Publications by authors named "Daniel Van Langenberg"
Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial.
Lancet Gastroenterol Hepatol
November 2024
Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC.
Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1).
Article Synopsis
- Thiopurine co-therapy with anti-TNFα agents improves drug levels and reduces the chance of developing antibodies in patients with inflammatory bowel disease (IBD).* -
- A study analyzed the relationship between 6-thioguanine nucleotide (6-TGN) levels and anti-TNFα levels among IBD patients from 2015 to 2021, showing a significant link with infliximab but not adalimumab.* -
- The research identified optimal 6-TGN cut-off levels for effective therapeutic anti-TNFα levels, suggesting lower levels may suffice for treatment, particularly for infliximab.*
Background: The optimal infliximab dose intensification strategy to address loss of response associated with subtherapeutic infliximab trough levels remains uncertain, as does whether post-intensification trough and treatment targets should influence this decision.
Objectives: This pharmacokinetic simulation study aimed to identify infliximab dose intensification strategies capable of achieving post-intensification infliximab trough thresholds associated with clinical and objective treatment targets in Crohn's disease and ulcerative colitis.
Methods: A validated pharmacokinetic infliximab model, applied to 200 simulated patients, identified those with subtherapeutic (< 3.
Background: Serum free thiols (SFTs) reflecting oxidative stress appear to correlate with inflammatory bowel disease (IBD) activity. We aimed to evaluate the performance of SFTs concentrations vs endoscopic and histological activity, compare SFTs with established biomarkers, and identify clinical and laboratory parameters independently associated with SFT levels in IBD patients.
Methods: Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited, with serum samples obtained concurrently for SFTs and routine bloods, plus fecal calprotectin and immunochemical tests were collected ±30 days from ileocolonoscopy.
Background And Aim: Capsule endoscopy allows the direct visualization of the small bowel. We examined the diagnostic utility of a new modality, namely panenteric Crohn's capsule endoscopy (CE), in detecting active small-bowel Crohn's disease (CD) in those with normal magnetic resonance enterography (MRE).
Methods: We prospectively recruited patients with a diagnosis of CD or suspected small-bowel CD in whom the MRE was normal.
Background: Thiopurines are established treatments for inflammatory bowel disease (IBD), yet concerns remain regarding their safety.
Aim: To evaluate the use of thiopurine-allopurinol combination therapy compared to standard thiopurine therapy in IBD.
Methods: We performed a multicentre, randomised, placebo-controlled trial to compare the efficacy and safety of thiopurine-allopurinol versus thiopurine with placebo for adults commencing a thiopurine for IBD.
Article Synopsis
- Faecal calprotectin is the main biomarker used to monitor Crohn's disease activity, but other potential biomarkers exist.
- A meta-analysis of studies from 1978 to August 2022 assessed the effectiveness of these faecal biomarkers in determining endoscopic activity and mucosal healing.
- The analysis found faecal calprotectin and faecal lactoferrin to have promising sensitivity and specificity for distinguishing between active and inactive disease, with calprotectin still being the most reliable biomarker, though more research on novel biomarkers is suggested.
Article Synopsis
- Crohn's disease (CD) is a chronic disorder primarily affecting the intestine, with treatment focused on achieving mucosal and transmural healing through various imaging techniques.
- A recent focus on histological healing requires frequent endoscopic exams, making non-invasive assessments like magnetic resonance enterography (MRE) increasingly important.
- This review will evaluate how MRE can effectively detect disease activity in CD and address challenges in monitoring activity post-surgery and when standard scopes show normal findings.
Article Synopsis
- The study compared two strategies for enhancing infliximab dosing in inflammatory bowel disease patients experiencing secondary loss of response: upfront re-induction vs. shortening the dose interval.
- Despite similar clinical response rates at weeks 12 and 32 between the two methods, they exhibited distinct pharmacokinetic profiles, with significant differences in infliximab levels at multiple time points.
- Factors such as disease activity at baseline and infliximab levels at specific weeks were found to predict treatment response at week 32, particularly noting that low week 2 levels indicated a higher risk of nonresponse.
Magnetic resonance enterography (MRE) is one of the most highly utilised tools in the assessment of patients with small bowel Crohn's disease (CD). As a non-invasive modality, it has both patient and procedure-related advantages over ileocolonoscopy which is the current gold standard for Crohn's disease activity assessment. MRE relies upon high-quality images to ensure accurate disease activity assessment; however, few studies have explored the impact of image quality on the accuracy of small bowel CD activity assessment.
View Article and Find Full Text PDFBackground: Despite growing awareness of the nocebo effect, few studies have evaluated the nocebo effect using combined assessment of patient-reported outcome measures (PROMs), clinical indices, and objective biomarkers in inflammatory bowel disease (IBD) patients switching from originator to biosimilar medicines.
Objective: This study aimed to compare these outcomes across switch and non-switch cohorts to evaluate the nocebo effect in patients with IBD.
Methods: Parallel cohorts of IBD patients who (1) switched from originator to biosimilar (CT-P13) infliximab and (2) continued biosimilar (CT-P13) infliximab were evaluated over 32 weeks.
Background: The thiopurine medications are well established in the treatment of inflammatory bowel disease (IBD). There is significant variation in levels of toxic and therapeutic metabolites. Current data from small or short-term studies support therapeutic drug monitoring (TDM) in assessing azathioprine (AZA) and 6-mercaptopurine (6MP).
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- Anti-TNF dose intensification can help patients with Crohn's disease who experience secondary loss of response (LOR), but some may not show improvement or maintain efficacy over time (tertiary non-response and LOR).
- A review of 26 studies showed a short-term response (within 12 weeks) varying from 33-90% and a sustained response (≥48 weeks) ranging from 25-85%, yet up to 45% might not respond within 6 months, and up to 64% could lose response beyond that timeline.
- While initial responses to intensification are promising, longer-term effectiveness is less certain, indicating the need for careful monitoring and potential alternative strategies for affected patients.
Article Synopsis
- Traditional predictive modeling for inflammatory bowel disease (IBD) primarily uses statistical regression methods, which struggle with complex data like repeated measurements; deep learning offers a promising alternative for discovering hidden relationships in clinical data.
- The study aimed to compare the effectiveness of deep learning against conventional algorithms in predicting the success of anti-TNF therapy in patients with Crohn's disease (CD).
- Analyzed data from 146 patients showed that after 12 months of treatment, 64% achieved remission, with deep learning algorithms potentially outperforming traditional methods based on their predictive models.
Article Synopsis
- Higher levels of anti-TNF drugs (infliximab and adalimumab) are linked to better clinical healing of Crohn's perianal fistulas and improved radiologic outcomes.
- A study analyzed 193 patients with perianal fistulising Crohn's disease, comparing drug levels and MRI results to determine healing status and radiologic remission.
- Results showed that patients with higher drug levels had significantly better radiologic healing and remission scores, indicating a positive correlation between drug concentration and reduced disease activity.
Article Synopsis
- The study aimed to analyze the effectiveness of infliximab treatment in patients with steroid-refractory acute severe ulcerative colitis (ASUC) and examine the relationships of specific serum biomarkers with the need for colectomy.
- A total of 94 patients were analyzed, and the results showed that 20% required colectomy within 12 months, with day 3 post-infliximab biomarkers like CRP-albumin-ratio (CAR) and CRP-lymphocyte-ratio (CLR) being significant indicators for predicting nonresponse and potential colectomy.
- The findings suggest that CAR and CLR can serve as effective predictive tools for colectomy risk, highlighting the need for further studies to validate these biomarkers
Faecal microbiota transplantation (FMT) is reportedly effective and safe for the management of recurrent or refractory Clostridioides difficile infection (CDI), yet real-world data of outcomes of FMT in Australia are limited. In this series, FMT safely resulted in resolution of CDI in 19 patients with reduced healthcare utilisation after 25 FMT, but one patient was diagnosed with an anti-nuclear antibody-positive constitutional illness and Hashimoto thyroiditis following FMT. Further prospective evaluation of the utility of FMT earlier in CDI treatment algorithms to minimise cost and morbidity, and recipient follow up for immune-mediated conditions, is required.
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