DefinitionThis section has been translated automatically.
Pharmacodynamics (Effect)This section has been translated automatically.
There are 2 randomized, double-blind, placebo-controlled, double-blind studies (GEMINI II and III) on the efficacy and safety of vedolizumab in adult patients with moderate to severe active Crohn's disease (Crohn's Disease Activity Index [CDAI] score of 220 to 450). In the GEMINI II study, 368 patients were examined in whom at least one of the following therapies was unsuccessful or was not tolerated: steroids, azathioprine/mercaptopurine, TNFalpha antagonists. Primary endpoints were the proportion of patients in clinical remission (defined as CDAI score ≤ 150 points) at week 6 and the proportion of patients with improved clinical response (defined as a decrease in CDAI score by ≥ 100 points from baseline) at week 6.
The results of these studies show that vedolizumab is an effective treatment for many patients with Crohn's disease. In the studies, vedolizumab not only improved the symptoms and thus the quality of life of the treated patients, but in many cases also led to a healing of the visible inflammation of the intestinal mucosa.
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Spectrum of actionThis section has been translated automatically.
Vedolizumab is a humanized monoclonal antibody that acts selectively in the gastrointestinal tract. It binds specifically to alpha4-beta7 integrin, which is preferentially expressed by T-helper lymphocytes located in the intestinal wall. By binding to alpha4- beta7 integrin, vedolizumab inhibits Th lymphocyte adhesion to MAdCAM-1 (mucosal addressin cellular adhesion molecule-1). MAdCAM-1 plays a critical role in the migration of T lymphocytes to tissues in the gastrointestinal tract and is mainly expressed by intestinal endothelial cells.
Vedolizumab does not bind to α4β1- and αEβ7-integrins and does not inhibit their function. The α4β7 integrin is expressed on a specific subset of memory T lymphocytes that preferentially migrate to the gastrointestinal (GI) tract and cause inflammation characteristic of ulcerative colitis (K51.9) and Crohn's disease (K50.9), both of which are chronic inflammatory immunologic-related diseases of the gastrointestinal tract. Vedolizumab reduces inflammation in the gastrointestinal tract in patients with ulcerative colitis. Inhibition of the interaction of α4β7 with MAdCAM-1 by vedolizumab prevents the migration of memory T lymphocytes migrating into the intestine through the vascular endothelium into the parenchymal tissue.
IndicationThis section has been translated automatically.
Vedolizumab is used to treat adult patients with moderate to severe active forms of ulcerative colitis or Crohn's disease in adults who have had an inadequate response or no longer respond to conventional immunosuppressants (e.g. azathioprine and corticosteroids) or anti-TNF treatment (e.g. infliximab or adalimumab) or who are intolerant to these drugs.
Dosage and method of useThis section has been translated automatically.
Ulcerative colitis: The recommended dose of 300 mg of vedolizumab is administered as an intravenous infusion to initiate treatment, after two and six weeks and then every eight weeks. Some patients in whom the response is slower may benefit from increasing the dosage frequency to 300 mg vedolizumab every four weeks.
Crohn's disease: The recommended dose of 300 mg of vedolizumab is given as an intravenous infusion to initiate treatment, after two and six weeks, and then every eight weeks; patients with Crohn's disease who have not responded may benefit from an increase in dosing frequency to 300 mg of vedolizumab every four weeks.
Elderly patients: Dose adjustment for elderly patients is not necessary. Population pharmacokinetic analyses showed no influence of age.
Children and adolescents: The safety and efficacy of vedolizumab in children aged 0 to 17 years is not proven. There are no data available.
Patients with kidney or liver dysfunction: Vedolizumab has not been studied in this group of patients. Dose recommendations cannot be given.
Route of administration: Entyvio® is intended for intravenous use only.
Undesirable effectsThis section has been translated automatically.
Very common (≥ 1/10): nasopharyngitis, headache, arthralgia.
Frequent (≥ 1/100, < 1/10): bronchitis, gastroenteritis, flu, sinusitis, pharyngitis, hypertension, cough, anal abscesses, anal fissures, nausea, constipation, flatulence, hemorrhoids, itching, eczema, erythema, night sweats, acne, muscle cramps, back pain, fatigue, fever.
Occasionally (≥ 1/1000 < 1/100): respiratory tract infection, vulvovaginal candidiasis, oral thrush, folliculitis, pain and irritation at the infusion site, infusion-related reactions, chills, sensation of cold.
PreparationsThis section has been translated automatically.
Entyvio® (Takeda GmbH)
LiteratureThis section has been translated automatically.
- Garnock-Jones KP (2015) Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. BioDrugs 29:57-67.