Colectomy Rate Comparison After Treatment of Ulcerative Colitis With Placebo or Infliximab

Sandborn, William J.; Rutgeerts, Paul; Feagan, Brian G.; Reinisch, Walter; Olson, Allan; Johanns, Jewel; Lu, Jiandong; Horgan, Kevin J.; Rachmilewitz, Daniel; Hanauer, Stephen B.; Lichtenstein, Gary R.; Villiers, Willem J.S. de; Present, Daniel H.; Sands, Bruce E.; Colombel, Jean Fréd́eric

doi:10.1053/j.gastro.2009.06.061

Cited by 413 publications

(320 citation statements)

References 28 publications

(23 reference statements)

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“…Tumour necrosis factor alpha (TNF␣) is an important cytokine involved in the pathogenesis of inflammatory bowel disease and targeting this cytokine may be an effective therapy in patients with UC [3]. Infliximab, a chimeric monoclonal antibody to TNF ␣ has been shown to be effective for inducing and maintaining response and remission, inducing mucosal healing and reducing the need for colectomy in patients with moderate-to-severe UC that is refractory to conventional treatment [4][5][6][7][8][9]. However, infliximab is immunogenic and infusion reactions and loss of response related to antibodies to infliximab may be a relevant problem [10].…”

Section: Introductionmentioning

confidence: 99%

Adalimumab in active ulcerative colitis: A “real-life” observational study

Armuzzi¹,

Biancone²,

Daperno³

et al. 2013

Digestive and Liver Disease

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a b s t r a c tBackground and aims: The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods: All patients with active disease treated with adalimumab were retrospectively reviewed. Coprimary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results: Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twentytwo patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36-19.44; OR 2.63, 95% CI 2.32-14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, and with a higher rate of colectomy (HR 9.7, 95% CI 1.46-9.07). Conclusion: In this large "real-life" experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

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Section: Introductionmentioning

confidence: 99%

Adalimumab in active ulcerative colitis: A “real-life” observational study

Armuzzi¹,

Biancone²,

Daperno³

et al. 2013

Digestive and Liver Disease

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“…Su uso ha demostrado eficacia en lograr remisión libre de esteroides, curación de la mucosa y cambiar la historia natural de la enfermedad (colectomías) 15,29 . Además, en pacientes con CU moderada a severa tratados con este fármaco se ha visto un riesgo significativamente menor de colectomía a las 54 semanas de tratamiento, comparado con placebo 4 .…”

Section: Discussionunclassified

“…La EII tiende a presentar un curso crónico con períodos de remisión y actividad de duración variable, lo que hace que su tratamiento sea complejo. Los objetivos del tratamiento son lograr remisión sin esteroides, inducir y mantener la mucosa sana, remisión radiológica, mantención de la función gastrointestinal normal y prevenir cirugías, hospitalizaciones y discapacidad, todo lo cual se traduce en una mejor calidad de vida para el paciente [1][2][3][4] .…”

Section: A Enfermedad Inflamatoria Intestinal (Eii)unclassified

“…Diferentes estudios han demostrado la eficacia de la terapia con infliximab tanto en EC como en CU, logrando cumplir los objetivos del tratamiento en estas patologías 1,3,4,10,[12][13][14]15 . Infliximab está indicado en pacientes con corticodependencia, refractariedad a corticoides e inmunomoduladores, fístula perianal y manifestaciones extraintestinales asociadas a EII 9,[12][13][14]16 .…”

Section: A Enfermedad Inflamatoria Intestinal (Eii)unclassified

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Rol de infliximab en enfermedad inflamatoria intestinal: Experiencia local

et al. 2013

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“…In patients who have been diagnosed with ulcerative colitis, prophylactic total colectomy, which is associated with significant morbidity and close surveillance is currently the mainstay of approach (Ma et al, 2012;Sandborn et al, 2009;Samuel et al, 2013). Deep understanding of the mechanism of malignant transformation might enable us to develop a much better prophylactic therapy for such patients either by reversing chronic inflammation or by breaking the bridge between chronic inflammation and malignant phenotype.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic Inflammation, a Deadly Bridge to Malignant Transformation and a Fertile Soil for Cancer Prevention

Afrasiabi¹,

Edwards²,

Melekh-Shalom³

et al. 2013

OnLine Journal of Biological Sciences

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The interplay of the inflammatory microenvironment with its hypoxic niche and the potential mechanism by which they lead to malignant transformation has long been the subject of great controversy and continues to be an area of great interest today. In our previous studies we have examined this subject by using Gia2 knock out mice as the focus of our research. These mice are well known for their tendency to develop chronic inflammation in the sub mucosa of their gut, with gradual worsening and development of colon adenocarcinoma in most as they age. It has also attracted our attention that they develop a significant increase in the number of hypoxic niches in their sub mucosa, proven by EF5 staining.In contradistinction to MSI-high colon adenocarcinomas, we have also shown that histone deacetylation rather than MLH1 promoter methylation is the main mechanism of MLH1 and MSH2 deactivation in these mice. Here we show that hypoxic niches evolve under massive selective pressure of the inflammatory microenvironment as a protective shield offering survival advantage by the up regulation of NFKb and its downstream pathways, which indeed independent of true hypoxia leads to stabilization of HIF as well, securing a dual mechanism for perpetuation and expansion of hypoxic niches. We incorporated western blot and Luciferase assay of cells exposed to hypoxia+/-inflammatory cytokines to acquire data.

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Colectomy Rate Comparison After Treatment of Ulcerative Colitis With Placebo or Infliximab

Cited by 413 publications

References 28 publications

Adalimumab in active ulcerative colitis: A “real-life” observational study

Adalimumab in active ulcerative colitis: A “real-life” observational study

Rol de infliximab en enfermedad inflamatoria intestinal: Experiencia local

Hypoxic Inflammation, a Deadly Bridge to Malignant Transformation and a Fertile Soil for Cancer Prevention

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