patients should be monitored during and after the infusion.

The patient is given 300 mg of vedolizumab per infusion. After the first infusion, another infusion is given after two and six weeks. The following infusions of vedolizumab are then carried out every eight weeks.

Contraindications (contraindications)

Vedolizumab must not be used in patients who are hypersensitive to the active substance itself. There is a contraindication in the presence of severe infections (e.g. tuberculosis , sepsis , diseases caused by the cytomegalovirus or listeriosis ).

Drug interactions

Live vaccines (administered by swallowing) should be used with caution .

Use during pregnancy and breastfeeding

Due to the (lack of) available data, vedolizumab may only be used during pregnancy if a strict benefit-risk assessment is positive. Women of childbearing potential should use safe contraception for at least 18 weeks after the last dose of vedolizumab. Animal studies show that vedolizumab is not teratogenic but is excreted in milk.

Adverse effects (side effects)

The following adverse events were observed with vedolizumab in clinical trials:

• very common: headache, joint pain and colds
• Common : bronchitis , gastrointestinal inflammation , upper respiratory tract infections, flu, sinusitis , colds, paresthesias , high blood pressure , nasal congestion , cough, pain in the mouth and throat, anal abscesses and fissures, nausea, indigestion, constipation, flatulence, Hemorrhoids , rash, itching, eczema , reddening of the skin , night sweats, acne, muscle cramps, back pain, muscle weakness, fatigue and fever
• uncommon: oral thrush , vulvovaginal candidiasis, folliculitis , irritation at the infusion site, infusion-related reactions with mild and moderate course, chills and feeling cold

Pharmacological information

Mechanism of action

The highly selective blockade of α ₄ β ₇ - integrin (adhesion molecule on the surface of activated lymphocytes ) is prevented that these bind to the MAdCAM associated receptors (docking sites). Without this docking, the activated lymphocytes cannot migrate into the tissue and further inflammation is suppressed. According to the manufacturer, the effect of vedolizumab is gut-specific, as the MAdCAM receptors are predominantly present in the gut. The immune cells are thus prevented from entering the intestinal tissue.

Unlike Natalizumab , an integrin inhibitor for multiple sclerosis has been developed and, in the US only in Crohn's disease is approved, which should through the intestinal specificity side effect of immunosuppression of the brain and in related reactivation of the JC virus with possibly fatal progressive multifocal leukenzelopathy (PML). At least no cases occurred in the GEMINI program; post-surveillance remains to be seen.

Vedolizumab has no effect on α ₄ β ₁ integrin, which binds to the vascular cell adhesion molecule 1 (VCAM-1). This does not affect the immune response mediated by VCAM-1 lymphocytes.

Absorption and distribution in the body (pharmacokinetics)

Vedolizumab does not cross the blood-brain barrier . It has a half-life of around 25 days.

Studies

In the GEMINI program, a total of three randomized, double-blind and placebo-controlled phase III studies with 2,426 patients from 40 countries were carried out. All three studies have already been published. In these, 895 patients with ulcerative colitis (GEMINI I) and 1,115 (GEMINI II) resp. 416 patients (GEMINI III) with Crohn's disease participated. At least one conventional therapy including glucocorticoids , immunomodulators and / or TNF blockers had failed in all patients . Patients with ulcerative colitis responded to 47% after 6 weeks (26% in the placebo arm). Patients with Crohn's disease responded 48% after 10 weeks (24% in the placebo arm). The side effects in patients with ulcerative colitis were comparable frequently in Vedolizumab arm as in the placebo arm.

Admission status

Vedolizumab has been approved in both the US and Europe for adults with moderately to severely active ulcerative colitis or moderately to severely active Crohn's disease , inadequate or absent response to conventional therapy or TNF-α antagonists, or corresponding intolerance. In the USA, the drug received "Priority Review Status", which means an accelerated approval process. The benefits of the drug are at least significant so far. To date, no progressive multifocal leukoencephalopathy (PML ) or other catastrophic complications have been observed. In December 2013 Takeda received the recommendation of the FDA Advisory Committee for approval in the USA or In March 2014 the CHMP voted in favor of European approval.

Additional benefit compared to anti-TNF-α therapies

On the basis of the existing data, the Institute for Quality and Efficiency in Health Care (IQWiG) in October 2014 and the Federal Joint Committee (G-BA) in January 2015 were unable to certify any additional benefit of vedolizumab compared to anti-TNF-α therapy. In a statement from the manufacturer Takeda it says u. a .: The assessment of no additional benefit means that vedolizumab is classified as at least as good as comparable therapies. This assessment by IQWiG does not mean that vedolizumab is of no use for patients with ulcerative colitis or Crohn's disease. The effectiveness has already been confirmed by the approval.

literature

• Doris Uhl: Dispute about the additional benefit of vedolizumab Deutsche Apotheker-Zeitung , October 16, 2014
• Monika Neubeck: Vedolizumab In: Neue Arzneimittel, Supplement to the Deutsche Apotheker-Zeitung, No. 10, Volume 61, October 2014, pages 70–72

Individual evidence

1. ↑ ^{a b} FDA approves Entyvio to treat ulcerative colitis and Crohn's disease , PM of the Food and Drug Administration (FDA) of May 20, 2014, accessed October 8, 2014.
2. ↑ ^{a b} European public assessment report (EPAR) for Entyvio , EPAR of the European Medicines Agency (EMA) , English, accessed on October 8, 2014.
3. ↑ ^{a b} Summary of the EPAR for the public , EPAR in German, accessed on October 8, 2014.
4. ↑ ^{a b c} Entyvio Fachinformation , Rote Liste, Fachinfo-Service, accessed on October 21, 2014.
5. ↑ ^{a b} Brian G. Feagan, Paul Rutgeerts, Bruce E. Sands, Stephen Hanauer, Jean-Frederic Colombel, William J. Sandborn, Gert Van Assche, Jeffrey Axler, Hyo-Jong Kim, Silvio Danese, Irving Fox, Catherine milk, Serap Sankoh, Tim Wyant, Jing Xu, Asit Parikh: Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis. In: New England Journal of Medicine . 369, 2013, pp. 699-710, doi : 10.1056 / NEJMoa1215734 .
6. ↑ William J. Sandborn, Brian G. Feagan, Paul Rutgeerts, Stephen Hanauer, Jean-Frederic Colombel, Bruce E. Sands, Milan Lukas, Richard N. Fedorak, Scott Lee, Brian Bressler, Irving Fox, Maria Rosario, Serap Sankoh, Jing Xu, Kristin Stephens, Catherine Milch, Asit Parikh: Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease. In: New England Journal of Medicine. 369, 2013, pp. 711-721, doi : 10.1056 / NEJMoa1215739 .
7. ↑ ^{a b} B. Sands, B. Feagan, P. Rutgeerts, J.-F. Colombel, W. Sandborn, R. Sy, G. D'Haens, S. Ben-Horin, J. Xu, I. Fox, A. Parikh, C. Milch, S. Hanauer: Vedolizumab induction therapy for patients with Crohn's disease and prior anti-tumor necrosis factor antagonist failure: a randomized, placebo-controlled, double-blind, multicenter trial. In: Journal of Crohn's and Colitis Volume 7, Supplement 1, Pages S5-S6, February 2013, doi : 10.1016 / S1873-9946 (13) 60012-4 .
8. ^ Takeda Pharmaceutical Company on vedolizumab , Takeda press release dated August 22, 2013, accessed April 3, 2014.
9. ↑ Takeda's New Investigational Drug Vedolizumab is Granted Priority Review Status by US Food and Drug Administration for Ulcerative Colitis , Takeda press release dated September 4, 2013, accessed March 25, 2014.
10. ↑ Studies show Vedolizumab is an effective treatment for Crohn's disease and ulcerative colitis .
11. ↑ FDA Advisory Committee Recommends Approval of Takeda's Investigational Biologic Vedolizumab , Takeda press release dated December 9, 2013, accessed March 25, 2014.
12. ↑ Takeda Receives Positive CHMP Opinion for Entyvio® (vedolizumab) in Europe for the Treatment of Ulcerative Colitis and Crohn's Disease , Takeda press release of March 24, 2014, accessed on March 25, 2014.
13. ↑ Added benefit of vedolizumab is not proven IQWiG press release of October 15, 2014.
14. ↑ Patients can benefit from vedolizumab - IQWiG does not recognize any added benefit from PM from Takeda from October 16, 2014.

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