Bruining, David H.

SummaryBackgroundReliable tools for patient selection are critical for clinical drug trials.AimTo evaluate a consensus‐based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials.MethodsThis study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150–220 (n = 4); 220–450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14‐day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES‐CD).Results37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test–retest and inter‐reader reliability scores. The MaRIA scores for the terminal ileum had excellent test–retest and inter‐reader reliability, with correlations >0.9. The proximal ileum showed strong within‐reader agreement (0.90–0.96), and fair between‐reader agreement (0.59–0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES‐CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra‐abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%.ConclusionsMagnetic resonance enterography of high‐quality and reproducibility was feasible in a global multi‐ centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.

SummaryBackgroundCertolizumab pegol (CZP) is Food and Drug Administration (FDA)‐approved to treat Crohn's disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established.AimTo report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6‐year period since FDA‐approval at a tertiary care centre.MethodsAll CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record‐based review of steroid‐free complete response (SCR), loss of response and safety.ResultsA total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9–24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5–59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75–12.61). Negative predictors included present perianal fistula (HR, 0.39; 95% CI, 0.16–0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04–0.76). Twenty‐three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events.ConclusionsCertolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics‐exposed patients. It may be more effective in patients without early‐aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula.

AbstractBackground and AimHamartomatous polyposis syndromes (HPS) are a group of rare inherited autosomal dominant disorders. Small bowel polyposis is one of the manifestations of HPS. Double‐balloon enteroscopy (DBE) with polypectomy may obviate repeated small bowel surgeries for polyp intussusception, obstruction, or bleeding. The efficacy and safety of DBE‐assisted polypectomy in HPS patients with clinically significant small bowel polyposis were evaluated.MethodsAll HPS patients who underwent DBE from January 2007 to April 2011 were identified using a prospectively maintained database. Data on patient demographics, pre‐DBE radiological studies, polyp characteristics, procedural outcomes, and complications were abstracted.ResultsTwenty‐two patients underwent a total of 34 DBE procedures. Pre‐DBE imaging included computed tomography enterography (n = 15), computed tomography enteroclysis (n = 5), small bowel follow‐through (n = 1), and magnetic resonance enterography (n = 1). Any small bowel polyp ≥ 1 cm in size on radiological imaging was referred for DBE‐assisted polypectomy. Antegrade and retrograde DBE were successful in reaching and resecting targeted polyps in 90% (18/20) and 71.4% (10/14) of procedures, respectively. The overall success rate for DBE‐assisted polypectomy was 82.3% (95% confidence interval: 66.5–91.6%). The median size of resected polyps was 2 cm (range 1–5 cm) and all were hamartomas. Minor adverse events occurred in four (11.8%) procedures, including abdominal pain (n = 2), immediate post‐polypectomy bleeding (n = 1), and self‐limited hematochezia (n = 1).ConclusionsDBE‐assisted polypectomy was successful in over 80% of HPS patients with an acceptable margin of safety. To the knowledge of the authors, this is one of the largest single‐center studies to report on the performance and safety of DBE‐assisted polypectomy in HPS patients.

SummaryBackgroundUlcerative colitis (UC) and Crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (OLT) despite post‐transplantation immunosuppressive therapy.AimTo evaluate the efficacy and safety of anti‐tumour necrosis factor (anti‐TNF) agents for the management of IBD following OLT.MethodsWe reviewed the records of patients with a diagnosis of IBD who underwent OLT at Mayo Clinic Rochester between 1985 and 2009. Patients were included if they had received anti‐TNF therapy post‐OLT. Clinical response was defined as a physician's assessment of improvement after 12 weeks of anti‐TNF usage, and mucosal healing was defined as the absence of ulcerations on follow‐up endoscopy.ResultsThe median age of the eight study patients was 42.0 years and 37.5% were female patients. All had been diagnosed with IBD prior to OLT (UC in three and Crohn's disease in five). Indication for OLT was cirrhotic stage primary sclerosing cholangitis (PSC), and three concomitantly had cholangiocarcinoma. Clinical response was demonstrated in seven of eight patients (87.5%) and mucosal healing was demonstrated in three of seven (42.9%). Four infections (oral candidiasis, Clostridium difficile colitis, bacterial pneumonia and cryptosporidiosis) in three patients were reported. One patient developed an Epstein–Barr virus‐positive post‐transplant lympho‐proliferative disorder. One death occurred due to complications from recurrent PSC.ConclusionsStarting Anti‐TNF therapy following orthotopic liver transplantation appears to be a potential option for inflammatory bowel disease management. Additional studies are needed, however, to confirm these findings and to further assess risks associated with this treatment strategy.