Vedolizumab for induction and maintenance of remission in ulcerative colitis

Bickston, Stephen J.; Behm, Brian W.; Tsoulis, David J; Cheng, Jianfeng; MacDonald, John K; Khanna, Reena; Feagan, Brian G.

doi:10.1002/14651858.cd007571.pub2

Cited by 53 publications

(38 citation statements)

References 40 publications

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“…These infections were prob ably related to natalizumab induced blockade of T cell homing to the brain via α4β1 integrins, suggesting that a more specific blockade of α4β7 integrins was important. Subsequently, the α4β7 integrin specific antibody vedolizumab was developed and showed efficacy in clinical phase III trials for remission induction and maintenance in Crohn's disease and ulcerative colitis [58][59][60][61][62][63] .…”

Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

512

403

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Inflammatory bowel diseases (including IBD, exempli fied by Crohn's disease and ulcerative colitis) are chronic relapsing disorders affecting the gastrointestinal tract. IBD has a progressive and destructive nature and, there fore, can cause various complications including steno ses, abscesses, fistulas, extraintestinal manifestations and colitis associated neoplasias and cancer 1,2 . Thus, effective therapeutic approaches are of high clinical rele vance in patients with IBD. This Review summarizes current therapeutic strategies and highlights emerging new treatment approaches for IBD with special refer ence to the proposed molecular mechanisms of action of anti inflammatory drugs. Current IBD therapiesClassic anti-inflammatory drugs. 5 Aminosalicylates (5 ASAs) are important anti inflammatory drugs that are frequently used for anti inflammatory therapy in patients with ulcerative colitis 3 . By contrast, 5 ASA based drugs show little or no efficacy in inducing res olution of clinical symptoms and tissue inflammation in patients with Crohn's disease 4 .5 ASAs are effective for induction and mainten ance of remission in ulcerative colitis and might also reduce the risk of developing colitis associated tumours in these patients 5 . Several mechanisms of action for 5 ASAs have been proposed, including reduction of prostaglandin synthesis via inhibition of cyclooxygenase, suppression of proinflammatory cytokine production and oxygen free radicals, inhib ition of lipoxygenase, blockade of neutrophil chemo taxis and mast cell activation, and impairment of nuclear factor κB activation (NF κB) in immune cells 3 . Moreover, studies in mice revealed that 5 ASA based drugs augment peroxisome proliferator activated receptor γ (PPARγ) expression and promote PPARγ translocation from the cytoplasm to the nucleus where they result in activation of peroxisome proliferator hormone response element driven genes to suppress colitis activity 6,7 .In addition to 5 ASAs, corticosteroids (systemically or topically delivered) have been used for remission induction in ulcerative colitis 2 . Although cortico steroids favour induction of remission in both ulcer ative colitis and Crohn's disease, they are not suitable for mainten ance of remission in IBD 1,2 . Mechanistically, gluco corticoids bind to a specific cytosolic receptor fol lowed by translocation of the complex to the nucleus to either activate or repress gene transcription (via bind ing to DNA corticosteroid response elements) 8,9 . Additionally, the glucocorticoid-receptor complex can inactivate pro inflammatory transcription factors such as NF κB and activator protein 1 (AP1) via proteinprotein inter actions, thereby preventing their activation of inflammatory mediators (for example, leukotrienes and cytokines such as IL 1 and IL 6). REVIEWS© 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

512

403

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“…This systematic review and meta-analysis, which is based on a previously published Cochrane review, 15 summarizes current evidence regarding the use of vedolizumab as an induction and maintenance agent for UC.…”

mentioning

confidence: 99%

Vedolizumab for Induction and Maintenance of Remission in Ulcerative Colitis

Mosli

MacDonald

Bickston³

et al. 2015

Inflammatory Bowel Diseases

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“…A recent Cochrane review including four studies with a low risk of bias showed that vedolizumab was superior to placebo for induction of clinical remission and response and endoscopic remission in patients with moderate to severe active UC, and for the prevention of relapse in patients with quiescent UC [43].…”

Section: Anti-integrin Inhibitors Vedolizumabmentioning

confidence: 99%

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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Vedolizumab for induction and maintenance of remission in ulcerative colitis

Cited by 53 publications

References 40 publications

Current and emerging therapeutic targets for IBD

Current and emerging therapeutic targets for IBD

Vedolizumab for Induction and Maintenance of Remission in Ulcerative Colitis

Emerging biologics in inflammatory bowel disease

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