Publications by authors named "Lena Thin"

11 Publications

  • Page 1 of 1

Editorial: outcomes following a second switch-evaluating clinical outcomes and patient perspectives in IBD.

Aliment Pharmacol Ther 2021 05;53(9):1038-1039

Department of Gastroenterology, Fiona Stanley Hospital, Perth, WA, Australia.

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May 2021

The Effect of Adiposity on Anti-Tumor Necrosis Factor-Alpha Levels and Loss of Response in Crohn's Disease Patients.

Clin Transl Gastroenterol 2020 09;11(9):e00233

Department of Gastroenterology, Fiona Stanley Hospital, Murdoch, Australia.

Introduction: A high body mass index is known to adversely affect antitumor necrosis factor-alpha trough levels and secondary loss of response (SLOR) in patients with Crohn's disease. We hypothesize that high levels of adiposity negatively affect these outcomes and aimed to determine if this relationship exists.

Methods: We performed a retrospective cross-sectional study of 69 patients with Crohn's disease from two tertiary inflammatory bowel disease centers between February 1, 2015, and June 30, 2018. Primary responders to infliximab (IFX) or adalimumab (ADA) who had a trough level performed within 6 months of CT or MRI scan and at least 12 months of clinical follow-up were eligible for inclusion. Body composition as measured on CT/MRI scans were correlated with trough concentration and time SLOR. Multivariate adjustments were made for established risk factors known to affect trough levels and SLOR.

Results: Of 69 included patients, 44 (63.8%) and 25 (36.2%) patients received IFX and ADA, respectively. Multivariate analysis revealed that IFX trough concentrations were inversely correlated with visceral fat area (-0.02 [-0.04, -0.003], P = 0.03), visceral fat index (-0.07 [-0.12, -0.01], P = 0.02) and visceral fat: skeletal muscle area ratio (-3.81 [-7.13, -0.50], P = 0.03), but not body mass index (-0.23 [-0.52, 0.06], P = 0.11). No predictive factors were found for ADA. Increased total adipose area was associated with an increased risk of SLOR in ADA-treated patients, but not IFX-treated patients (hazard ratio = 1.01 [1.002, 1.016], P = 0.011).

Discussion: Visceral adiposity is an important predictor of IFX trough levels, and high total adiposity predicts for SLOR to ADA.
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September 2020

Switching Australian patients with moderate to severe inflammatory bowel disease from originator to biosimilar infliximab: a multicentre, parallel cohort study.

Med J Aust 2021 02 17;214(3):128-133. Epub 2020 Oct 17.

Fiona Stanley Hospital, Perth, WA.

Objective: To examine whether non-medical switching of patients with inflammatory bowel disease (IBD) from originator infliximab to a biosimilar (CT-P13, Inflectra) is safe and clinically non-inferior to continued treatment with originator infliximab.

Design: Prospective, open label, multicentre, parallel cohort, non-inferiority study in seven Australian hospitals over 48 weeks, May 2017 - October 2019.

Participants: Adults (18 years or older) with IBD receiving maintenance originator infliximab (Remicade) who had been in steroid-free clinical remission for at least 12 weeks.

Intervention: Managed program for switching patients in four hospitals from originator to biosimilar infliximab (CT-P13); patients in three other hospitals continued to receive originator infliximab (control).

Main Outcome Measures: Clinical disease worsening requiring infliximab dose escalation or change in therapy.

Results: The switch group included 204 patients, the control group 141 patients with IBD. Ten patients in the control group (7%) and 16 patients switched to CT-P13 (8%) experienced clinical deterioration; the adjusted risk difference (control v switch group) was -1.1 percentage points (95% CI, -6.1 to 8.2 percentage points), within our pre-specified non-inferiority margin of 15 percentage points. Serious adverse events leading to infliximab discontinuation were infrequent in both the switch (six, 3%) and control (six, 4%) groups.

Conclusion: Switching patients with IBD from originator to biosimilar infliximab is safe and non-inferior to continuing treatment with originator infliximab. Moreover, the introduction of biosimilar infliximab, by increasing market competition, has resulted in substantial cost savings for the Pharmaceutical Benefits Scheme.
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February 2021

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

World J Gastroenterol 2020 Aug;26(30):4428-4441

Centre for Inflammatory Bowel Diseases, St John of God Hospital, Subiaco 6008, Western Australia, Australia.

Background: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients.

Aim: 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 remission.

Methods: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded.

Results: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% 70% = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% 40% < 0.001, 6 mo 73% 46% < 0.001, 12 mo 66% 51% = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% 43% = 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 ( < 0.001). 32 patients (11%) had colectomy by 12 mo.

Conclusion: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.
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August 2020

Ileocolonic End-to-End Anastomoses in Crohn's Disease Increase the Risk of Early Post-operative Endoscopic Recurrence in Those Undergoing an Emergency Resection.

J Gastrointest Surg 2021 01 6;25(1):241-251. Epub 2020 May 6.

School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Highway, Perth, Western Australia, 6150, Australia.

Background And Aim: Several risk factors affecting post-operative recurrence in Crohn's disease patients have been studied, and of these, the role of the anastomosis remains contentious. We aimed to compare the risk of developing early post-operative endoscopic recurrence (EPER), in resections that had an end-to-end anastomosis (ETEA) to a side-to-side anastomosis (STSA).

Methods: All Crohn's disease patients that underwent an ileocolic or small bowel resection between January 2012 and June 2017 at two tertiary IBD centres were reviewed retrospectively. Included patients had a minimum of 12-month clinical follow-up and a colonoscopy within 12 months of the resection or stoma reversal. Univariate and multivariate binary logistic regression analyses determined the independent risk factors for early post-operative endoscopic recurrence, defined as a Rutgeerts score of ≥ i2b.

Results: Ninety-two resections associated with an ETEA or a STSA were included for analysis. The ETEA was the most common anastomosis, constructed in 55 patients (59.8%). Forty-nine operations (53.3%) resulted in a ≥ i2b recurrence at the first surveillance colonoscopy. The multivariate analysis showed that there was no difference between the ETEA and STSA in determining the odds ratio (OR) for developing EPER (OR = 2.41 (0.95-6.05), P = 0.06). In those that underwent a resection emergently however, the significant determinants of EPER were as follows: having an ETEA (OR = 38.12 (2.44-595.87), P = 0.01), failing to commence a biologic and/or an immunosuppressant early (OR = 24.21 (1.69, 347.81), P = 0.02), and active smoking (OR = 7.19 (1.12-46.21), P = 0.04).

Conclusion: The ETEA is best avoided in those undergoing an emergency resection. The early commencement of a biologic and/or an immunosuppressant and smoking cessation is imperative this high-risk group of patients.
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January 2021

Swiss cheese tragedy case study.

Lena W Y Thin

J Gastroenterol Hepatol 2018 Sep;33 Suppl 3:31-32

Department of Gastroenterology, Fiona Stanley Hospital, Perth, Western Australia, Australia.

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September 2018

Entyvio lengthen dose-interval study: lengthening vedolizumab dose interval and the risk of clinical relapse in inflammatory bowel disease.

Eur J Gastroenterol Hepatol 2018 07;30(7):735-740

Gastroenterology and Liver Services, Concord Repatriation General Hospital.

Background: Vedolizumab (VDZ), an α4β7 anti-integrin antibody, is efficacious in the induction and maintenance of remission in ulcerative colitis (UC) and Crohn's disease (CD). In the GEMINI long-term safety study, enrolled patients received 4-weekly VDZ. Upon completion, patients were switched to 8-weekly VDZ in Australia. The clinical success rate of treatment de-escalation for patients in remission on VDZ has not been described previously.

Aim: To determine the proportion of patients who relapsed after switching from 4 to 8-weekly VDZ, the mean time to relapse, and the recapture rate when switching back to 8-weekly dosing.

Materials And Methods: This was a retrospective, observational, multicenter study of patients previously recruited into GEMINI long-term safety in Australia. Data on the demographics and biochemical findings were collected.

Results: There were 34 patients [23 men, mean age 49.1 (±13.1) years] and their mean disease duration was 17.6 (±8.5) years. The mean 4-weekly VDZ infusion duration was 286.5 (±48.8) weeks. A total of five (15%) patients relapsed on dose-interval increase (4/17 UC, 1/17 CD) at a median duration from dose interval lengthening to flare of 14 weeks (interquartile range=6-25). Eighty percent (4/5) of patients re-entered remission following dose-interval decrease back to 4-weekly. No clinical predictors of relapse could be determined because of the small cohort size.

Conclusion: The risk of patients relapsing when switching from 4 to 8-weekly VDZ ∼15% and is similar between CD and UC. Dose-interval decrease recaptures 80% of patients who relapsed. Therapeutic drug monitoring of VDZ may be of clinical relevance.
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July 2018

Oral tacrolimus for the treatment of refractory inflammatory bowel disease in the biologic era.

Inflamm Bowel Dis 2013 Jun;19(7):1490-8

Centre for Inflammatory Bowel Diseases, Fremantle Hospital, Fremantle, Australia.

Background: Patients with inflammatory bowel disease who are refractory to standard therapies frequently require surgery. The long-term efficacy of tacrolimus in patients who fail standard immunosuppressive and antitumor necrosis factor α therapy is unknown.

Methods: Thirty-five patients (11 Crohn's disease and 24 ulcerative colitis) with medication-resistant disease were treated with oral tacrolimus and reviewed retrospectively. Patients were commenced on tacrolimus 0.1 mg/kg/day, with a trough level targeted between 8 and 12 ng/mL. Clinical response or remission at 30 days, 90 days, and 1 year was assessed. The overall risk of requiring surgery and predictive factors were also assessed.

Results: All patients had failed a thiopurine, 5 (14%) had also failed methotrexate, while 90% had a primary or secondary nonresponse, or an incomplete response, to an antitumor necrosis factor α agent. The proportions that achieved a clinical response at 30 days, 90 days, and 1 year was 65.7%, 60%, and 31.4%, respectively, whereas the corresponding proportions in remission were 40%, 37.1%, and 22.9%. The cumulative risk of requiring surgery was 40.4% at 1 year and 59.3% at 2 years with a median time to surgery of 22 months (range, 0.5-84 months). Patients who were steroid refractory, or dependent, before starting tacrolimus were more likely to have surgery (P = 0.006), whereas patients who were able to achieve or maintain a clinical response with tacrolimus by 90 days were less likely (P = 0.004).

Conclusions: Tacrolimus is able to induce a clinical response in a third and remission in a fifth of medically refractory patients with inflammatory bowel disease at 1 year. A 90-day therapeutic trial is worthwhile in difficult to treat patients.
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June 2013

IgG4-related sclerosing disease of the small bowel presenting as necrotizing mesenteric arteritis and a solitary jejunal ulcer.

Am J Surg Pathol 2012 Jun;36(6):929-34

Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Hospital Avenue, Nedlands 6009, Western Australia.

Since first described in the mid 1990s, there has been burgeoning literature on IgG4-related sclerosing disease. The number of sites that may be involved is ever increasing, with the pancreas, salivary glands, and lymph nodes being the most commonly affected organs. There are no well-documented cases arising in the gastrointestinal tract. In this report, we present the first case to our knowledge of IgG4-related sclerosing disease involving the small bowel with a distinctly unusual clinicopathologic presentation. A previously well 46-year-old woman presented with a 2-year history of intermittent abdominal pain with recent worsening due to small bowel obstruction. Following imaging, which showed jejunitis with surrounding mesenteric inflammatory changes, she proceeded to a segmental small bowel resection. The resected jejunum revealed an isolated, stenosing chronic ulcer associated with a necrotizing mesenteric arteritis. A transmural inflammatory infiltrate rich in IgG4 plasma cells was seen in the wall of the bowel and mesenteric artery. Abundant IgG4 interfollicular plasma cells were also identified in a mesenteric lymph node. The serum IgG4 level was elevated at >800 mg/dL (reference range 8 to 140 mg/dL). Although phlebitis is an almost constant feature of this disease, arteritis is not described other than in the lung and aorta. In this report, we also discuss the diagnostic pitfalls and the differential diagnoses that should be considered when this condition arises in the gastrointestinal tract.
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June 2012

Acute graft-versus-host disease after liver transplant: novel use of etanercept and the role of tumor necrosis factor alpha inhibitors.

Liver Transpl 2009 Apr;15(4):421-6

West Australian Liver Transplant Service, Perth, Western Australia, Australia.

Acute graft-versus-host disease following orthotopic liver transplantation is a rare but feared complication arising in 1% to 2% of cases with a dismal prognosis. It most often presents as fever, rash, and diarrhea with or without pancytopenia. Patients die from complications of marrow failure such as sepsis or bleeding. Because of its low incidence, there is no clear treatment protocol for this complication. Both increasing and withdrawing immunosuppression have been attempted with variable success. Although anti-tumor necrosis factor alpha therapy has been widely used for the treatment of steroid-resistant acute graft-versus-host disease in the hematopoietic stem cell transplant setting, there previously have been no reported cases of its use in liver transplantation. The aim of this report is to review a case of acute graft-versus-host disease and the use of etanercept to manage this complication. Etanercept has never previously been used in liver transplantation complicated by acute graft-versus-host disease. In the hematology literature, the success of its use is offset by significant rates of serious infectious (especially fungal) complications. However, preliminary results are encouraging and offer insight into its use as a potentially viable therapeutic option. We report the first successful use of etanercept in liver transplantation-associated graft-versus-host disease, albeit complicated by invasive aspergillosis, and recommend concurrent antifungal prophylaxis when the drug is used in this setting.
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April 2009