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Stevens-Johnson syndrome complicating adalimumab therapy in Crohn's disease

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World Journal of Gastroenterology 2009年第35期15卷 4449-4452页

作者： Muna Salama ian craig lawrance Department of Gastroenterology Fremantle HospitalFremantle 6059WAAustralia Department of Gastroenterology Fremantle HospitalWAAustralia Centre for Inflammatory Bowel Diseases Fremantle HospitalWA Australia Department of Medicine and Pharmacology University of Western AustraliaFremantle HospitalFremantle 6059WA Australia

The anti-tumor necrosis factor(TNF)αmedications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory *** the increasing number of patients receiving anti-TNFαagents,however,less common adverse reactions will *** eruptions complicating treatment with an anti-TNFαagent are not uncommon,occurring in around 20%of patients. Adalimumab,a fully humanized antibody against TNFα, may be expected to cause minimal immune-mediated skin reactions compared to the chimeric monoclonal antibody,***,however,report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with Crohn’ s disease(CD).In this case report,a 29-year-old male with colonic and perianal CD with associated erythema nodosum and large joint arthropathy developed severe mucositis,peripheral rash and desquamation,fevers and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after a 2 mo break from adalimumab *** biopsies of the abdominal wall confirmed erythema multiforme and the patient was on no other drugs and infective etiologies were *** patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson *** skin reactions have now been described in three of the TNFαantagonists(infliximab,etanercept and adalimumab).These reactions can be serious and prescribers need to be aware of the potential mucocutaneous side effects of these agents,especially as Stevens-Johnson syndrome is associated with significant morbidity and mortality.

关键词： TNF 肿瘤坏死因子治疗临床

Correlation of MRI-determined small bowel Crohn’s disease categories with medical response and surgical pathology

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World Journal of Gastroenterology 2009年第27期15卷 3367-3375页

作者： ian craig lawrance Christopher J Welman Peter Shipman Kevin Murray School of Medicine and Pharmacology University of Western AustraliaFremantle Hospital WA 6160 Australia Department of Gastroenterology Fremantle Hospital WA 6160 Australia Department of Radiology Fremantle Hospital WA 6160 Australia Statistical Consulting Group School of Mathematics and Statistics University of Western AustraliaWA 6160 Australia

AIM: To determine whether magnetic resonance imaging (MRI) can be used to categorize small bowel Crohn's disease (SB CD) into groups that correlate with response to medical therapy and surgical ***: Data was collected from all patients with MRI evidence of SB CD without significant colonic disease over a 32-mo period. Two radiologists, blinded to clinical findings, evaluated each MRI and grouped them based on bowel wall thickness and wall enhancement. These categories were: (1) "fibrosis", (2) "mild segmental hyper-enhancement and mild wall thickening", (3) "mild segmental hyper-enhancement and marked wall thickening", (4) "marked segmental transmural hyper-enhancement". Patient response to additional medical therapy post-MRI was prospectively determined at 8-wk. Non-responders underwent endoscopy and were offered therapeutic endoscopy or surgery. Surgical pathology was assessed against the MRI category. RESULTS: Fifty-five patients were included. Females and category "2" patients were more likely, and patients with luminal narrowing and hold-up less likely, to respond to medical therapy (P < 0.05). Seventeen patients underwent surgery. The surgical pathologicalfindings of fibrosis and the severity of inflammation correlated with the MRI category in all ***: Our fi ndings suggest that SB CD can be grouped by the MRI f indings and that these groups are associated with patients more likely to respond to continued medical therapy. The MRI categories also correlated with the presence and level of intestinal inflammation and fibrosis on surgical pathology, and may be of prognostic use in the management of CD patients.

关键词：病理反应 MRI 小肠外科医疗

Novel topical therapies for distal colitis

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2010年第5期1卷 87-93页

作者： ian craig lawrance Centre for Inflammatory Bowel Diseases Department of Gastroenterology Fremantle Hospital Fremantle 6059 WA Australia University Department of Medicine and Pharmacology University of Western Australia Fremantle Hos- pital Fremantle 6059 WA Australia

Distal colitis(DC) can be effectively treated with topical 5ASA *** target the rectum while enemas can reliably reach the splenic *** in combination with oral 5ASAs,the control of the inflammation is even more ***,resistant DC does occur and can be extremely challenging to *** these patients,the use of steroids,immunosuppressants and the anti-tumor necrosis factor α agents are often ***,however,can be associated with systemic side effects and are not always *** investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are *** of the agents that have been proposed for use in resistant distal colitis include butyrate,cyclosporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus,ecabet sodium,arsenic,lidocaine,rebamipide and Ridogrel *** of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small open-labelled patient *** work is thus required with the investigation of promising agents in the context of randomized double-blinded placebo controlled *** review aims to highlight those potentially effective therapies in the management of resistant distal colitis and to promote interest in furthering their investigation.

关键词： Resistant proctitis Tacrolimus Treatment Topical

Use of infliximab in the prevention and delay of colectomy in severe steroid dependant and refractory ulcerative colitis

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World Journal of Gastroenterology 2008年第16期14卷 2544-2549页

作者： Robert P Willert ian craig lawrance Department of Gastroenterology Fremantle Hospital

AIM: To determine if infliximab can prevent or delay surgery in refractory ulcerative colitis (UC). METHODS: UC patients who failed to have their disease controlled with conventional therapies and were to undergo colectomy if infliximab failed to induce a clinical improvement were reviewed. Patients were primarily treated with a single 5 mg/kg infliximab dose. The Colitis Activity Index (CAI) was used to determine response and remission. Data of 8 wk response and colectomy rates at 6 mo and 12 mo were collected. RESULTS: Fifteen patients were included, 7 with UC unresponsive or intolerant to Ⅳ hydrocortisone, and 8 with active disease despite oral steroids (all but one with therapeutic dosage and duration of immunomodulation). All the Ⅳ hydrocortisone-resistant/intolerant patients had been on azathioprine/6-MP < 8 wk. At 8 wk, infliximab induced a response in 86.7% (13/15) with 40% in remission (6/15). Within 6 mo of treatment 26.7% (4/15) had undergone colectomy and surgery was avoided in 46.6% (7/15) at 12 mo. The colectomy rate at 12 mo in those on immunomodulatory therapy < 8 wk at time of infliximab was 12.5% (1/8) compared with 100% (7/7) in patients who were on long-term maintenance immunomodulators (P < 0.02). CONCLUSION: Infliximab prevented colectomy due to active disease in immunomodulatory-na?ve, refractory UC patients comparable to the use of Cyclosporine. In patients, however, on effective dosage and duration of immunomodulation at time of infliximab therapy colectomy was not avoided.

关键词：急性肠炎治疗方法结肠切除术症状

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

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World Journal of Gastroenterology 2020年第30期26卷 4428-4441页

作者： Samba Siva Reddy Pulusu Ashish Srinivasan Krupa Krishnaprasad Daniel Cheng Jakob Begun CharlotteKeung Daniel Van Langenberg Lena Thin Tamara Mogilevski Peter De Cruz Graham Radford-Smith Emma Flanagan Sally Bell Soleiman Kashkooli Miles Sparrow Simon Ghaly Peter Bampton Elise Sawyer Susan Connor Quart-ul-ain Rizvi Jane M Andrews Gillian Mahy Paola Chivers Simon Travis ian craig lawrance Centre for Inflammatory Bowel Diseases St John of God HospitalSubiaco 6008Western AustraliaAustralia Translational Gastroenterology Unit NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Inflammatory Bowel Disease Research Group Queensland institute of Medical ResearchHerston 4006QueenslandAustralia Department of Gastroenterology Mater HospitalBrisbane 4101QueenslandAustralia Department of Gastroenterology Mater HospitalSouth Brisbane 4101QueenslandAustralia of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalFitzroy 3065VictoriaAustralia Department of Gastroenterology Northern HealthEpping 3076VictoriaAustralia Department of Gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalDarlinghurst 2010New South WalesAustralia Department of Gastroenterology Flinders Medical CentreBedford Park 5042South AustraliaAustralia Department of Gastroenterology Liverpool HospitalSydney 2170New South WalesAustralia Department of Gastroenterology Royal Adelaide Hospital&University of AdelaideAdelaide 5000South AustraliaAustralia Department of Gastroenterology Townsville HospitalDouglas 4814QueenslandAustralia Institute for Health Research University of Notre DameFremantle 6160Western AustraliaAustralia School of Medicine and Pharmacology University of Western AustraliaCrawley 6009Western AustraliaAustralia

BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)*** To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving *** A retrospective review of Australian and Oxford,United Kingdom data for UC *** response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were *** regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing *** outcomes were *** Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were *** clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo ***-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%Pian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 *** VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

关键词： Vedolizumab Ulcerative colitis Outcomes