For U.S. Healthcare Professionals

Safety
For the

For adult patients with moderately to severely active UC or CD when other therapies have not worked well enough or cannot be tolerated.
LONG‑TERM SAFETY PROFILE
2014
Clinical trials evaluated safety in more than 3300 adults (UC, CD, and healthy volunteers)1
2017
5-Year Open Label
5-year analysis, which included an open-label continuation study (UC and CD), has demonstrated consistent results across safety parameters2
2019
Study was not designed to assess safety differences
2020
A single arm, open-label, multinational study evaluated the long-term safety profile of Entyvio in moderately to severely active UC or CD patients.3
- The study evaluated 2243 patients who received Entyvio with a median exposure of 1072 days (range 1 to 3412 days)3-5
Entyvio demonstrated up to 7 years of consistent results across safety parameters3-5
UC TRIALS I & II AND CD TRIALS I & III
SELECT ADVERSE EVENTS1

ADVERSE EVENTS BASED ON UC TRIALS I AND II, CD 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 antibody, 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 antibody 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 (e.g., 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 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, 7% of patients treated with Entyvio experienced serious adverse reactions 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 CD 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 two hours after the infusion and resolved with no treatment or following antihistamine and/or IV hydrocortisone treatment
NOW UP TO 7 YEARS OF CONSISTENT SAFETY DATA IN UC AND CD3-5
STUDY DESIGN/METHODOLOGY
- GEMINI LTS 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 UC or CD
- Patients were enrolled from the phase 3 studies GEMINI 1, GEMINI 2, GEMINI 3, a long-term phase 2 study, and included a cohort of Entyvio-naive patients with UC and CD. Data were collected from May 2009 to October 2017
- The study evaluated 2243 UC and CD patients who received Entyvio with a median exposure of 42.4 months for UC (range 0.03 to 112.2 months) and 31.5 months for CD (range 0.03 to 100.3 months)
- The safety population included all patients who received any dose of Entyvio
BASELINE CHARACTERISTICS

MEDIAN ENTYVIO EXPOSURE IN CD: 31.5 MONTHS, RANGE 0.03–100.3 MONTHS
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LTS = long-term safety.
Exposure-adjusted incidence rates
of any AE or SAE
event/1000 PYs of exposure*

* Time-adjusted incidence rate per 1000 PYs = (number of patients experiencing an AE of interest/total person time in years) x 1000.
Open-label study up to 7 years demonstrated a consistent safety profile in UC and CD patients
- The most frequent AEs were disease exacerbations (35.9% UC, 35.3% CD), nasopharyngitis (28.2% UC, 25.4% CD) and arthralgia (17.3% UC, 24.4% CD)
- 39.7% of AEs in UC and 46.2% of AEs in CD were considered by the treating physician to be related to exposure to Entyvio
NO NEW SIGNALS OF:
- Infections
- Malignancies
- Infusion-related reactions
- Hepatic injury
Exposure-adjusted incidence rates of selected AEs

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* Time-adjusted incidence rate per 1000 PYs = (number of patients experiencing an AE of interest/total person time in years) x 1000.
† Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms.1
No new safety signals up to 7 years in UC and CD patients
- GEMINI LTS identified no cases of PML with 7999 PYs of Entyvio exposure†
AE = adverse event; LTS = long-term safety; PML = progressive multifocal leukoencephalopathy; PY = patient year; SAE = serious adverse event.
ADVERSE EVENTS OBSERVED IN THE VARSITY STUDY
Safety Was Evaluated in 383 Patients: No New Safety Signals Were Observed for Entyvio6-8
STUDY WAS NOT DESIGNED TO ASSESS SAFETY DIFFERENCES

ADVERSE EVENTS IN SAFETY POPULATION
- The most frequent AEs* for adalimumab and Entyvio were as follows: ≥1 TEAE, 35.8% and 32.9%; ulcerative colitis, 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%
* 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 one 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.
Crohn's Disease Data
SEE RESULTS IN CDDosing & Administration
REVIEW THE GUIDANCEReferences:
- Entyvio (vedolizumab) prescribing information. Takeda Pharmaceuticals.
- Colombel JF, Sands BE, Rutgeerts P, et al. Gut. 2017;66(5):839-851.
- Loftus EV, Feagan BG, Panaccione R, et al; for the GEMINI LTS study team. Aliment Pharmacol Ther. 2020;00:1-13.
- Data on file. MLN0002, Final CSR C13008, July 2018. Takeda Pharmaceuticals USA, Inc.
- Data on file. Internal communication, October 2020. Takeda Pharmaceuticals USA, Inc.
- Data on file. Internal communication, November 2019. Takeda Pharmaceuticals USA, Inc.
- Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. N Engl J Med. 2019;381(13):1215-1226.
- Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. N Engl J Med. 2019;381(13):1215-1226. (supplemental appendix).