Aliment Pharmacol Ther 2010; 32: 1007–1016
Summary
Background About 30–50% of patients with Crohn’s disease (CD) develop fistulae, implying significant disease burden and complicated clinical ...management.
Aim To assess appropriate use of therapy for fistulizing CD patients enrolled in the Swiss Inflammatory Bowel Disease Cohort using criteria developed by the European Panel on the Appropriateness of Crohn’s disease Therapy.
Methods Specific questionnaires were used to gather information on disease and its management. We assessed appropriateness of therapy at enrolment for adult CD patients with one or several fistulae.
Results Two hundred and eighty‐eight CD patients had fistulizing disease, of which 80% had complex fistulae and 32% currently had active draining fistulae. Mean age (s.d.) at diagnosis was 27 years (11), 51% males. Of the patients, 78% were judged as having globally an appropriate therapy, which was more often given for complex fistulae (87%) than for simple fistulae (67%). Antibiotics, azathioprine/MP, methotrexate and conservative surgery were almost always appropriate. Anti‐tumor necrosis factor α was considered globally appropriate (91%), although most often with an uncertain indication. The 5ASA compounds, steroids and aggressive surgery were most often inappropriate (84%, 58% and 86% respectively).
Conclusions Formal appropriateness criteria for CD therapy were applied to a national cohort of IBD patients. For more than three‐quarters of the patients with fistulizing CD, therapy was globally appropriate.
To summarize the published literature on assessment of appropriateness of colonoscopy for investigation of chronic diarrhea, management of patients with known inflammatory bowel disease (IBD), and ...for colorectal cancer (CRC) surveillance in such patients, and to report report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II.
A systematic search of guidelines, systematic reviews, and primary studies regarding the evaluation of chronic diarrhea, the management of IBD, and colorectal cancer surveillance in IBD was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions.
According to the literature, colonoscopic evaluation may be justified for patients aged > 50 years with recent-onset chronic diarrhea or with alarm symptoms. Surveillance colonoscopy for CRC should be offered to all patients with extensive ulcerative colitis or colonic Crohn's disease of 8 years' duration, and to all patients with less extensive disease of 15 years' duration. Intervals for surveillance colonoscopy depend on duration of evolution, initial diagnosis, and histological findings. The EPAGE II criteria also confirmed the appropriateness of diagnostic colonoscopy for diarrhea of > 4 weeks' duration. They also suggest that, in addition to assessing extent of IBD by colonoscopy, further colonoscopic examination is appropriate in the face of persistent or worsening symptoms. Surveillance colonoscopy in IBD patients was generally appropriate after a lapse of 2 years. In the presence of dysplasia at previous colonoscopy, it was not only appropriate but necessary.
Despite or perhaps because of the limitations of the available published studies, the panel-based EPAGE II (http://www.epage.ch) criteria can help guide appropriate colonoscopy use in the absence of strong evidence from the literature.
Abstract
Background
The oral selective JAK kinase inhibitor, Upadacitinib (UPA; Rinvoq®) has been shown to induce and maintain clinical response and remission in Crohn’s disease (CD), but also in ...rheumatic and skin diseases. We report here on the largest Swiss experience in "off label" use of this drug.
Methods
A chart review of the Crohn’s and Colitis Center Beaulieu Lausanne and Gastroenterology Center Bulle of CD patients was conducted.
Results
Eighty-nine IBD patients were exposed to UPA treatment. After exclusion of 22 patients (UC and unknown consent status) we analyzed patients’ characteristics of 67 CD patients (72% women) treated between April 2019 and Nov. 2023. All patients had previously failed or were intolerant to, at least, one anti-TNF agent, 75% had been exposed to 4 or more biologics/ small molecules and two-third had received all classes of biologics. Disease location and behavior were mostly ileo-colonic and inflammatory (L3B1) or ileal only and stricturing (L1B2). Half of the patients had co-existing extraintestinal manifestations (mostly spondylarthritis and arthralgias). Advanced combination therapy was used in 27% of cases with anti-TNF agents (n=10), vedolizumab (n=6) and ustekinumab (n=2). UPA was prescribed after a median disease duration of 14 years (range 1-68) for a mean treatment duration of 14 months (mo) (+/- 9.1 SD; range 1-37). Forty-four CD patients (66%) were still on UPA at the time of study completion. A partial or complete response was observed in 51/67 patients (76%) with a mean decrease of CRP of 10.4 mg/l (+/- 17.6 SD) and calprotectin of 610 mcg/g (+/- 1165 SD). Adverse events were mostly viral infections, acnea, hypercholesterolemia, fatigue and headaches.
Conclusion
Upadacitinib is a good treatment option in difficult to treat CD patients with aggressive disease behavior, alone or in combination in case of concomitant rheumatic and gastrointestinal indications.
Abstract
Background
The treatment landscape of inflammatory bowel disease (IBD) has changed in the past decade with introduction of new drug classes. For most drugs, only 30% of patients achieve ...long-term remission. Clinical implementation of predictive biomarkers to support precision medicine is lacking. As the interactions of immune system and microbiome in the colonic mucosa may hold the key to the prediction problem, we performed a systematic review to assess the status of tissue-based biomarkers in the era of biological and small molecule therapies.
Methods
A literature search was performed in Medline, Embase, the Cochrane Library, Web of science and the ECCO abstract database in July 2023. Papers were considered eligible when reporting on biomarkers, extracted from biopsies obtained during colonoscopy, that had predictive value regarding therapy success of a specific non-TNFα biological or small molecule. Two authors independently assessed eligibility and extracted the data.
Results
From 10,141 screened records with 155 papers assessed for eligibility, a total of 43 studies were included. The majority was published in the last 5 years (87%). Data on the clinical history of patients and the interval between biopsy and therapy onset was often lacking, in part while 49% of studies were published as conference abstracts. Heterogeneity in therapy success assessment regarding modality (clinical, endoscopic, and/or histologic) and interval (4-58 weeks) was striking. With 28 studies, vedolizumab is the best investigated drug. Of the 16 studies reporting on gene expression, 7 used data from the GEMINI-I/LTS trials. These studies reported a range from a single predictive gene such as TREM1 and OSM to a classifier of 267 differentially expressed genes. Studies looking at the protein level (n=7) focused mostly on target engagement. In 7 studies, biomarker discovery was performed through histological evaluation, mainly looking at mucosal eosinophil counts. One study looking at the microbiome did not find differences between responders and non-responders of vedolizumab.
Conclusion
Our systematic review shows that tissue-based predictive biomarker discovery in IBD is a young and dynamic field of research. This is reflected by the heterogeneity in how and when therapy success is assessed. Moreover, the various methods to analyze gene expression data yield vastly different results when applied to the same dataset. We therefore propose guideline development to support clinical implementation of predictive biomarkers.
To summarize the published literature on assessment of appropriateness of colonoscopy for the investigation of functional bowel symptoms, and report appropriateness criteria developed by an expert ...panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II.
A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of functional bowel symptoms was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions.
Much of the evidence for use of colonoscopy in evaluation of chronic abdominal pain, and/or constipation and/or abdominal bloating is modest. Major limitations include small numbers of patients and lack of adequate characterization of these patients. Large community-based follow-up studies are needed to enable better definition of the natural history of patients with functional bowel disorders. Guidelines stress that alarm features ("red flags"), such as rectal bleeding, anemia, weight loss, nocturnal symptoms, family history of colon cancer, age of onset > 50 years, and recent onset of symptoms should all lead to careful evaluation before a diagnosis of functional bowel disorder is made. EPAGE II assessed these symptoms by means of 12 clinical scenarios, rating colonoscopy as appropriate, uncertain and inappropriate in 42 % (5/12), 25 % (3/12), and 33 % (4/12) of these, respectively.
Evidence to support the use of colonoscopy in the evaluation of patients with functional bowel disorders and no alarm features is lacking. These patients have no increased risk of colon cancer and thus advice on screening for this is not different from that for the general population. EPAGE II criteria, available online (http://www.epage.ch), consider colonoscopy appropriate in patients of > 50 years with chronic or new-onset bowel disturbances, but not in patients with isolated chronic abdominal pain.
Background: While quality of life (QoL) is a well‐recognised outcome measure of Crohn disease (CD) activity, its influence on other outcome measures, including exacerbation of CD is poorly ...understood. If QoL measures were to be associated with intestinal inflammatory activity, they might be useful for early detection of subclinical flares.
Aims: We hypothesised that low QoL might be associated with subsequent CD flares.
Methods: A cohort of 318 adult CD patients was observed for 1 year after assessment of baseline characteristics. Data were collected in Swiss university hospitals, regional hospitals and private practices. At inclusion, patients completed the Inflammatory Bowel Disease QoL Questionnaire (gastrointestinal QoL; range: 32 to 224 points) and the Short Form‐36 Health Survey (general QoL; range: 35 to 145 points). During follow up, flares were recorded. Binary logistic regression was performed to estimate the relation between QoL and the odds of subsequent flares.
Results: A twofold decrease in the odds of flares (99% CI: 1.1; 4.0) per standard deviation of gastrointestinal QoL and a threefold decrease (99% CI: 1.5; 6.2) per standard deviation of general QoL were observed.
Conclusions: The close association between QoL and subsequent flares suggests that QoL measures might be useful in detecting upcoming flares before they become clinically apparent.
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