For adults with moderate to severe ulcerative colitis
ENTYVIO Pen for subcutaneous administration
US-VED-2488v1.0 10/23
Get to know Entyvio's
Proven safety
profile based on
4 clinical trials
ENTYVIO
vs
placebo1
>3300 adults (UC,
Crohn's, and healthy
volunteers)
Clinical
trials
ENTYVIO
7-year
safety data2,3
Single-arm,
open-label study
7999 patient-
years of
exposure
Head-to-head trial4
ENTYVIO vs Humira®
(adalimumab)
Not designed
to assess
safety
differences
ENTYVIO SC1,5
Consistent safety
profiles in UC
With the
exception of
injection site
reactions
SC=subcutaneous.
For adult patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) when other therapies have not worked well enough or cannot be tolerated.
Adverse reactions observed in the GEMINI trials
Adverse reactions in ≥3% of ENTYVIO-treated patients and ≥1% higher than in placebo (UC Trials I and II* and Crohn's Trials I and III*)1
*Data from patients receiving open-label ENTYVIO treatment at Weeks 0 and 2 (prior to entry into UC Trial II and Crohn's Trial III) and from Weeks 6 to 52 (non-responders at Week 6 of UC Trial I and Crohn's Trial I) are included.
†Patients who received ENTYVIO for up to 52 weeks.
‡Patients who received placebo for up to 52 weeks.
Adverse events based on Ulcerative Colitis Trials I and II and Crohn’s Disease Trials I and III1
INFECTIONS
- Infection rates with ENTYVIO were 0.85 per patient-year vs 0.7 for placebo
- Infections consisted primarily of nasopharyngitis, upper respiratory tract infection, sinusitis, and urinary tract infection
- 2% of patients discontinued ENTYVIO due to infections
SERIOUS INFECTIONS
- Serious infection rates with ENTYVIO were 0.07 per patient-year vs 0.06 for placebo
- Serious infections included anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis
IMMUNOGENICITY
- The rate of detectable anti-vedolizumab antibodies at any time during the 52 weeks of continuous treatment with ENTYVIO was 6% (86 of 1427 patients)
- 20 of 86 patients were persistently positive (at 2 or more study visits) for anti-vedolizumab antibodies, and 56 of 86 patients developed neutralizing antibodies to vedolizumab
- Among these 20 patients, 14 had undetectable or reduced vedolizumab serum concentrations. Five of the 20 patients with persistently positive anti-vedolizumab antibodies achieved clinical remission at Week 52 in the controlled trials
- Overall, there was no apparent correlation of anti-vedolizumab antibody development to adverse reactions following intravenous administration of ENTYVIO
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
- Although unlikely, a risk of PML cannot be ruled out:
- PML, a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML is caused by the John Cunningham (JC) virus and typically only occurs in patients who are immunocompromised
- 1 case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported in the postmarketing setting (eg, human immunodeficiency virus [HIV] infection with a CD4 count of 300 cells/mm3 and prior and concomitant immunosuppression)
LIVER INJURY
- ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury
- 3 patients reported serious adverse reactions of hepatitis with ENTYVIO; 1 additional case of serious hepatitis was seen in the open-label trial
- These adverse reactions occurred following 2 to 5 ENTYVIO doses; however, it is unclear if the reactions indicated drug-induced or autoimmune etiology
- There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO
- All patients recovered following discontinuation of therapy with or without treatment with corticosteroids
MALIGNANCIES
- Malignancies (excluding dysplasia and basal cell carcinoma) were observed in 0.4% (6 of 1434) of patients treated with ENTYVIO and in 0.3% (1 of 297) of patients treated with placebo
- The number of malignancies in clinical trials was small; however, long-term exposure was limited
ADVERSE REACTIONS
- Adverse reactions were reported in 52% of patients treated with ENTYVIO (N=1434) and 45% of patients treated with placebo (N=297)
- Over 52 weeks, serious adverse reactions were reported in 7% of patients treated with ENTYVIO compared to 4% treated with placebo
INFUSION-RELATED REACTIONS (IRRs) AND HYPERSENSITIVITY REACTIONS
- 4% of patients treated with ENTYVIO (N=1434) experienced an IRR vs 3% of patients on placebo (N=297)
- 1 case of anaphylaxis (1 of 1434 patients treated with ENTYVIO) was reported by a Crohn’s disease patient during the second infusion (symptoms reported were dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) and was managed with discontinuation of infusion and treatment with antihistamine and IV hydrocortisone
- Most frequently observed IRRs in patients treated with ENTYVIO were nausea, headache, pruritus, dizziness, fatigue, infusion-related reaction, pyrexia, urticaria, and vomiting. These reactions generally occurred within the first 2 hours after the infusion and resolved with no treatment or following antihistamine and/or IV hydrocortisone treatment
Up to 7 years of consistent results across safety parameters1-3*
Clinical trials evaluated safety in more than 3300 adults (UC, Crohn’s, and healthy volunteers).1
*In a separate, single-arm, open-label extension study, 2243 patients received ENTYVIO with a median exposure of 1072 days (range 1 to 3412 days).2,3
GEMINI long-term safety study design2
- GEMINI Long-term Safety Study was a phase 3, single-arm, open-label, multinational study evaluating the long-term safety profile of ENTYVIO in patients with moderately to severely active ulcerative colitis or Crohn’s disease
- Patients were enrolled from GEMINI 1, GEMINI 2, GEMINI 3, a long-term phase 2 study, and a cohort of ENTYVIO-naïve patients with ulcerative colitis or Crohn’s disease
- The safety population included all patients who received any dose of ENTYVIO
- Data were collected from May 2009 to October 2017
- The study evaluated 2243 patients with ulcerative colitis or Crohn’s disease who received ENTYVIO for a median of 42.4 months for ulcerative colitis (range 0.03 to 112.2 months) and 31.5 months for Crohn’s disease (range 0.03 to 100.3 months)
Length of exposure to ENTYVIO in the long-term safety study2,3
Exposure-adjusted incidence rates of selected AEs in the GEMINI long-term safety study2*
*Time-adjusted incidence rate per 1000 PYs=(number of patients experiencing an adverse event of interest/total person time in years) x 1000.2
†Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms.1
AE=adverse event; PML=progressive multifocal leukoencephalopathy; PY=patient-year.
No new signals of 2,3
- Infections
- Malignancies
- Infusion-related reactions
- Hepatic injury
Adverse events observed in the VARSITY trial
Safety was evaluated in 383 patients
no new safety
signals
were observed for
ENTYVIO3,4,6
Study was not designed to assess safety differences
The most frequent AEs for Humira® and ENTYVIO were as follows: ≥1 TEAE, 35.8% and 32.9%; UC, 16.3% and 11.5%; nasopharyngitis, 7.8% and 7.0%; headache, 5.4% and 7.0%; anemia, 6.7% and 5.2%; abdominal pain, 5.2% and 4.7%; upper respiratory tract infection, 4.4% and 5.2%†
*Humira® is a registered trademark of AbbVie Inc., North Chicago, IL. For information about Humira®, please see AbbVie.com.
†Adverse events that occurred during the trial period. Trial period was the time from the first dose of a trial drug and up to 126 days after the last dose. Adverse events were classified according to the Medical Dictionary for Regulatory Activities System Organ Class categorization and preferred terms (version 21.0). The safety population was defined as all patients who received at least 1 dose of the study drug.
‡No cases of progressive multifocal leukoencephalopathy.
§Not related to ENTYVIO.
||Updated to include final 68-week safety follow-up.
AE=adverse event; TEAE=treatment-emergent adverse event.
Adverse events observed in the visible 1 trial
ENTYVIO Pen for subcutaneous administration is only
approved for adults with moderate to severe UC.
ENTYVIO subcutaneous and IV demonstrated
similar overall safety profiles, with the exception of injection site reactions1,5
No formal statistical comparisons were made between ENTYVIO SC and IV arms within the VISIBLE 1 trial or between the VISIBLE 1 and GEMINI I trials.
Most frequent (≥5% in any treatment group) adverse events5*
- Immunogenicity: incidence of anti-drug antibodies with ENTYVIO SC was similar to that reported with ENTYVIO IV at 6%
Injection site reactions (ISRs)1,5
- ISRs were reported in 9% (10/106) of patients receiving ENTYVIO SC
- ISRs including injection site erythema, rash, swelling, bruising, and hematoma were not reported as serious AEs
- ISRs did not lead to discontinuation of, or changes to, the study medication dose
*The safety analysis set included all patients who were randomized to the maintenance phase and received at least 1 dose of the study drug.
Explore more topics
See efficacy data in ulcerative colitis
See efficacy data in Crohn’s disease
The content on this page has been written and
reviewed by Takeda.
IMPORTANT SAFETY INFORMATION
Contraindications
ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.
WARNINGS AND PRECAUTIONS
- Infusion-Related and Hypersensitivity Reactions: Infusion-related reactions and hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart
IMPORTANT SAFETY INFORMATION
Contraindications
ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.
Warnings and precautions
- Infusion-Related and Hypersensitivity Reactions: Infusion-related reactions and hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have been reported. These reactions may occur with the first or subsequent infusions and may vary in their time of onset from during infusion or up to several hours post-infusion. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
- Infections: Patients treated with ENTYVIO are at increased risk for developing infections. Serious infections have been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution in patients with a history of recurring severe infections. Consider screening for tuberculosis (TB) according to the local practice.
- Progressive Multifocal Leukoencephalopathy (PML): PML, a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported. Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms that may include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. If PML is suspected, withhold dosing with ENTYVIO and refer to neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
- Liver Injury: There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury.
- Live and Oral Vaccines: Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines. Patients receiving ENTYVIO may receive non-live vaccines and may receive live vaccines if the benefits outweigh the risks.
Adverse reactions
The most common adverse reactions (incidence ≥3% and ≥1% higher than placebo) were: nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, pain in extremities, and injection site reactions with subcutaneous administration.
Drug interactions
Because of the potential for increased risk of PML and other infections, avoid the concomitant use of ENTYVIO with natalizumab products and with TNF blockers.
INDICATIONS
Adult Ulcerative Colitis (UC):
ENTYVIO is indicated in adults for the treatment of moderately to severely active UC.
Adult Crohn’s Disease (CD):
ENTYVIO is indicated in adults for the treatment of moderately to severely active CD.
Dosage forms & strengths:
- ENTYVIO Intravenous (IV) Infusion: 300 mg vedolizumab
- ENTYVIO Subcutaneous (SC) Injection: 108 mg vedolizumab
Please click for Full Prescribing Information.
References:
- ENTYVIO (vedolizumab) prescribing information. Takeda Pharmaceuticals.
- Loftus EV Jr, Feagan BG, Panaccione R, et al; for the GEMINI LTS study team. Long-term safety of vedolizumab for inflammatory bowel disease. Aliment Pharmacol Ther. 2020;52(8):1353-1365.
- Data on File. Takeda Pharmaceuticals.
- Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. Vedolizumab versus adalimumab for moderate-to-severe ulcerative colitis. N Engl J Med. 2019;381(13):1215-1226.
- Sandborn WJ, Baert F, Danese S, et al. Efficacy and safety of vedolizumab subcutaneous formulation in a randomized trial of patients with ulcerative colitis. Gastroenterology. 2020;158(3):562-572.e12.
- Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. Vedolizumab versus adalimumab for moderate-to-severe ulcerative colitis. N Engl J Med. 2019;381(13):1215-1226 (supplemental appendix).
