Aminosalicylates for induction of remission or response in Crohn's disease

Lim, Weeâ€Chian; Wang, Yongjun; MacDonald, John K; Hanauer, Stephen B.

doi:10.1002/14651858.cd008870.pub2

Cited by 156 publications

(125 citation statements)

References 103 publications

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“…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 .…”

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confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

507

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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confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

507

403

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“…22 However a recent metaanalysis has reaffirmed that 5-ASA has little benefit for the treatment of active CD. 20 In concordance with this evidence the actual treatment guideline for pediatric CD recommends oral 5-ASA only for selected patients with a very mild colonic disease. 1 Only 13% of CD patients in our cohort had colonic-only disease at diagnosis, whereas nearly half of all CD patients received oral 5-ASA at some time point.…”

Section: -Asa In CDmentioning

confidence: 83%

“…20 Furthermore nearly half of the CD patients in our cohort were treated with oral 5-ASA during their disease course. Earlier pediatric studies which suggested a possible benefit of 5-ASA in the treatment of small intestinal CD 21 may have influenced these prescribing practices.…”

Section: -Asa In CDmentioning

confidence: 99%

The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease

Sokollik

Fournier

Rizzuti

et al. 2018

Journal of Clinical Gastroenterology

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Background: In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn’s disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease. Materials and Methods: Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed. Results: Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%. Conclusions: In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy.

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“…High-dose mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02; 95 % CI 0.75 to 5.45) or response (n=615). At the same time, no statistically significant difference was found between high-dose mesalamine and conventional corticosteroids (RR 1.04; 95 % CI 0.79 to 1.36; n=178) [67]. Another meta-analysis came up with slightly different conclusions.…”

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confidence: 91%

Indian Society of Gastroenterology consensus statements on Crohn’s disease in India

Ramakrishna

Makharia

Ahuja

et al. 2015

Indian J Gastroenterol

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In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on Crohn's disease (CD). This consensus, produced through a modified Delphi process, reflects our current recommendations for the diagnosis and management of CD in India. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.

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Aminosalicylates for induction of remission or response in Crohn's disease

Cited by 156 publications

References 103 publications

Current and emerging therapeutic targets for IBD

Current and emerging therapeutic targets for IBD

The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease

Indian Society of Gastroenterology consensus statements on Crohn’s disease in India

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