Background and Aims: The Pharmacovigilance Risk Assessment Committee (PRAC) proposed measures to address severe side effects linked to Janus kinase inhibitors (JAKi) in immune-mediated inflammatory... Show moreBackground and Aims: The Pharmacovigilance Risk Assessment Committee (PRAC) proposed measures to address severe side effects linked to Janus kinase inhibitors (JAKi) in immune-mediated inflammatory diseases (IMID). Use of these medications in individuals aged 65 and older, those at high cardiovascular risk, active or former long-term smokers, and those with increased cancer risk should be considered only if no alternatives exist. Caution is advised when administering JAKi to patients at risk of venous thromboembolism. We aim to implement recommendations from regulatory guidelines based on areas of uncertainty identified. Methods: A two-round modified Research and Development/University of California Los Angeles appropriateness methodology study was conducted. A panel of 21 gastroenterologists, dermatologists and rheumatologists used a 9-point Likert scale to rate the appropriateness of administering a JAKi for each proposed clinical scenario. Scores for appropriateness were categorized as appropriate, uncertain, or inappropriate. Two rounds were performed, each with online surveys and a virtual meeting to enable discussion and rating of each best practice. Results: Round 1 involved participants rating JAKi appropriateness and suggesting descriptors to reduce uncertainty. Survey results were discussed in a virtual meeting, identifying areas of disagreement. In round 2, participants rated their agreement with descriptors from round 1, and the level of uncertainty and disagreement reduced. Age flexibility is recommended in the absence of other risk factors. Active counseling on modifiable risks (e.g., overweight, mild hyperlipidemia and hypertension) and smoking cessation is advised. Uncertainty persists regarding cancer risk due to various factors. Conclusions: We outlined regulatory guidance without a personalized evaluation of the patient's risk profile might lead to uncertainty and become an arid technicality. Therefore, we identified gaps and implemented PRAC recommendations to help health professionals in clinical practice. Show less
De ziekte van Crohn (CD) en colitis ulcerosa (UC) zijn chronisch inflammatoire darmziekten (IBD). Ondanks dat er de laatste jaren significante stappen zijn gezet in de medicamenteuze behandeling... Show moreDe ziekte van Crohn (CD) en colitis ulcerosa (UC) zijn chronisch inflammatoire darmziekten (IBD). Ondanks dat er de laatste jaren significante stappen zijn gezet in de medicamenteuze behandeling van IBD, ervaart een groot deel van de IBD patiënten klachten van aanhoudende ontsteking en bijwerkingen van de behandeling, wat de noodzaak voor het zoeken naar nieuwe behandelingsopties onderstreept. Door ons te richten op zowel de ontsteking die de klachten van IBD veroorzaakt, als op de onderliggende pathogenese die deze ontsteking aanstuurt middels het introduceren van een gezond microbioom en een gebalanceerde leefstijl, hopen we een (kleine) stap voorwaarts gezet te hebben richting een toekomst met een betere kwaliteit van leven voor patiënten met IBD. Show less
Inflammatoire darmziekten (Inflammatory Bowel Disease, IBD) zijn chronische immuun-gemedieerde ziekten van het maag-darmstelsel. Het aandeel oudere patiënten met IBD, 65 jaar of ouder, wordt... Show moreInflammatoire darmziekten (Inflammatory Bowel Disease, IBD) zijn chronische immuun-gemedieerde ziekten van het maag-darmstelsel. Het aandeel oudere patiënten met IBD, 65 jaar of ouder, wordt groter. Het behandelen van deze groep is een uitdaging, omdat zij vaak andere ziekten (comorbiditeit) hebben en geriatrische aandoeningen zoals geheugenproblemen of verminderde spiermassa. Deze aandoeningen vallen onder het begrip kwetsbaarheid, en worden gemeten met een geriatrisch assessment.Dit proefschrift richt zich op het in kaart brengen van de huidige literatuur en behandeloverwegingen bij oudere patiënten met IBD, om daarna als een van de eersten bewijs te leveren voor het invoeren van (screening naar) comorbiditeit en kwetsbaarheid bij de behandeling van oudere patiënten met IBD.Allereerst wordt onderzocht welke factoren bijdragen aan behandelbeslissingen, door behandelaren te interviewen. Leeftijd en aspecten van kwetsbaarheid beïnvloeden behandelbeslissingen, maar behandelaren verschillen onderling in hoe ze deze aspecten gebruiken. Daarnaast liet een literatuur zoektocht zien dat het bewijs over de relatie tussen kwetsbaarheid en behandeluitkomsten schaars is.Ook wordt het verband tussen comorbiditeit en veiligheid van biologicals, medicijnen die ontstekingseiwitten of afweercellen remmen, onderzocht. De aanwezigheid van meer comorbiditeit geeft een hoger risico op bijwerkingen (infecties en ziekenhuisopnames), een hogere leeftijd geeft dat niet.Tenslotte wordt de prevalentie van kwetsbaarheid in een Nederlands cohort van oudere patiënten met IBD onderzocht. Bij ongeveer de helft was er kwetsbaarheid. Hoe kwetsbaarder, hoe hoger de IBD-ziekteactiviteit en de IBD-ziektelast. Kwetsbare patiënten hadden, onafhankelijk van hun leeftijd en IBD-ziekteactiviteit, een hogere kans op ziekenhuisopnames en infecties, maar ook op achteruitgang in zelfstandigheid en kwaliteit van leven. Show less
Inflammatory Bowel Diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunological digestive diseases with a progressive character and associated with significant... Show moreInflammatory Bowel Diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunological digestive diseases with a progressive character and associated with significant healthcare costs. Different solutions have been proposed such as innovation in care monitoring or implementation of electronic health (eHealth). IBD is one of many chronic diseases that could benefit from eHealth, adding smartphone applications to the toolbox for care management has the potential improve disease understanding, enhance medication adherence, improve patient-physician communications, and for earlier interventions by medical professionals when problems arise. Furthermore, the accessibility to Big Data and increased computational resources have paved the way for Artificial Intelligence (AI) to provide potential solutions for the management of prototypical complex diseases with advanced heterogeneity and alternating disease states, like IBD. In this thesis we assessed the current economic and psychosocial impact of IBD by assessing its effect on indirect costs, productivity and caregiving. Furthermore, we observed if we can proactively identify IBD patients’ needs using eHealth and Artificial Intelligence. Lastly, we analyze the impact of monitoring IBD patients using eHealth interventions in order to facilitate the delivery of high-value care. Show less
Asscher, V.E.R.; Vliet, Q. van der; Aalst, K. van der; Aalst, A. van der; Brand, E.C.; Meulen-de Jong, A.E. van der; ... ; Dutch ICC 2020
Purpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients >= 60 years. Methods Ninety IBD patients >= 60 years at initiation of anti-TNF... Show morePurpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients >= 60 years. Methods Ninety IBD patients >= 60 years at initiation of anti-TNF therapy, 145 IBD patients >= 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. Results In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185-12.973,p= .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098-9.790,p= .033) and the presence of multiple comorbidities (aHR 9.138 (1.248-66.935),p= .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. Conclusion Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients. Show less
It is increasingly recognized that in order to gain further insights into human disorders and develop new therapeutic strategies and diagnostic tools, it is critical to have a comprehensive... Show moreIt is increasingly recognized that in order to gain further insights into human disorders and develop new therapeutic strategies and diagnostic tools, it is critical to have a comprehensive overview of immune cell subsets resident in tissues under physiological and pathological conditions. Flow cytometry has been the golden standard for analyzing immune cell subsets, and with a typical experiment, dozens of immune subsets can be discriminated. Due to the lack of spectrally-resolvable fluorochromes, mass cytometry utilizing metal-conjugated antibodies has shown to be a powerful tool for dissecting the immune landscape even further. Inflammatory intestinal diseases can only be understood by studying specialized cell types within the tissue niche itself. In this thesis, we applied mass cytometry and data-driven, automated analysis approaches to investigate the complex compositions of heterogeneous cell subsets, such as those encountered in intestinal biopsies. These types of data have the potential to greatly improve our understanding of human disease. In concert with clinical data, mass cytometry could enable a finer classification of patients and might aid in the development of improved diagnostics, prognostics and personalized therapeutic regimens. Show less
