Polymorphisms of Tumor Necrosis Factor‐α but Not <i>MDR1</i> Influence Response to Medical Therapy in Pediatric‐Onset Inflammatory Bowel Disease

Cucchiara, Salvatore; Latiano, Anna; Palmieri, Orazio; Canani, Roberto Berni; D’Incà, R.; Guariso, Graziella; Vieni, Giuseppe; Venuto, D. De; Riegler, G.; Angelis, G.L. De; Guagnozzi, Danila; Bascietto, C.; Miele, Erasmo; Valvano, Maria Rosa; Bossa, Fabrizio; Annese, Vito

doi:10.1097/mpg.0b013e31802c41f3

Cited by 77 publications

(56 citation statements)

References 72 publications

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“…Baldassano et al 17 recently described a small cohort of 142 children with CD: 86% had involvement of the small bowel and colon (Ϯ upper GI tract). Cucchiara et al 18 showed in an Italian cohort of pediatric CD patients with Ն1 year of follow-up (n ϭ 200) that 58% had ileocolonic CD (using the Vienna classification). 18 Our data in UC are also consistent with the hypothesis that childhood-onset disease has a very high bias toward extensive disease.…”

Section: Discussionmentioning

confidence: 99%

“…Cucchiara et al 18 showed in an Italian cohort of pediatric CD patients with Ն1 year of follow-up (n ϭ 200) that 58% had ileocolonic CD (using the Vienna classification). 18 Our data in UC are also consistent with the hypothesis that childhood-onset disease has a very high bias toward extensive disease. This observation is also consistent with other datasets.…”

Section: Discussionmentioning

confidence: 99%

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Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

et al. 2008

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See Dubinsky MC et al on page 1105 in CGH;See editorial on page 1038. Background & Aims:Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease and compared them with characteristics of adult-onset disease in patients in Scotland. ; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001; OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive colitis during followup. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

et al. 2008

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“…Some studies have also tried to identify genetic factors associated with response to treatment. Polymorphisms in multi-drug resistant 1 (MDR1), TNF and migration inhibitory factor genes have been associated with corticosteroid refractoriness or sensitivity in CD and UC [45][46][47] . MDR1 polymorphism has also been associated with a higher risk of cyclosporine failure in patients with steroid-resistant UC [48] .…”

Section: Genetic Predictors Of CD Coursementioning

confidence: 99%

Clinical, serological and genetic predictors of inflammatory bowel disease course

Beaugerie¹

2012

WJG

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Patients with extensive or complicated Crohn's disease (CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines. In patients with localized and uncomplicated CD at diagnosis, early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact. In this context, there is a need for predictors of benign or unfavourable subsequent clinical course, in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions. At diagnosis, an age below 40 years, the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course. The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts. Consequently, the use of these predictors can be integrated into the elements that influence individual decisions. In the CD postoperative context, keeping smoking and history of prior resection are the strongest predictors of disease symptomatic recurrence. However, these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice. In ulcerative colitis (UC), extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease, and also with long-term colectomy and colorectal inflammation-associated colorectal cancer. In patients with extensive UC at diagnosis, a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered. At the moment, no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.

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“…However, whether this variant is itself functional or in LD with the actual causative allele is still unclear (41,42). In addition, with the exception of our pilot study in children with IBD [40] no evidence of correlation of TNF-α polymorphism with response to medical therapy has been demonstrated.…”

Section: Discussionmentioning

confidence: 50%

Polymorphisms of Tumor Necrosis Factor‐α but Not MDR1 Influence Response to Medical Therapy in Pediatric‐Onset Inflammatory Bowel Disease

Cited by 77 publications

References 72 publications

Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease

Clinical, serological and genetic predictors of inflammatory bowel disease course

A Polymorphism of the Tnf-α Gene Promotes Steroid-Resistance In patients with Inflammatory Bowel Disease

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