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Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease

World Journal of Gastroenterology 2019年第31期25卷 4481-4492页

作者： Peter Hoffmann Johannes Krisam Cyrill Wehling petra kloeters-plachky Yvonne Leopold Nina Belling Annika Gauss Department of Gastroenterology and Hepatology University Hospital HeidelbergHeidelberg 69120Germany Department of Medical Biometry University Hospital HeidelbergHeidelberg 69120Germany

BACKGROUND Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease(CD)in 2016,and there is an urgent need for data on its everyday *** To obtain data on the daily use of *** This is a retrospective monocentric *** with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient *** primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24±6 wk of ustekinumab *** study endpoints were:achievement of mucosal healing,sonographic and magnetic resonance imaging response,biochemical response,the need for intestinal surgery within 24±6 wk after treatment initiation,the occurrence of adverse events,treatment discontinuation due to nonresponse or adverse events,improvement of extraintestinal manifestations,clinical response at 48±6 wk of therapy,and association of response with nucleotid oligodimerisation domain 2 *** Fifty-seven patients with CD(5.3%anti-tumour necrosis factorαnaive,63.2%having undergone at least one intestinal surgery)were included in the *** patients(35.1%)achieved steroid-free clinical remission,6(10.5%)steroid-free clinical response and 31(54.4%)were *** discontinuation due to adverse events occurred in two patients(3.5%).Male sex,the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab *** In a“real-world”treatment-refractory cohort of patients with CD,ustekinumab appeared efficacious and safe.

关键词： Eeal-world Ustekinumab Crohn’s disease

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Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing cholangitis

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World Journal of Gastroenterology 2013年第33期19卷 5454-5463页

作者： Annika Gauss Robert Ehehalt Wolf-Dieter Lehmann Gerhard Erben Karl-Heinz Weiss Yvonne Schaefer petra kloeters-plachky Adolf Stiehl Wolfgang Stremmel Peter Sauer Daniel Nils Gotthardt Gastroenterology and Hepatology Unit Department of Internal MedicineUniversity Hospital Heidelberg Department of Spectroscopy German Cancer Research Center

AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were *** of these patients were diagnosed with PSC,10 with SSC,11 with choledocholithiasis or no identifiable biliary disease,and 6 with cholangiocellular carcinoma(CCC).Bile acid,cholesterol,protein,and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical ***(PC)and lysophosphatidylcholine(LPC)species were quantified using nanoelectrospray ionization tandem mass ***:Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition,with only minor statistical *** biliary PC concentrations were highest in controls(8030±1843 mol/L)and lowest in patients with CCC(1969±981 mol/L)(P=0.005,controls vs SSC and CCC,respectively,P<0.05).LPC contents in bile were overall low(4.2%±1.8%).Biliary LPC/PC ratios and ratios of biliary PC to bilirubin,PC to cholesterol,PC to protein,and PC to bile acids showed no intergroup ***:PC and LPC profiles being similar in patients with or without sclerosing cholangitis,these phospholipids are likely not of major pathogenetic importance in this disease group.

关键词： Primary sclerosing cholangitis Secondary sclerosing cholangitis Cholangiocellular carcinoma Phosphatidylcholine Lysophosphatidylcholine Bile Mass spectrometry

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原发性硬化性胆管炎中高剂量熊去氧胆酸对其在胆汁中的富集的影响

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世界核心医学期刊文摘（胃肠病学分册） 2005年第2期1卷 41-42页

作者： Rost D. Rudolph G. kloeters-plachky P. Stiehl A. 樊菁 Medizinische Universittsklinik Bergheimer Str. 58 D-69115 Heidelberg GermanyDr.

Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseas es. Inprimary sclerosing cholangitis (PSC), there is evidence that high doses ( ±20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how highdose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We det ermined the biliary bile acid composition in 56 patients with PSC including 30 p atients with repeat bile samples treated with various doses of UDCA. At a UDCA d ose of 10-13 mg/kg/d (n = 18) biliary UDCA represented 43.1%+0.3%(mean +SD) of total bile acids; at a UDCA dose of 14-17 mg/kg (n = 14), its biliary conte nt increased to 46.9%+0.3%, at 18-21 mg/kg (n = 34) to 55.9%+0.2%, at 22 -25 mg/kg (n = 12) to 58.6%+2.3%, and at 26-32 mg/kg (n = 8) to 57.7%+0.4 %. During UDCA treatment, the biliary content of all other bile acids was uncha nged or decreased. In conclusion, biliary enrichment of UDCA increases with incr easing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxi c hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses.

关键词：熊去氧胆酸 UDCA 胆汁淤积性肝病胆汁样细菌降解平台期

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