다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

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Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management

,2,3Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, GermanyDivision of Gastroenterology, Department of Medicine, MtSinai Hospital and University Health Network;University of Toronto, 600 University Avenue, Toronto, ON, Canada M5G 1X5 and University of Leuven, BelgiumReceived 26 August 2012; accepted 3 September 2012KEYWORDS

Second European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Current management

https://www.gastrojournal.org/article/S0016-5085(13)00846-9/pdf

Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.

Recent studies have identified mucosal healing on endoscopy as a key prognostic parameter in the management of inflammatory bowel diseases (IBD), thus highlighting the role of endoscopy for monitoring of disease activity in IBD. In fact, mucosal healing has emerged as a key treatment goal in IBD that predicts sustained clinical remission and resection-free survival of patients. The structural basis of mucosal healing is an intact barrier function of the gut epithelium that prevents translocation of commensal bacteria into the mucosa and submucosa with subsequent immune cell activation. Thus, mucosal healing should be considered as an initial event in the suppression of inflammation of deeper layers of the bowel wall, rather than as a sign of complete healing of gut inflammation. In this systematic review, the clinical studies on mucosal healing are summarised and the effects of anti-inflammatory or immunosuppressive drugs such as 5-aminosalicylates, corticosteroids, azathioprine, ciclosporin and anti-TNF antibodies (adalimumab, certolizumab pegol, infliximab) on mucosal healing are discussed. Finally, the implications of mucosal healing for subsequent clinical management in patients with IBD are highlighted.

/pdf/mucosal-healing-in-inflammatory-bowel-diseases-a-systematic-29o7mjwkc5.pdf

Mucosal healing in inflammatory bowel diseases: a systematic review

Background Tumour necrosis factor alpha (TNFα)-antagonism effectively treats ulcerative colitis (UC). The golimumab clinical programme evaluated subcutaneous (SC) and intravenous (IV) induction, and SC maintenance regimens, in TNFα-antagonist-naive patients with moderate-to-severe active UC despite conventional treatment. Aim To evaluate dose-response relationship, select IV golimumab induction doses for continued development, and evaluate the safety and efficacy of selected doses. Methods Adults with Mayo scores of 6-12 and endoscopic subscores ≥2 were enrolled into this multicentre, randomised, double-blind, placebo-controlled, integrated Phase 2/3 dose-finding/dose-confirming study. In Phase 2, 176 patients were randomised (1:1:1:1) to a single IV infusion of placebo, 1-, 2- or 4-mg/kg golimumab. While Phase 2 data were analysed to select doses for continued development, 71 additional patients were randomised. Phase 3 enrolment stopped after 44 additional patients were randomised (1:1:1) to placebo, 2- or 4-mg/kg golimumab. Due to insufficient power for the Phase 3 primary endpoint analysis (clinical response at week 6), efficacy analyses are considered exploratory and include all randomised patients. Results No dose-response was observed in Phase 2; however, higher serum golimumab exposure was associated with greater proportions of patients achieving more favourable clinical outcomes, clinical response and greater improvement in Mayo scores compared with placebo-treated patients and those with lower serum concentrations. Among all randomised patients, numerically greater proportions were in clinical response at week 6 in the 2- and 4-mg/kg golimumab groups compared with placebo [44.0% (33/75) and 41.6% (32/77) vs. 30.1% (22/73)]. Conclusions Efficacy with single-dose golimumab IV induction was lower than expected and less than observed in the SC induction study. No new safety findings were observed. ClinicalTrials.gov Number, NCT00488774.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.13291

Randomised clinical trial: a placebo-controlled study of intravenous golimumab induction therapy for ulcerative colitis

943d A Phase 2/3 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Subcutaneous Golimumab Induction Therapy in Patients with Moderately to Severely Active Ulcerative Colitis: PURSUIT SC

Purpose The etiology of Inflammatory Bowel Disease (IBD) remains currently unknown but evidence would suggest that it results from a complex interplay between genetic susceptibility genes, the intestinal microbiome and the environment, resulting in an increased response towards microbial and self-antigens, followed by the development of pre-clinical intestinal inflammation as a precursor to overt clinical disease. Efforts are needed to provide insights into the characterization of the disease, the possible prediction of complications, and the detection of a pre-clinical disease state where, through early screening and intervention, disease course can be reversed, attenuated or even prevented. A consortium of academic, industry and governmental organization investigators initiated this study to enable an assessment of pre-disease biomarkers in patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC). Participants A retrospective cohort of 1000 UC and 1000 CD cases with 500 matched controls was drawn from an active duty US military personnel population with relevant inclusion criteria with three associated pre-disease and a single disease-associated archived serum samples. Findings to date The PREDICTS study has been established as a biorepository platform study to perform novel discovery and analysis efforts in the field of IBD and proteomic systems biology. Future plans This study is poised to enable the assessment of novel biomarkers within the serum compartment to be analyzed with the goal of identifying pre-disease signals that ultimately predict disease risk, and further elucidate disease pathogenesis in the early stages of the disease process, and identify novel exposures that increase disease risk.

Cohort profile of the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study: Rationale, organization, design, and baseline characteristics

R. Strauss

Papers

Randomised clinical trial: a placebo-controlled study of intravenous golimumab induction therapy for ulcerative colitis

943d A Phase 2/3 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Subcutaneous Golimumab Induction Therapy in Patients with Moderately to Severely Active Ulcerative Colitis: PURSUIT SC

Cohort profile of the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study: Rationale, organization, design, and baseline characteristics

Sa1935 Population Pharmacokinetic Modeling Analysis of Golimumab in Adult Patients With Moderately to Severely Active Ulcerative Colitis

Mo1794 Delayed Response to Golimumab Therapy: UC Patient Characteristics and Long-term Clinical Outcome: Post-Hoc Analyses from the PURSUIT Program