Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohnʼs disease

Schnitzler, Fabian; Fidder, Herma H.; Ferrante, Marc; Noman, Maja; Arijs, Ingrid; Assche, Gert Van; Hoffman, Ilse; Steen, Kristel Van; Vermeire, Séverine; Rutgeerts, Paul

doi:10.1002/ibd.20927

Cited by 614 publications

(380 citation statements)

References 18 publications

Supporting

Mentioning

356

Contrasting

Unclassified

Order By: Relevance

“…As many patients with IBD were either refractory or intolerant to treat ment with the classic agents already discussed, there was an urgent need for the development of more specific novel therapeutic approaches. In this context, anti TNF agents, including infliximab, adalimumab, golimumab and certo lizumab pegol, were introduced into clin ical therapy for IBD 14,[23][24][25][26][27][28][29][30][31][32][33] . For instance, infliximab was shown to be effective for induction and maintenance of remission in both Crohn's disease and ulcerative colitis as well as for treatment of fistulas in Crohn's disease, highlighting the broad relevance of anti TNF therapy 14,24 .…”

Section: Classic Immunosuppressive Drugsmentioning

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

Section: Classic Immunosuppressive Drugsmentioning

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

“…Mucosal healing is likely to become an important therapeutic target in CD, being associated with sustained clinical remission, and reduced rates of hospitalization and surgery [46][47][48][49]. Anti-tumour necrosis factor (TNF) a agents are effective in the treatment of Crohn's disease CD because they can induce clinical remission and mucosal healing in most patients.…”

Section: Sicusmentioning

confidence: 99%

SICUS and CEUS imaging in Crohn’s disease: an update

et al. 2017

View full text Add to dashboard Cite

Endoscopy remains the main technique in the diagnosis and treatment of Crohn's disease (CD); nevertheless, the recent development of innovative and non-invasive imaging techniques has led to a new tool in the exploration of small bowel in CD patients. This paper reviews the available data on ultrasound imaging used for the evaluation of CD, highlighting the role of small intestine contrast-enhanced ultrasonography with the use of oral and intravenous contrast agents.Keywords Crohn's disease Á Contrast-enhanced ultrasound Á Small intestine contrast ultrasonography Sommario Nell'iter diagnostico e terapeutico della malattia di Crohn l'endoscopia rappresenta la principale metodica strumentale. Tuttavia, la recente introduzione di tecniche di imaging innovative e non invasive ha implementato lo studio dell'intestino nelle malattie infiammatorie croniche intestinali. La seguente revisione raccoglie i dati disponibili in letteratura relativi all'utilizzo dell'ecografia con mezzo di contrasto, sia orale (SICUS) sia endovenoso (CEUS), nella valutazione dei pazienti affetti da malattia di Crohn.

show abstract

“…The distinction between these two grades is, therefore, not clinically relevant and current postoperative therapeutic strategies are aimed at aggressively treating only severe endoscopic recurrence. Similarly, in a retrospective study on a large cohort of CD patients treated with infliximab, no difference in the long-term need of major abdominal surgery was observed in patients who achieved complete MH (absence of ulcerations) or partial MH (clear improvement of mucosal lesions, but still with ulcerations) [4]. In UC, a substudy of the ACT 1 and ACT 2 trials showed that early MH with infliximab was associated with a reduced risk of colectomy within 1 year, but the colectomy-free survival was similar in patients who achieved complete MH (Mayo score = 0) or partial MH (Mayo score = 1) [8].…”

mentioning

confidence: 89%

“…IBD encompasses a wide range of endoscopic lesions, but there is no current standardized definition of MH and several criteria have been arbitrarily used. In CD, MH has been defined either in a simple and pragmatic manner as 'absence of ulcerations at follow-up endoscopy in patients who had ulcerations at baseline' [4] or using endoscopic scores, such as the CD endoscopic index of severity or the simple endoscopic score for CD (SES-CD) [5]. Unfortunately, these scores were initially KEYWORDS: Crohn's disease • endoscopy • inflammatory bowel disease • mucosal healing • ulcerative colitis informahealthcare.comconceived as continuous-variable systems and no agreement on cut-off values to define MH exist.…”

mentioning

confidence: 99%