Effects of Vedolizumab Induction Therapy for Patients With Crohn’s Disease in Whom Tumor Necrosis Factor Antagonist Treatment Failed

Sands, Bruce E.; Feagan, Brian G.; Rutgeerts, Paul; Colombel, Jean Fréd́eric; Sandborn, William J.; Sy, Richmond; D’Haens, Geert R.; Ben‐Horin, Shomron; Xu, Jing; Rosario, Maria; Fox, Irving H.; Parikh, Asit; Milch, Catherine; Hanauer, Stephen B.

doi:10.1053/j.gastro.2014.05.008

Cited by 614 publications

(658 citation statements)

References 31 publications

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“…Among patients with CD and anti-TNF intolerance or failure, vedolizumab was not more effective than placebo in achieving clinical remission at week 6 [45]. However, an effect was shown at week 10, with 26.6% of those who received vedolizumab achieving remission, compared with 12.1% in the placebo group (p = 0.001) [45]. These data suggest that vedolizumab is effective among patients with CD refractory to conventional therapy, including anti-TNF agents, but that the onset of action is relatively slow, often requiring 10 weeks or more of therapy [45].…”

Section: Anti-integrin Inhibitors Vedolizumabmentioning

confidence: 84%

“…The primary endpoint was clinical remission at week 6 in the anti-TNF failure subgroup. Among patients with CD and anti-TNF intolerance or failure, vedolizumab was not more effective than placebo in achieving clinical remission at week 6 [45]. However, an effect was shown at week 10, with 26.6% of those who received vedolizumab achieving remission, compared with 12.1% in the placebo group (p = 0.001) [45].…”

Section: Anti-integrin Inhibitors Vedolizumabmentioning

confidence: 91%

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Emerging biologics in inflammatory bowel disease

Chan

2016

J Gastroenterol

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Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries. A number of new therapeutic targets, including novel small molecules, and cellular therapy are available or under investigation. These novel molecules include oral Janus kinase (JAK) inhibitor (tofacitinib), interleukin inhibitor (ustekinumab), oral SMAD7 antisense oligonucleotide (mongersen), and anti-integrin inhibitors (vedolizumab). Here, we review the mechanisms of action, the efficacy, and the safety data of these novel agents. Biological products that are highly similar to reference biologic products whose patents have expired-also known as ''biosimilars''-can be produced at lower cost with similar efficacy, and are also available for the treatment of IBD. We review the efficacy data for such agents as well.

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Section: Anti-integrin Inhibitors Vedolizumabmentioning

confidence: 84%

Section: Anti-integrin Inhibitors Vedolizumabmentioning

confidence: 91%

Emerging biologics in inflammatory bowel disease

Chan

2016

J Gastroenterol

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“…Two trials, GEMINI II [12] and GEMINI III [13] formed the main supporting evidence for the intervention.…”

Section: Clinical Effectiveness Evidence Submitted By the Companymentioning

confidence: 99%

“…In contrast, the GEMINI III trial [13] was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with a dosing regimen of weeks 0, 2 and 6 with assessment at weeks 6 and 10. In general, efficacy analyses in the GEMINI II and III trials [12,13] were conducted according to the intention-to-treat (ITT) principle whereby patients who withdrew prematurely were considered as treatment failures.…”

Section: Clinical Effectiveness Evidence Submitted By the Companymentioning

confidence: 99%

“…For the maintenance phase, patients from both cohorts (Cohort 1 and Cohort 2) who had a clinical response (defined as > 70 point decrease in the CDAI score) to vedolizumab at week 6 were randomised (1:1:1 ratio) to double-blind treatment with vedolizumab 300mg i.v. During the 10 week induction phase of the GEMINI III trial [13], 416 individuals were enrolled. 315 individuals had a previous inadequate response to, loss of response to, or intolerance of one or more anti-TNFs and 101 individuals were naïve to an anti-TNF-.…”

Section: Clinical Effectiveness Evidence Submitted By the Companymentioning

confidence: 99%

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Vedolizumab for Treating Moderately to Severely Active Crohn’s Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

et al. 2016

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As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost-effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active Crohn's disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence for the clinical effectiveness and cost-effectiveness of the technology, based upon the company's submission to NICE.The GEMINI II and GEMINI III trials formed the main supporting evidence for the intervention. Both studies were Phase III, multicentre, randomised, double-blind, placebo-controlled trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naïve to tumour necrosis factor-alpha antagonist (anti-TNF-), and patients who had an inadequate response to, loss of response to, or intolerance to immunomodulators or anti-TNF-. The GEMINI II trial was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2 with assessment at week 6) and maintenance treatment (weeks 6 to 52). In contrast, the GEMINI III trial was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only with doses at weeks 0, 2 and 6 with assessment at weeks 6 and 10.In the absence of any direct head-to-head randomised controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate to severe Crohn's disease, the company conducted a network meta-analysis (NMA) which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of: clinical response, enhanced clinical response, clinical remission, and discontinuation due to adverse events.The company model estimated the incremental cost-effectiveness ratio (ICER) for vedolizumab compared with standard of care (consisting of 5-aminosalicylic acid [5-ASAs], corticosteroids and immunosuppressants) to be £21,620 per QALY gained within the anti-TNF-failure population (which included a confidential Patient Access Scheme for vedolizumab). The ICERs were above £30,000 per QALY gained for the mixed intention to treat (ITT) population (including both anti-TNF-naïve and failure population) and in patients who were anti-TNF-naïve only. The ERG identified a number of limitations which were believed to limit the robustness of the results presented by the company. These limitations could not be addressed by the ERG without major restructuring of the economic model. Therefore, the ERG concluded that results from the company's model needed to be interpreted with caution and that it was unclear whether the ICERs would increase or decrease following amendment of the identified structural issues. 3 Key Points for Decision Makers Vedolizumab appears to be more effective in both the inductio...

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