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Dual biologic therapy with ocrelizumab for multiple sclerosis and vedolizumab for Crohn's disease:A case report and review of literature

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world Journal of Clinical Cases 2022年第8期10卷 2569-2576页

作者： Michael Au Nikola Mitrev rupert w leong Viraj Kariyawasam Department of Gastroenterology and Hepatology Blacktown and Mt Druitt HospitalsWestern Sydney Local Health DistrictSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversityBlacktown 2148New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustralia Endoscopy Department and Inflammatory Bowel Disease Service Concord HospitalSydney 2137New South WalesAustralia Concord Clinical School University of SydneySydney 2137New South WalesAustralia Inflammatory Bowel Disease Service Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustria

BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated *** had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with *** CD diagnosis was confirmed radiologically,endoscopically,histologically,and *** patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on *** adverse reactions were observed for the duration of *** safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was *** DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated *** biologics,which have improved safety profiles and gut specificity,may provide promising avenues for ***,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy *** evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary *** research from controlled trials is needed to better understand the safety profile of DBT in *** immunopathological mechanisms underlying DBT also remain to be clarified.

关键词： Dual biologic therapy Combination Immunosuppression Safety Autoimmune Case report

Faecal microbiota transplantation as an elixir of youth

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 488-489页

作者： Craig Haifer Sudarshan Paramsothy rupert w.leong Concord Clinical School The University of SydneySydneyAustralia Gastroenterology and Liver Services Concord Repatriation General HospitalSydneyAustralia South western Clinical School UNSWSydneyAustralia

The intestinal microbiota has been increasingly seen to be responsible for various gastrointestinal disorders such as inflammatory bowel diseases(1).However,their effects on systemic physiological processes unrelated ... 详细信息

关键词： diseases gastrointestinal unrelated

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEwS pharmacokinetics study

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world Journal of Gastroenterology 2025年第2期31卷 102-112页

作者： Thanaboon Chaemsupaphan Aviv Pudipeddi Hui-Yu Lin Sudarshan Paramsothy Viraj C Kariyawasam Melissa Kermeen rupert w leong Department of Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139New South WalesAustralia Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Faculty of Medicine and Health University of SydneySydney 2139New South WalesAustralia Department of Gastroenterology Tan Tock Seng HospitalSingapore 308433Singapore Faculty of Medicine and Health Sciences Macquarie UniversitySydney 2139New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversitySydney 2148New South WalesAustralia

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and *** is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is *** To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance *** This is a post-hoc analysis of prospective randomized clinical trial(VIEwS)involving UC patients across 8 centers in Australia from 2018 to *** in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving *** evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine *** There were 62 UC participants with mean age of 43.4 years and 42%were *** participants received vedolizumab as maintenance therapy with 67.7%withdrew *** serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies ***-tients with clinical remission had higher trough concentrations at week *** quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving *** A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be *** thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remi

关键词： Pharmacokinetic Vedolizumab Thiopurine Ulcerative colitis Trough concentration Antibody Inflammatory bowel diseases

Epidemiology of inflammatory bowel disease in South America: A systematic review

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world Journal of Gastroenterology 2019年第47期25卷 6866-6875页

作者： Sriharan Selvaratnam Santiago Gullino Lisa Shim Eric Lee Alice Lee Sudarshan Paramsothy rupert w leong Department of Gastroenterology and Hepatology Macquarie University Hospital

BACKGROUND The worldwide epidemiology of inflammatory bowel disease(IBD)is rapidly *** Crohn’s disease(CD)and ulcerative colitis(UC)incidence and prevalence have been recorded in developing regions such as Asia,Africa and Eastern Europe where it was previously thought to be *** this is also the case in South America is not well *** that developing regions worldwide have increasing IBD incidence would indicate that environmental change plays a significant role in the development of *** To report the incidence,prevalence and disease characteristics of CD and UC within the South American *** A systematic review was conducted by searching published studies in major international and regional databases(MEDLINE,EMBASE and Scopus)between January 1990 and December *** considered were incidence,prevalence,phenotype,environmental and genetic factors,ethnicity and gender.A pair of independent reviewers screened and reviewed all identified *** One hundred and sixty two citations were initially retrieved with 18 studies included in this systematic *** majority of included studies were from Brazil(n=13,72%).The incidence of UC ranged from 4.3-5.3/100000 personyears whilst the incidence of CD ranged from 0.74-3.5/100000 *** ranged from 15.0-24.1/100000 inhabitants for UC and from 2.4-14.1/100000 inhabitants for *** incidence and prevalence of both UC and CD has increased significantly in Brazil over the past 21 *** was the most common disease distribution in patients with UC whilst colonic involvement was the most common distribution in *** residing in urban areas were at higher risk of developing both CD and *** The IBD burden in South America is increasing at a rate possibly even greater than other developing regions around the *** is a paucity of highquality epidemiological studies and further robust and representative data are

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis South America Epidemiology

Knowledge and attitudes towards the use of histological assessments in ulcerative colitis by gastroenterologists vs pathologists

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world Journal of Gastroenterology 2023年第2期29卷 378-389页

作者： Aviv Pudipeddi Caroline Fung Britt Christensen Robert V Bryant Kavitha Subramaniam John Chetwood Sudarshan Paramsothy rupert w leong Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139Australia Faculty of Medicine and Health Concord Clinical SchoolUniversity of SydneySydney 2138Australia Department of Anatomical Pathology Concord Repatriation General HospitalSydney 2139Australia Department of Gastroenterology Royal Melbourne HospitalMelbourne 3050Australia Department of Medicine University of MelbourneMelbourne 3052Australia Department of Gastroenterology and Hepatology The Queen Elizabeth HospitalAdelaide 5011Australia Gastroenterology and Hepatology Unit Canberra HospitalCanberra 2605Australia Australian National University Medical School Australian National UniversityCanberra 2601Australia Faculty of Medicine and Health Sciences Macquarie University HospitalSydney 2109Australia

BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis(UC).However,the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is *** To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and *** A prospective,cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was *** survey consisted of 34 questions to assess gastroenterologists’and pathologists’knowledge(score out of 19)and attitudes towards histological assessment in *** questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting *** included knowledge of histological assessment of disease activity and dysplasia,knowledge of histological scoring systems for ulcerative colitis,uptake of histology scoring systems in routine practice,attitudes towards the role of histological activity,and the use of histological activity in clinical *** Of 89 responders(77 gastroenterologists,12 pathologists),there was almost universal acceptance that histological assessment should form part of UC evaluation[95%gastroenterologists,92%pathologists].However,gastroenterologists reported that 92%of their pathologists do not use a histological scoring *** of a formal histological scoring system was preferred by 77%of gastroenterologists and 58%of *** groups lacked awareness of the Geboes Score,Nancy Index and Robarts Histopathological Index scoring systems with 91%,87%,and 92%of gastroenterologists respectively;and 83%,83%,and 92%pathologists respectively,being uncertain of scoring systems’remission *** knowledge score was not significantly different between gastroenterologist

关键词： Histology Scoring system Ulcerative colitis Survey

Epstein Barr virus-positive mucocutaneous ulcer of thecolon associated Hodgkin lymphoma in Crohn＇s disease

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world Journal of Gastroenterology 2015年第19期21卷 6072-6076页

作者： Neil R Moran Bradley webster Kenneth M Lee Judith Trotman YiuLam Kwan John Napoli rupert w leong Neil R Moran Rupert gW Leong Gastroenterology and Liver Services Concord Repatriation General Hospital Sydney NSW 2137 Australia.

Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.

关键词： Epstein Barr virus Mucocutaneous ulcer Hodgkin lymphoma Inflammatory bowel disease Crohn's disease

Current application of proteomics in biomarker discoveryfor inflammatory bowel disease

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world Journal of Gastrointestinal Pathophysiology 2016年第1期7卷 27-37页

作者： Patrick PY Chan Valerie C wasinger rupert w leong Bioanalytical Mass Spectrometry Facility Mark Wainwright Analytical Centrethe University of NSW AustraliaKensingtonNSW 2052Australia Gastroenterology and Liver Services Concord Repatriation General HospitalConcordNSW 2137Australia

Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease(IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD.

关键词： Proteomics Inflammatory bowel disease Biomarkers Molecular diagnostic techniques Massspectrometry

The pathogenesis of primary pouchitis following ileal pouch-anal anastomosis: a review of current hypotheses

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Open Journal of Gastroenterology 2011年第2期1卷 7-12页

作者： Sally Bath Christian P. Selinger rupert w.L. leong 不详

Primary pouchitis is a common complication of ileal pouch-anal anastomosis following proctocolectomy in patients treated for ulcerative colitis (UC), but is un-usual for those treated for familial adenomatous polyposis (FAP). while a number of theories as to the pathogenesis of this inflammatory condition have been proposed, no single one has been wholly satis-factory. Much research has been devoted to investi-gating a link between the pathogenic factors involved in UC, but not FAP, and those underlying pouchitis. The contribution of sulfate-producing bacteria has also been explored. The role of other intraluminal factors, such as short chain fatty acids and unconju-gated bile salts, has also been investigated. A unifying theory of a multi-step process might explain the pathogenesis of pouchitis, but further research is re-quired to proof causation. It is likely that pouchitis develops as a result of a combination of genetic, im-munological, microbial and metabolic factors. Future insight into the causes of pouchitis may eventually allow for the development of more effective treat-ments.

关键词： Pouchitis Ileo-pouch Anal Anastomosis Pathogenesis

Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: A review of the literature

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world Journal of Gastroenterology 2014年第27期20卷 8783-8789页

作者： Rosy wang rupert leong Gastroenterology and Liver Services Concord Hospital

To examine and evaluate recent evidence regarding the epidemiology, pathogenesis and management of colorectal cancer(CRC) development in inflammatory bowel disease(IBD)-primary sclerosing cholangitis(PSC) patients. Using the PubMed database, a literature search was conducted for relevant articles in English from the past 10 years. Relevant studies investigating PSC as a risk factor for CRC in IBD in the context of incidence and prevalence, pathogenesis, prevention and prognosis were included in this review. Recent evidence increasingly points to PSC as a significant risk factor in the development of CRC in patients with concomitant IBD. PSC may be an important risk factor for CRC in different populations worldwide. The mechanism for this increase in risk is still unclear. The efficacy of UDCA as a chemopreventive agent remains controversial. Liver transplantation does not halt the development of CRC, although there is not enough evidence to suggest that it is associated with increased incidence of CRC. while routine colonoscopic surveillance should be performed in patients with concurrent PSC and IBD, more high-level evidence is required to support the benefits of the procedure. while many new developments have taken place in the last decade, the pathogenesis and optimal management of CRC development in IBD-PSC patients remain unclear.

关键词： Primary sclerosing cholangitis Ulcerative colitis Crohn's Inflammatory bowel disease Colorectal cancer Liver transplantation Ursodeoxycholic acid