Crohn's disease

Baumgart, Daniel C.; Sandborn, William J.

doi:10.1016/s0140-6736(12)60026-9

Cited by 1,842 publications

(1,416 citation statements)

References 137 publications

Supporting

Mentioning

1,359

Contrasting

Unclassified

Order By: Relevance

“…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 .…”

mentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

528

403

View full text Add to dashboard Cite

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 .

show abstract

mentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

528

403

View full text Add to dashboard Cite

show abstract

“…[1][2][3] Progressive inflammation and surgery result in digestive tract damage that manifests with strictures, short bowel syndrome and stoma formation and is associated with refractory non-inflammatory gastrointestinal symptoms. 1,4 Although appropriate use of conventional and biologic therapies can induce mucosal healing, a significant number of patients experience primary or secondary non-response. 1,5 Patients with treatment refractory CD are prepared to undergo a significant treatment related risk to achieve remission.…”

Section: Introductionmentioning

confidence: 99%

“…1,4 Although appropriate use of conventional and biologic therapies can induce mucosal healing, a significant number of patients experience primary or secondary non-response. 1,5 Patients with treatment refractory CD are prepared to undergo a significant treatment related risk to achieve remission. 6 There has been considerable interest in case reports that autologous haematopoietic stem cell transplantation (HSCT) can induce sustained disease remission in such patients.…”

Section: Introductionmentioning

confidence: 99%

Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial

Lindsay

Allez

Clark

et al. 2017

The Lancet Gastroenterology & Hepatology

View full text Add to dashboard Cite

BACKGROUND The randomised controlled ASTIC trial showed no benefit of mobilisation and autologous haematopoietic stem-cell transplantation (HSCT) compared with mobilisation followed by conventional therapy using a stringent primary endpoint (steroid-free clinical remission for 3 months with no endoscopic or radiological evidence of intestinal inflammation) in patients with treatment-refractory Crohn's disease. We now assess HSCT in patients enrolled in the ASTIC trial using endpoints that are traditional for clinical trials in Crohn's disease, and identify factors that predict benefit or harm. METHODS Patients who underwent mobilisation and were randomly assigned to conventional therapy in the ASTIC trial were offered HSCT at 1 year and underwent complete assessment for a further year. We report analyses of the combined cohort of patients who underwent HSCT at any time during the ASTIC trial programme. The primary outcome for this analysis was 3-month steroid-free clinical remission at 1 year after HSCT (Crohn's Disease Activity Index [CDAI] <150). We also examined the degree of endoscopic healing at 1 year. Multivariate analysis was performed to identify factors associated with achieving the primary endpoint by using logistic regression, and factors associated with experiencing a serious adverse event using Poisson regression. Participants were not masked to treatment, but the adjudication panel that reviewed radiology and endoscopy was masked to allocation and visits. All patients who underwent HSCT and had data available at baseline and 1-year follow-up were included in the primary and safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00297193. FINDINGS Between June 28, 2007, and Sept 1, 2011, 45 patients were enrolled in the ASTIC trial from 11 European transplant units. 23 patients were randomly assigned to immediate HSCT, and 22 patients were assigned to mobilisation followed by conventional care. After completion of the ASTIC trial, 17 patients from the conventional care group received HSCT. In the combined cohort, data were available for 40 patients at baseline and 38 patients at 1 year after HSCT (one patient died, one withdrew). At 1 year after HSCT, 3-month steroid-free clinical remission was seen in 13 (38%, 95% CI 22-55) of 34 patients with available data for the whole year. Complete endoscopic healting was noted in 19 (50%, 34-66) of 38 patients. On multivariate analyses, factors associated with the primary outcome were short disease duration (odds ratio [OR] 0·64, 95% CI 0·41-0·997 per year; p=0·048) and low baseline CDAI (0·82, 0·74-0·98 per 10 units; p=0·031). 76 serious adverse events occurred in 23 of 40 patients with available data. The most common serious adverse event was infection, most of which were treatment related. Smoking and perianal disease at baseline were independent factors associated with the number of serious adverse events (OR 3·07 [95% CI 1·75-5·38; p=0·0001] for smoking and 3·97 [2·17-7·25; p<0·0001] for perianal disease) on multivariate...

show abstract

“…La maladie de Crohn, maladie inflammatoire chronique de l'intestin, constitue une bonne illustration de ce problème [11]. La composante génétique de cette maladie, qui présente une récurrence familiale importante, ainsi brièvement les études GWAS dans leur contexte scientifique.…”

Section: L'exemple De La Maladie De Crohnunclassified

Génomique, de la recherche à la clinique

Bourgain

2014

Med Sci (Paris)

View full text Add to dashboard Cite

> Alors que la génomique est parfois présentée comme un domaine de recherche dont les résul-tats passent rapidement dans les pratiques cliniques, la réalité est plus contrastée. Pour illustrer certaines des difficultés rencontrées, cet article s'intéresse aux applications des résultats obtenus par les études d'association sur tout le génome (GWAS, genome-wide association studies). Après avoir brièvement replacé les GWAS dans leur contexte scientifique, nous illustrons ces études par deux exemples emblématiques. Le cas de la maladie de Crohn permet de souligner les limites des résultats des GWAS en matière de prédiction individuelle de risque. Le cas de la warfarine met en lumière les difficultés à démontrer l'utilité clinique d'un recours aux données génétiques dans les décisions théra-peutiques. L'article insiste sur la simplification des modèles causatifs de maladie sous-tendant la méthodologie des GWAS. Fécond pour une démarche exploratoire de recherche, ce réduc-tionnisme, confronté à son utilisation clinique, montre ses limites.

show abstract

Crohn's disease

Cited by 1,842 publications

References 137 publications

Current and emerging therapeutic targets for IBD

Current and emerging therapeutic targets for IBD

Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial

Génomique, de la recherche à la clinique

Contact Info

Product

Resources

About