Safety and Efficacy of Subcutaneous Entyvio® (Vedolizumab) Sustained During Long-term Maintenance Therapy in Adults with Moderately to Severely Active Ulcerative Colitis
- Interim analysis from VISIBLE OLE study showed long-term findings consistent with the known safety profile of vedolizumab with maintained rates of clinical remission and corticosteroid-free clinical remission
Entyvio® was the first maintenance biological therapy approved across
Europein both intravenous (IV) and subcutaneous (SC) formulations to treat moderately to severely active ulcerative colitis or Crohn’s disease
- Latest data presented at the United European Gastroenterology Week (UEG Week) Virtual 2020 congress
VISIBLE OLE is an ongoing open-label, phase 3b, multinational, multicenter study to evaluate the long-term safety and tolerability of vedolizumab SC in adult patients with ulcerative colitis or Crohn’s disease (CD), following enrolment and participation in the VISIBLE 1 (UC) or VISIBLE 2 (CD) studies.1,2 Participants who completed the maintenance period up to week 52 (randomized completers), or who achieved clinical response at week 14 after a third vedolizumab IV infusion at week 6 (non-randomized week 14 responders), received vedolizumab SC 108 mg every two weeks.1,2 Interim data from the VISIBLE OLE study in the UC patient population demonstrated that adverse events were consistent with the known safety profile of vedolizumab.1 During two years of maintenance treatment, adverse events occurred in 69% of patients with UC, with disease exacerbations (18%), nasopharyngitis (11%), upper respiratory tract infection (9%), and anemia (7%) reported most frequently.1 Injection site reactions were reported in 4.5% of patients and all were mild or moderate in severity.1 Serious adverse events occurred in 14% of patients, with no cases of progressive multifocal leukoencephalopathy and no deaths.1
In randomized completers, rates of clinical remission and corticosteroid-free clinical remission were maintained up to week 108 (week 6: 71.0% [n=49/69] and week 108: 68.9% [n=42/61], respectively; week 52: 78.3% [n=18/23] to week 108: 70.0% [n=14/20], respectively).1 In non-randomized week 14 responders, the comparative rates were 62.6% [n=67/107] at week 14 and 33.3% [n=31/93] at week 110 for clinical remission, and 24.5% [n=12/49] at week 54 and 25.0% [n=11/44] at week 110 for corticosteroid-free clinical remission.1
“These latest safety and effectiveness data for vedolizumab SC provide additional support/data that the benefits received from subcutaneous vedolizumab are sustained during long-term maintenance therapy,” said
* Clinical remission is defined as a partial Mayo score of ≤2 with no individual subscore >1 point1
** Corticosteroid-free clinical remission is defined as patients using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission1
About the VISIBLE Clinical Trial Program
The VISIBLE clinical trial program aims to assess the efficacy and safety of a subcutaneous (SC) formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD).
The VISIBLE program consists of three phase 3 studies involving over 1,000 UC and CD patients which includes two randomized, double-blind, placebo-controlled studies examining the proportion of patients achieving clinical remission at week 52, and an open-label extension study to determine the long-term safety and efficacy of vedolizumab SC.2,3,4
About Ulcerative Colitis and Crohn’s Disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are two of the most common forms of inflammatory bowel disease (IBD).5 Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract, with CD potentially progressing over time.6,7 UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus.8,9 CD can also affect the entire thickness of the bowel wall while UC only involves the innermost lining of the large intestine.8,9 UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus.8,10 CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss.6 The cause of UC or CD is not fully understood; however, recent research suggests hereditary, genetics, environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC or CD.8,11,12
About Entyvio® (vedolizumab)
Vedolizumab is a gut-selective biologic and is approved in both intravenous (IV) and subcutaneous (SC) formulations.13,14 The SC formulation is currently approved in
Vedolizumab is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα)-antagonist.13,14 Vedolizumab has been granted marketing authorization in over 70 countries, including the
Therapeutic Indications for vedolizumab
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 tumor necrosis factor-alpha (TNFα) antagonist.
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 tumor necrosis factor-alpha (TNFα) antagonist.
Important Safety Information for vedolizumab
Hypersensitivity to the active substance or to any of the excipients.
Special warnings and special precautions for use
Intravenous vedolizumab should be administered by a healthcare professional prepared to manage hypersensitivity reactions, including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering intravenous vedolizumab. Observe patients during infusion and until the infusion is complete.
Infusion-related reactions and Hypersensitivity Reactions
In clinical studies, infusion-related reactions (IRR) and hypersensitivity reactions have been reported, with the majority being mild to moderate in severity. If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of vedolizumab must be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines). If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate treatment initiated (e.g., epinephrine and antihistamines). Once the mild or moderate IRR subsides, continue the infusion. Physicians should consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next infusion for patients with a history of mild to moderate IRR to vedolizumab, in order to minimize their risks.
Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive activity. Physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Vedolizumab treatment is not to be initiated in patients with active, severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections until the infections are controlled, and physicians should consider withholding treatment in patients who develop a severe infection while on chronic treatment with vedolizumab. Caution should be exercised when considering the use of vedolizumab in patients with a controlled chronic severe infection or a history of recurring severe infections. Patients should be monitored closely for infections before, during and after treatment. Before starting treatment with vedolizumab, screening for tuberculosis may be considered according to local practice. Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy (PML), which is a rare and often fatal opportunistic infection caused by the John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect specific to the gut. No systemic immunosuppressive effect was noted in healthy subjects. Healthcare professionals should monitor patients on vedolizumab for any new onset or worsening of neurological signs and symptoms, and consider neurological referral if they occur. If PML is suspected, treatment with vedolizumab must be withheld; if confirmed, treatment must be permanently discontinued. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months.
The risk of malignancy is increased in patients with ulcerative colitis and Crohn’s disease. Immunomodulatory medicinal products may increase the risk of malignancy.
Prior and concurrent use of biological products
No vedolizumab clinical trial data are available for patients previously treated with natalizumab. No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are available. Therefore, the use of vedolizumab in such patients is not recommended.
Prior to initiating treatment with vedolizumab all patients should be brought up to date with all recommended immunizations. Patients receiving vedolizumab may receive non-live vaccines (e.g., subunit or inactivated vaccines) and may receive live vaccines only if the benefits outweigh the risks.
Adverse reactions include: nasopharyngitis, headache, arthralgia, upper respiratory tract infection, bronchitis, influenza, sinusitis, cough, oropharyngeal pain, nausea, rash, pruritus, back pain, pain in extremities, pyrexia, fatigue, injection site reactions and anaphylaxis.
Injection Site Reactions (subcutaneous vedolizumab)
No clinically relevant differences in the overall safety profile and adverse events were observed in patients who received subcutaneous vedolizumab compared to the safety profile observed in clinical studies with intravenous vedolizumab with the exception of injection site reactions (with subcutaneous administration only). Injection-site reactions were mild or moderate in intensity, and none were reported as serious.
Please consult with your local regulatory agency for approved labeling in your country.
For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.
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2 Vedolizumab Subcutaneous Long-Term Open-Label Extension Study. Available at: https://clinicaltrials.gov/ct2/show/NCT02620046 Last updated:
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4 Efficacy and safety of vedolizumab subcutaneous (SC) as maintenance therapy in Crohn's disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02611817. Last updated:
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14 Entyvio EPAR _
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