The information below is based on the summary of product characteristics approved by regulatory authorities. For full details from the SmPC, please click here https://www.medicines.org.uk/emc/product/5442/smpc
Additional related ECCO e-Learning resources can be found under IBD Curriculum Topic 6.1-6.11
Introduction and Mechanism of Action
Vedolizumab is a gut-selective immunosuppressive biologic. It is a humanised monoclonal antibody that binds specifically to the α4β7 integrin, which is preferentially expressed on gut homing T helper lymphocytes. By binding to α4β7 on certain lymphocytes, vedolizumab inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but not to vascular cell adhesion molecule-1 (VCAM-1). MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T lymphocytes to tissues within the gastrointestinal tract. Vedolizumab does not bind to, nor inhibit function of, the α4β1 and αEβ7 integrins.
Therapeutic indications
Ulcerative colitis
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.
Crohn's disease
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.
Pouchitis
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active chronic pouchitis, who have undergone proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis, and have had an inadequate response with or lost response to antibiotic therapy.
Dosing, administration
Ulcerative colitis
The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter.
Therapy for patients with ulcerative colitis should be discontinued if no evidence of therapeutic benefit is observed by week 10.
Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to intravenous vedolizumab 300 mg every 4 weeks.
In patients who have responded to treatment with vedolizumab, corticosteroids may be reduced and/or discontinued in accordance with standard of care.
Retreatment
If therapy is interrupted and there is a need to restart treatment with intravenous vedolizumab, dosing at every 4 weeks may be considered. The treatment interruption period in clinical trials extended up to 1 year. Efficacy was regained with no evident increase in adverse reactions or infusion-related reactions during retreatment with vedolizumab.
Crohn's disease
The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter.
Patients with Crohn's disease, who have not shown a response may benefit from a dose of intravenous vedolizumab at week 10 (see section 4.4). Therapy should be continued every 8 weeks from week 14 in responding patients. Therapy for patients with Crohn's disease should be discontinued if no evidence of therapeutic benefit is observed by week 14.
Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to intravenous vedolizumab 300 mg every 4 weeks.
In patients who have responded to treatment with vedolizumab, corticosteroids may be reduced and/or discontinued in accordance with standard of care.
Retreatment
If therapy is interrupted and there is a need to restart treatment with intravenous vedolizumab, dosing at every 4 weeks may be considered. The treatment interruption period in clinical trials extended up to 1 year. Efficacy was regained with no evident increase in adverse reactions or infusion-related reactions during retreatment with vedolizumab.
Pouchitis
The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter.
Treatment with vedolizumab should be initiated in parallel with standard of care antibiotic (e.g., four-week of ciprofloxacin).
Discontinuation of treatment should be considered if no evidence of therapeutic benefit is observed by 14 weeks of treatment with vedolizumab.
Retreatment
There are no retreatment data available in patients with pouchitis.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in SmPC.
Active severe infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis, and opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML)
Adverse effects
Summary of the safety profile
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory tract infection, bronchitis, influenza and sinusitis), headache, nausea, pyrexia, fatigue, cough, arthralgia.
Infusion related reactions (with symptoms such as dyspnoea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) have also been reported in patients treated with vedolizumab.
Tabulated list of adverse reactions
The following listing of adverse reactions is based on clinical trial and post marketing experience and is displayed by system organ class. Within the system organ classes, adverse reactions are listed under headings of the following frequency categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), very rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
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Table 1. Adverse reactions |
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|
System organ class |
Frequency |
Adverse reaction(s) |
|
Infections and infestations |
Very common |
Nasopharyngitis |
|
Common |
Pneumonia, Clostridium difficile infection, Bronchitis, Gastroenteritis, Upper respiratory tract infection, Influenza, Sinusitis, Pharyngitis, Herpes zoster |
|
|
Uncommon |
Respiratory tract infection, Vulvovaginal candidiasis, Oral candidiasis |
|
|
Immune system disorders |
Very rare |
Anaphylactic reaction, Anaphylactic shock |
|
Nervous system disorders |
Very common |
Headache |
|
Common |
Paraesthesia |
|
|
Eye disorders |
Uncommon |
Blurred vision |
|
Vascular disorders |
Common |
Hypertension |
|
Respiratory, thoracic and mediastinal disorders |
Common |
Oropharyngeal pain, Nasal congestion, Cough |
|
Not known |
Interstitial lung disease |
|
|
Gastrointestinal disorders |
Common |
Anal Abscess, Anal fissure, Nausea, Dyspepsia, Constipation, Abdominal distension, Flatulence, Haemorrhoids, Rectal haemorrhage* |
|
Hepatobiliary disorders |
Common |
Liver enzyme increased |
|
Very rare |
Hepatitis |
|
|
Skin and subcutaneous tissue disorders |
Common |
Rash, Pruritus, Eczema, Erythema, Night sweats, Acne |
|
Uncommon |
Folliculitis |
|
|
Musculoskeletal and connective tissue disorders |
Very common |
Arthralgia |
|
Common |
Muscle spasms, Back pain, Muscular weakness, Fatigue, Pain in the extremity |
|
|
General disorders and administration site conditions |
Common |
Pyrexia, Infusion related reaction (asthenia* and chest discomfort*), Infusion site reaction (including: Infusion site pain and Infusion site irritation) |
|
Uncommon |
Chills, Feeling cold |
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Interactions with other Drugs
No interaction studies have been performed.
Vedolizumab has been studied in adult ulcerative colitis and Crohn's disease patients with concomitant administration of corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate), and aminosalicylates. Population pharmacokinetic analyses suggest that co-administration of such agents did not have a clinically meaningful effect on vedolizumab pharmacokinetics.
In adult patients with pouchitis, vedolizumab has been co-administered with antibiotics. The pharmacokinetics of vedolizumab in patients with pouchitis has not been studied.
The effect of vedolizumab on the pharmacokinetics of commonly co-administered medicinal compounds has not been studied.
Vaccinations
Live vaccines, in particular live oral vaccines, should be used with caution concurrently with vedolizumab
Special situations
Women of childbearing potential
Women of childbearing potential should use adequate contraception to prevent pregnancy and to continue its use for at least 18 weeks after the last treatment.
Pregnancy
There are limited amount of data from the use of vedolizumab in pregnant women.
In a small prospective observational study the rate of major birth defects was 7.4% in 99 women with ulcerative colitis or Crohn's disease treated with vedolizumab and 5.6% in 76 women with ulcerative colitis or Crohn's disease treated with other biologic agents (adjusted relative risk (RR) 1.07, 95% Confidence Interval (CI): 0.33, 3.52).
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
As a precautionary measure, it is preferable to avoid the use of vedolizumab during pregnancy unless the benefits clearly outweigh any potential risk to both the mother and foetus.
Breast-feeding
Vedolizumab has been detected in human milk. The effect of vedolizumab on breast-fed infants and the effects on milk production are unknown. In a milk-only lactation study assessing the concentration of vedolizumab in breast milk of lactating women with active ulcerative colitis or Crohn's disease receiving vedolizumab, the concentration of vedolizumab in human breast milk was approximately 0.4% to 2.2% of the maternal serum concentration obtained from historical studies of vedolizumab. The estimated average daily dose of vedolizumab ingested by the infant was 0.02 mg/kg/day, which is approximately 21% of the body weight-adjusted average maternal daily dose.
The use of vedolizumab in lactating women should take into account the benefit of therapy to the mother and potential risks to the infant.
Fertility
There are no data on the effects of vedolizumab on human fertility. Effects on male and female fertility have not been formally evaluated in animal studies.