Clinical UM Guideline

 

Subject: Vedolizumab (Entyvio®)
Guideline #: CG-DRUG-87 Publish Date:    12/12/2018
Status: Reviewed Last Review Date:    11/08/2018

Description

This document addresses the U.S. Food and Drug Administration (FDA) approved indications for vedolizumab (Entyvio, Millennium Pharmaceuticals Inc., Takeda Pharmaceuticals America, Inc.), an integrin receptor antagonist used for the treatment of moderately to severely active Crohn’s disease and moderately to severely active ulcerative colitis.

Note: Please see the following documents for information concerning other drugs that may be used for the treatment of Crohn’s disease and ulcerative colitis:

Clinical Indications

Medically Necessary:

Vedolizumab is considered medically necessary when criteria are met for either of the following indications:

  1. Crohn’s disease when the following criteria are met:
    1. Individual is 6 years of age or older with moderately to severely active Crohn’s disease; and
    2. Individual has failed to respond to, lost response to, is intolerant of, or has a medical contraindication to either of the following:
      1. A tumor necrosis factor (TNF) antagonist drug; or
      2. Conventional drug therapy, such as aminosalicylates/5-ASA products (for example, mesalamine, sulfasalazine), an immunomodulator (for example, azathioprine, 6-mercaptopurine [6-MP], or an immunosuppressive drug); or
    3. Individual has failed to respond to, is intolerant of, or has demonstrated dependence on systemic corticosteroids; and
    4. Vedolizumab is used for one of the following:
      1. To reduce signs or symptoms; or
      2. To induce or maintain clinical response or remission.
  2. Ulcerative colitis when the following criteria are met:
    1. Individual is 6 years of age or older with moderately to severely active ulcerative colitis; and
    2. Individual has failed to respond to, lost response to, is intolerant of, or has a medical contraindication to either of the following:
      1. A TNF antagonist drug; or
      2. Conventional drug therapy, such as aminosalicylates/5-ASA products (for example, mesalamine, sulfasalazine), an immunomodulator (for example, azathioprine, 6-MP, or an immunosuppressive drug); or 
    3. Individual has failed to respond to, is intolerant of, or has demonstrated dependence on systemic corticosteroids; and
    4. Vedolizumab is used for one of the following:
      1. To reduce signs or symptoms; or
      2. To induce or maintain clinical remission or response and mucosal healing.

Not Medically Necessary:

Vedolizumab is considered not medically necessary for an individual with any of the following:

  1. In combination with a TNF antagonist; or
  2. In combination with a non-TNF antagonist immunomodulator drug, such as natalizumab (Tysabri®, Biogen Idec Inc., Cambridge, MA; Elan Pharmaceuticals, Inc., San Diego, CA); or
  3. Active, serious infection or a history of recurrent infections; or
  4. New or worsening neurological signs or symptoms of John Cunningham virus (JCV) infection or risk of progressive multifocal leukoencephalopathy (PML).

Vedolizumab is considered not medically necessary when criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J3380

Injection, vedolizumab, 1 mg [Entyvio]

 

 

ICD-10 Diagnosis

 

 

K50.00-K50.919

Crohn’s disease (regional enteritis)

 

K51.00-K51.919

Ulcerative colitis

 

Discussion/General Information

Crohn’s disease and ulcerative colitis are chronic, relapsing inflammatory bowel diseases (IBD) affecting the gastrointestinal mucosa. Crohn’s disease, also referred to as regional enteritis, is an IBD generally accepted as an autoimmune disease that occurs in genetically predisposed individuals; clinical presentation is primarily determined by the anatomic location of the disease. The most common presenting symptoms are fever, abdominal pain, and diarrhea with or without blood. Fistula formation, fissuring, discontinuous intestinal and transmural involvement with bowel-wall thickening and extraintestinal manifestations such as arthritis, skin and eye manifestations, metabolic deficiencies, hypercoagulation, and hepatobiliary disease are frequent complications. The clinical course of Crohn’s disease is chronic and intermittent and there is no known cure. Medical therapy includes the use of 5-ASA products such as mesalamine, sulfasalazine, or olsalazine, glucocorticoids such as prednisone or budesonide, antibiotics, immunosuppressive drugs (6-MP/AZA), methotrexate and targeted immune modulator agents.

Ulcerative colitis is a chronic disease characterized by diffuse mucosal inflammation limited to the colon and may affect any age group. Besides the primary clinical symptom of bloody diarrhea, ulcerative colitis is often accompanied by symptoms of rectal urgency and painful, unsuccessful attempts to have a bowel movement. The clinical course is marked by intermittent worsening or slowing of disease symptoms. Conventional treatment options for individuals with severe corticosteroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently limited by toxicity, certain TNF antagonist agents, or in ulcerative colitis unresponsive to pharmacologic agents, surgical resection (for example, colectomy).

Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin (a cell-adhesion molecule), blocks the interaction of α4β7 integrin with mucosal addressing cell adhesion molecule-1 (MAdCAM-1), and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal mucosa. The interaction of the α4β7 integrin with MAdCAM-1 has been identified as an important contributor to the chronic inflammation of Crohn’s disease and ulcerative colitis.

On May 20, 2014, the FDA approved vedolizumab (Entyvio, Takeda Pharmaceuticals America, Inc., Deerfield, IL) for two indications: treatment of adults with either moderately to severely active Crohn’s disease or moderately to severely active ulcerative colitis who have not fully responded to treatment with steroids, immunomodulators, or TNF inhibitors (antagonists).

Efficacy of Vedolizumab for Crohn’s Disease

The FDA approval of vedolizumab for active Crohn’s disease was confirmed in two pivotal trials, GEMINI 2 and GEMINI 3. The GEMINI 2 trial (Sandborn, 2013) is a placebo-controlled, induction-maintenance phase 3 trial in adults 18 years of age or older with active Crohn’s disease for at least 3 months with a Crohn’s Disease Activity Index (CDAI) score of 220 to 450 (that is, moderate to severe disease). GEMINI 3 (Sands, 2014) is a randomized, placebo-controlled, double-blind 6-week trial of induction therapy in adults 18 years of age or older with moderately to severely active Crohn’s disease who failed to respond to, or were intolerant to prior therapy.

At week 6 in the induction phase of GEMINI 2, rates of clinical remission (primary induction end point defined as CDAI score ≤ 150) differed significantly (p=0.02) in the vedolizumab- versus placebo-treated participants (15%, 7%, and 17.7% in the vedolizumab arm of cohort 1, placebo arm of cohort 1, and cohort 2 [all participants received vedolizumab], respectively). There were no statistical differences in CDAI-100 response (that is, ≥ 100 point decrease in CDAI score, primary induction end point) or change in C-reactive protein (CRP) levels from baseline to week 6 (a secondary induction end point). At week 52 in the maintenance phase of GEMINI 2, rates of clinical remission (primary maintenance end point) differed significantly in participants treated with both regimens of vedolizumab versus those treated with placebo. Rates of clinical remission were 39.0% versus 21.6% in the vedolizumab every 8 weeks arm compared to the placebo arm, respectively (p<0.001); and, 36.4% versus 21.6% in the vedolizumab every 4 weeks arm compared to the placebo arm, respectively (p=0.004). Secondary maintenance end points such as CDAI-100 response at 52 weeks and glucocorticoid-free remission (but not durable remission) met the statistical threshold of < 0.05. In the induction phase only in GEMINI 3 (Sands, 2014), the primary end point, that is, clinical remission at week 6 in participants with prior TNF antagonist agent failure, was not met: 15% in the vedolizumab-treated group versus 12% in the placebo group (p=0.433). At week 10, however, a higher proportion of the vedolizumab-treated participants were in remission (26.6%) than those given placebo (12.1%) (nominal p=0.001; relative risk [RR], 2.2; 95% confidence interval [CI], 1.3-3.6). A higher proportion of participants with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥ 100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs. 22.3%; nominal p=0.001; RR, 1.8; 95% CI, 1.2-2.5). Exploratory analyses of planned secondary end points suggested a beneficial effect of vedolizumab in clinical remission at 10 weeks. Adverse event results were similar among all groups.

In 2018, Schreiber and colleagues published a meta-analysis of observational studies (registry studies and medical record reviews) evaluating vedolizumab in individuals with IBD. A meta-analysis of 11 studies (total of 796 individuals) on Crohn’s disease found a 14-week remission rate after treatment with vedolizumab of 30% (95% CI: 25 to 34%).  The remission rate at 12 months (7 studies, total of 595 individuals) was 30% (95% CI: 20 to 42%).  The analysis was limited by lack of a placebo or active control group.

Efficacy of Vedolizumab for Ulcerative Colitis

The FDA approval of vedolizumab for ulcerative colitis was confirmed in a placebo-controlled, induction-maintenance phase 3 trial of adults ages 18 years or older with active disease (Feagan, 2013). The study design of the GEMINI 1 UC trial was similar to GEMINI 2 (CD trial) in that participants were recruited from 2 cohorts in the induction phase, a double-blind cohort 1 phase (vedolizumab, n=225; placebo, n=149) and an open-label cohort 2 phase (n=521) of participants who received vedolizumab induction therapy. In the maintenance phase (at week 6), participants with a clinical response to induction (that is, a reduction in the Mayo score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the Rectal Bleeding subscale or an absolute rectal bleeding score of 0 or 1) from both cohorts were re-randomized to placebo (n=126), vedolizumab 300 mg intravenous (IV) every 8 weeks (n=122), or vedolizumab 300 mg IV every 4 weeks (n=125) for 52 weeks.

At week 6, rates of clinical response (primary induction end point) in the induction phase differed significantly (p<0.001) in vedolizumab- versus placebo-treated participants, that is, 47.1%, 25.5%, and 44.3% in the vedolizumab arm of cohort 1, placebo arm of cohort 1, and cohort 2 [all participants received vedolizumab], respectively). Both secondary induction end points (clinical remission and mucosal healing at week 6) were statistically and significantly higher in vedolizumab- versus placebo-treated participants. At week 52, rates of clinical remission (primary maintenance end point) differed significantly in participants treated with both regimens of vedolizumab versus those treated with placebo. Rates of clinical remission were 41.8% versus 15.9% in the vedolizumab every 8 weeks compared to the placebo arm, respectively (p<0.001); and, 44.8% versus 15.9% in the vedolizumab every 4 weeks compared to the placebo arm, respectively (p<0.001). At 52 weeks, durable clinical response and remission, mucosal healing, and glucocorticoid-free remission met the statistical threshold (< 0.05).

The 2018 meta-analysis of observational studies on vedolizumab, discussed above (Schreiber, 2018), reported remission rates after treatment for ulcerative colitis.  A meta-analysis of 6 studies (total of 463 individuals) found a 14-week remission rate after treatment with vedolizumab of 32% (95% CI: 27 to 39%).  The remission rate at 12 months (7 studies, total of 454 individuals) was 46% (95% CI: 37 to 56%).  As noted above in the section on Crohn’s disease, the analysis was limited by lack of a placebo or active control.

Safety of Vedolizumab for Crohn’s Disease and Ulcerative Colitis

In the clinical trials of vedolizumab for active Crohn’s disease and active ulcerative colitis, participants were monitored for progressive multifocal leukoencephalopathy (PML). Although no cases were observed in the trials, John Cunningham virus (JCV) infection resulting in PML and death has occurred in individuals treated with another integrin receptor antagonist (that is, natalizumab). According to the PI label (2018), a risk of PML cannot be ruled out; therefore, individuals treated with vedolizumab for Crohn’s disease and ulcerative colitis should be monitored for any new or worsening neurological signs or symptoms. In the CD trials, vedolizumab was associated with a higher rate of serious adverse events (24% vs. 15%) and serious infections (5% vs. 3%) compared with placebo. Serious adverse reactions reported in the combined data set in the clinical trials were 7% for vedolizumab-treated participants versus 4% for placebo-treated participants. The most common adverse reactions to vedolizumab were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritis, sinusitis, oropharyngeal pain, and pain in the extremities.

Colombel and colleagues (2016) evaluated the safety data from six clinical trials of vedolizumab for ulcerative colitis and Crohn's disease. Adverse events were evaluated in participants who received ≥ one dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates (that is, the number of participants experiencing the event per 100 person-years of exposure). Predictors of serious infection were assessed using a Cox proportional hazards model. A total of 2830 participants had 4811 person-years of vedolizumab exposure (median exposure range, 1-1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections (n=15), sepsis (n=11), tuberculosis (n=4), and Listeria meningitis (n=1) were reported for between 1 and 15 participants (≤ 0.6% of participants). No cases of PML were observed. Independent risk factors for serious infection in participants with ulcerative colitis were prior failure of a TNF antagonist (Hazard ratio [HR], 1.99; 95% CI 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003). In Crohn’s disease participants, independent risk factors for serious infection were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p<0.0001) and corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p<0.0001). Infusion-related reactions (as defined by the investigators) were reported for ≤ 5% of participants in each study. A total of 18 vedolizumab-exposed participants (< 1%) were diagnosed with a malignancy.

The American Gastrological Association (AGA) Ulcerative Colitis Critical Care Pathway lists vedolizumab after steroids and anti-TNF inhibitors as a recommended induction therapy for high-risk individuals with ulcerative colitis.  In addition, vedolizumab is recommended for high-risk individuals not in remission who fail to respond to other therapies.

Summary

Several systematic reviews and meta-analyses including only placebo-controlled trials have indirectly compared vedolizumab with other biologic agents (Chandar, 2015; Danese, 2014; Hazelwood, 2014; Lin, 2015; Singh, 2014). To date, there are no published randomized controlled clinical trials that directly compare vedolizumab to other biologic agents for the treatment of active Crohn’s disease or active ulcerative colitis.

Off-Label Use of Vedolizumab in the Pediatric Population with Crohn’s Disease and Ulcerative Colitis

Conrad and colleagues (2016) performed a single-center, observational, prospective cohort study of 21 children ages 13 to 21 years with severe IBD, including Crohn’s disease (n=16), ulcerative colitis (n=3), or IBD unclassified (IBD-U) (n=2), who were refractory to TNF antagonist therapy. Subjects were selected for study inclusion by the treating pediatric gastroenterologist. Nearly half of the Crohn’s disease subjects had complicated disease, including 3 subjects with stricturing disease, 2 subjects with penetrating disease, and 2 subjects with both stricturing and penetrating disease. All subjects were treated with at least one TNF antagonist agent before starting vedolizumab, and 13 of 21 (62%) subjects had failed treatment with two TNF antagonist agents. Vedolizumab therapy was initiated in all subjects at an induction dose of 300 mg infusions at 0, 2, and 6 weeks followed by a maintenance phase at 8-week intervals. Concomitant medications were prescribed at the discretion of the treating pediatric gastroenterologist. Disease activity, clinical response, concomitant medication use and adverse events were measured over 22 weeks. Pediatric Crohn’s Disease Activity Index (PCDAI) or Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at each infusion visit based on history and physical examination performed by a physician member of the study team, and laboratory data extracted from the electronic medical record. Clinical response (combined PCDAI and PUCAI disease activity) was observed in 6 of 19 (31.6%) evaluable subjects at week 6 and in 11 of 19 (57.9%) evaluable subjects by week 22. Before induction, 15 of 21 (71.4%) subjects were treated with systemic corticosteroids compared with 7 of 21 (33.3%) subjects at 22 weeks. Steroid-free remission was obtained by 1 of 20 (5.0%) subjects at 6 weeks, 3 of 20 (15.0%) subjects at 14 weeks, and 4 of 20 (20.0%) subjects at 22 weeks. A statistically significant improvement in serum albumin and hematocrit was observed; however, CRP increased by week 22 (p<0.05). No infusion reactions were reported. There were five occurrences of upper respiratory tract infections, fatigue, nausea, vomiting, headaches, dizziness, nasopharyngitis, erythema nodosum, skin infections, new perianal disease, and sinusitis at follow-up visits. A total of 12 serious adverse events resulted in hospitalization among the subjects receiving vedolizumab during the study period. Two subjects required surgery, including 1 subject with ulcerative colitis who had persistent symptoms of severe colitis and steroid dependence and required a total colectomy shortly after the week 22 infusion. The second subject with Crohn’s disease had a history of recurrent acute kidney injury due to hypovolemia with disease flares and developed obstructing nephrolithiasis with associated pyonephritis. This subject required surgical intervention, antibiotic treatment, and continued on vedolizumab, subsequently achieving remission without further renal involvement. Limitations of this study include the observational design without a comparator control group, small sample size, and the short follow-up period.

Singh and colleagues (2016) retrospectively described the clinical experience of vedolizumab in a pediatric population with IBD at three tertiary IBD centers. A total of 52 subjects younger than 18 years of age (mean age 14.9, range 7-17 years) with Crohn’s disease (n=30; 58%) and ulcerative colitis (n=22; 42%) were prescribed vedolizumab at the discretion of the treating physician. On initiation of vedolizumab, 15 subjects were on concomitant immunomodulator therapy (6-MP, azathioprine, or methotrexate). A total of 47 of 52 (90%) subjects had failed at least one TNF antagonist agent (adalimumab, certolizumab pegol, or infliximab) and 23 of 52 (44%) had failed at least two TNF antagonist agents. Eleven subjects (21%), all with Crohn’s disease, had IBD-related operations before initiation of vedolizumab with a median time from operation to vedolizumab initiation of 10 (range 1-31) months. All subjects received vedolizumab intravenously at 0, 2, and 6 weeks and then approximately every 8 weeks. The dose of vedolizumab was 300 mg in 39 (75%) subjects and smaller subjects were dosed by weight (6 mg/kg in 11 subjects; 5 mg/kg in 2 subjects). At the time of vedolizumab initiation, 29 of 52 (56%) subjects received a corticosteroid (prednisone or oral budesonide). By week 6, 18 of 50 (36%) subjects received a corticosteroid, and by week 14, 8 of 42 (19%) subjects received prednisone (no subject was on budesonide). The primary outcome measure was clinical remission at week 14 defined as PUCAI < 10 or weighted PCDAI < 12.5. Secondary outcomes included clinical remission rates at weeks 6, 22, and 30, CRP responsiveness, and steroid-free remission.

By week 6, the median weighted PCDAI was 15 (IQR, 5.6-27.5), with 9 of 26 (35%) subjects in remission. At week 14, median weighted PCDAI was 20 (IQR, 0-35), with 10 of 24 (42%) subjects being in remission. At baseline, the median PUCAI for the 22 subjects with ulcerative colitis was 30 (IQR, 10-55) with 4 of 22 (18%) subjects in remission. By week 6, the median PUCAI was 2.5 (IQR, 0-15), with 14 of 22 (63%) subjects in remission, and week 14 median PUCAI was 0 (IQR, 0-10), with 13 of 17 (76%) subjects being in remission. At week 14, remission rates for subjects with ulcerative colitis and Crohn’s disease were 76% and 42%, respectively (p< 0.05). A total of 80% of subjects who were treatment- naive to TNF antagonist therapy experienced remission at week 14. At week 22, TNF antagonist-naive subjects had higher remission rates than TNF antagonist-exposed subjects (100% vs. 45%; p=0.04). A total of 40 (77%) subjects remained on vedolizumab at the time of last follow-up (median follow-up time, 22 weeks). Three Crohn’s disease subjects discontinued vedolizumab between weeks 22 and 30 due to lack of efficacy, and 4 ulcerative colitis subjects and 2 Crohn’s disease subjects underwent an IBD-related operation within the first 30 weeks of treatment with vedolizumab. Four of these subjects underwent colectomy and 2 subjects underwent ileocecectomy. Two subjects who underwent operation remained on vedolizumab postoperatively and were in clinical remission at the time of last follow-up. There were no infusion reactions or serious adverse events reported at last follow-up and no cases of PML or infections. Limitations of this study include the retrospective design, small sample size, heterogeneous population, and lack of a standard set of inclusion or exclusion criteria. In addition, the authors noted that lack of standardized dosing in this pediatric population led to variation of dosing, which introduces this as a potentially confounding factor.

In summary, based on the available peer-reviewed published medical literature and views of relevant medical specialists practicing in pediatrics and pediatric gastroenterology, the use of vedolizumab to induce or maintain remission may be considered a treatment option in a subset of the pediatric population 6 years of age or older with Crohn’s disease or ulcerative colitis who are refractory to treatment with conventional drug therapy or TNF antagonist agents, or in those who have failed to respond to, are intolerant of, or have demonstrated dependence on systemic corticosteroids. An industry-sponsored phase 2 clinical trial is currently recruiting participants to evaluate vedolizumab pharmacokinetics, safety and tolerability in pediatric participants (ages 2 to17 years) with moderately to severely active ulcerative colitis or Crohn's disease (NCT03138655). The estimated primary completion date for the primary outcome measure is December 2019.

Other Uses of Vedolizumab

Vedolizumab has been evaluated for use in other conditions, including graft-versus-host disease (GVHD) in individuals undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and in combination with other agents for advanced melanoma. To date, the FDA has not approved vedolizumab for the treatment of these conditions.

FDA PI Label Warnings and Precautions with Use of Vedolizumab

Vedolizumab has the following Warnings and Precautions (Entyvio PI Label, 2018):

Hypersensitivity Reactions (including anaphylaxis): Discontinue ENTYVIO if anaphylaxis or other serious allergic reactions occur. (5.1)

Infections: Treatment with 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. (5.2)

Progressive Multifocal Leukoencephalopathy: Although no cases have been observed in ENTYVIO clinical trials, JCV infection resulting in progressive multifocal leukoencephalopathy (PML) and death has occurred in patients treated with another integrin receptor antagonist. A risk of PML cannot be ruled out. Monitor patients for any new  or worsening neurological signs or symptoms. (5.3)

Definitions

5-Aminosalicylic acid (5-ASA) products: A class of anti-inflammatory drugs used to treat bowel inflammation, diarrhea, rectal bleeding, and abdominal pain in Crohn's disease and ulcerative colitis; includes mesalamine or mesalamine converting products such as balsalazide, olsalazine, and sulfasalazine.

Conventional therapy: Treatments that are widely accepted and practiced by the medical community.

Corticosteroids (systemic): A class of drugs, also referred to as glucocorticoids, which reduce inflammation and are synthetic derivatives of the natural steroid, cortisol, which is produced by the adrenal glands; includes prednisone, methylprednisone, and hydrocortisone.

Immunomodulator drugs: A class of drugs that modifies or influences the immune system.

Immunosuppressive drugs: A subclass of immunomodulator drugs that reduce inflammation by affecting the immune system; includes 6-MP, azathioprine, cyclophosphamide, cyclosporine, methotrexate, and tacrolimus; also referred to as immunosuppressant drugs.

Induction: Treatment designed as a first step toward treatment of a given condition.

Refractory disease: Illness or disease that is unresponsive to conventional treatment.

References

Peer Reviewed Publications:

  1. Chandar AK, Singh S, Murad MH, et al. Efficacy and safety of natalizumab and vedolizumab for the management of Crohn's disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2015; 21(7):1695-1708.
  2. Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017; 66(5):839-851.
  3. Conrad MA, Stein RE, Maxwell EC, et al. Vedolizumab therapy in severe pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2016; 22(10):2425-2431.
  4. Danese S, Fiorino G, Peyrin-Biroulet L, et al. Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis. Ann Intern Med. 2014; 160(10):704-711.
  5. Feagan BG, Greenberg GR, Wild G, et al. Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin. Clin Gastroenterol Hepatol. 2008; 6(12):1370-1377. Erratum in: Clin Gastroenterol Hepatol. 2009; 7(4):494.
  6. Feagan BG, Rutgeerts P, Sands BE, et al.; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013; 369(8):699-710.
  7. Hazlewood GS, Rezaie A, Borman M, et al. Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis. Gastroenterology. 2015; 148(2):344-354.
  8. Kawalec P, Mikrut A, Łopuch S. Systematic review of the effectiveness of biological therapy for active moderate to severe ulcerative colitis. J Gastroenterol Hepatol. 2014; 29(6):1159-1170.
  9. Lin L, Liu X, Wang D, Zheng C. Efficacy and safety of antiintegrin antibody for inflammatory bowel disease: a systematic review and meta-analysis. Medicine (Baltimore). 2015; 94(10):e556.
  10. Parikh A, Fox I, Leach T, et al. Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013; 19(8):1691-1699.
  11. Parikh A, Leach T, Wyant T, et al. Vedolizumab for the treatment of active ulcerative colitis: a randomized controlled phase 2 dose-ranging study. Inflamm Bowel Dis. 2012; 18(8):1470-1479.
  12. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013; 369(8):711-721.
  13. Sands BE, Feagan BG, Rutgeerts P, et al. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014; 147(3):618-627.e3.
  14. Schreiber S, Dignass A, Peyrin-Biroulet L et al. Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease. J Gastroenterol. 2018; 53(9):1048-1064.
  15. Singh N, Rabizadeh S, Jossen J, et al. Multi-center experience of vedolizumab effectiveness in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2016; 22(9):2121-2126.
  16. Singh S, Garg SK, Pardi DS, et al. Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn disease: a systematic review and network meta-analysis. Mayo Clin Proc. 2014; 89(12):1621-1635.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Gastrological Association (AGA). AGA Institute Care Pathway for the Identification, Assessment and Initial Medical Treatment in Crohn’s Disease. Available at: https://s3.amazonaws.com/aga-guidelines/pdf/ibd/Ulcerative_Colitis_Care_Pathway.pdf. Accessed on September 27, 2018.
  2. Bickston SJ, Behm BW, Tsoulis DJ, et al. Vedolizumab for induction and maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2014;(8):CD007571.
  3. Entyvio. In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated March 27, 2017. Available at: http://www.micromedexsolutions.com. Accessed on September 27, 2018.
  4. Entyvio [Product Information], Deerfield, IL. Takeda Pharmaceuticals America, Inc; February, 2018. Available at: https://general.takedapharm.com/ENTYVIOPI. Accessed on October 4, 2018.
  5. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010; 105(3):501-523. Erratum in: Am J Gastroenterol. 2010; 105(3):500.
  6. Lichtenstein GR, Hanauer SB, Sandborn WJ. Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn's disease in adults. Am J Gastroenterol. 2009; 104(2):465-483.
Index

Integrin Receptor Antagonist

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed

11/08/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. References and Discussion/General Information sections updated.

New

01/25/2018

MPTAC review. Initial document development. Removed Note from the Description section concerning CG-ADMIN-02. Moved content of DRUG.00068 Vedolizumab (Entyvio®) to new clinical utilization management guideline document with the same title.