Therapeutic Advances in Gastroenterology最新文献

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice.

Background: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability.

Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients.

Design: Data included patients from the Placebo-controlled UC cohort (phase II OASIS, and phase III ELEVATE UC 52 and ELEVATE UC 12 trials) receiving QD etrasimod (2 or 1 mg) or placebo.

Methods: Proportions and incidence rates (IRs; the number of patients with a TEAE divided by the total exposure in patient-years (PYs), per 100 PY) of Headache, Pyrexia, Nausea and Dizziness TEAEs were reported. Changes in heart rate among patients with Dizziness TEAEs were also evaluated.

Results: Among 943 patients (etrasimod 2 mg, N = 577 (276.7 PY); etrasimod 1 mg, N = 52 (11.4 PY); placebo, N = 314 (115.1 PY)), 48, 34, 27 and 21 patients experienced events of Headache, Pyrexia, Nausea and Dizziness, respectively. All events were non-serious; one patient treated with etrasimod was discontinued due to a Pyrexia TEAE. Numerically, IRs of Headache and Dizziness TEAEs were higher, and Nausea slightly higher, with etrasimod versus placebo (13.45 vs 8.63 per 100 PY, 6.52 vs 1.69 and 7.18 vs 5.13 per 100 PY, respectively); IRs were similar for Pyrexia. The duration of most TEAEs was 1-10 days.

Conclusion: In the etrasimod UC clinical programme, all Headache, Pyrexia, Nausea and Dizziness events were non-serious. Headache and Dizziness were more frequent, and Nausea slightly more frequent, among patients receiving etrasimod versus placebo. The post hoc nature of this analysis is a limitation. These results reiterate the favourable safety profile and tolerability of etrasimod.

Trial registration: ClinicalTrials.gov: NCT02447302; NCT03945188; NCT03996369.

Background: The efficacy of ustekinumab (UST) and infliximab (IFX) in Crohn's disease (CD) patients with intestinal stenosis remains uncertain.

Objective: This study aims to compare the efficacy of UST and IFX in the treatment of CD patients with intestinal stenosis.

Design: This was a retrospective and multicenter cohort study.

Methods: In this retrospective study, we included CD patients treated with IFX or UST at five centers. We assessed the clinical response rate at weeks 12 and 24, steroid-free clinical remission rate at weeks 24 and 52 for overall patients and those with stenosis, and objective examination (intestinal ultrasound and/or endoscopy) response rate at week 52 for stenosis patients.

Results: A total of 211 CD patients (106 IFX and 105 UST) were included, with 119 (56 IFX and 63 UST) having intestinal stenosis. In the overall patient population, there were no significant differences in clinical response rate and steroid-free clinical remission rate at weeks 12, 24, and 52 between the IFX and UST groups. In patients with stenosis, the steroid-free clinical remission rate at week 52 was significantly lower in the IFX group compared to the UST group (51.79% IFX vs 69.84% UST, p = 0.044). The objective examination response rate did not significantly differ between the IFX and UST groups at week 52 (66.67% IFX vs 76.19% UST, p = 0.690). In the UST group, steroid-free clinical remission rate was higher in bio-naïve patients than bio-experienced patients at week 24 (75.00% bio-naïve vs 55.38% bio-experienced, p = 0.043).

Conclusion: UST may be considered a more advantageous treatment option for those CD patients with intestinal stenosis, as it has better steroid-free clinical remission rates compared to IFX.

Background: Esophagogastroduodenoscopy (EGD) is the gold standard method for diagnosing upper gastrointestinal (GI) pathology. Swedish guidelines recommend patients over 50 years with new-onset dyspeptic symptoms undergo direct gastroscopy to rule out malignancy. However, the incidence of dysplasia or cancer in patients aged 61-70 years remains unclear.

Objectives: To investigate the referral factors and endoscopic findings in patients aged 61-70 years and compare the result with age groups 51-60 and 41-50 years from our previous studies to establish whether there is an age cutoff for upper GI cancer risk.

Design: A retrospective observational study was conducted to evaluate EGD referrals and outcomes in patients aged 61-70 years.

Methods: We analyzed EGD referrals for patients aged 61-70 years within Region Örebro County from January 2019-April 2020 to January 2022-2023. Clinical data, including symptoms, medications, and laboratory results, were collected from medical records. Statistical analysis, including odds ratios (OR) and positive predictive values (PPV), was conducted to evaluate pathological outcomes based on referral factors.

Results: A total of 1003 referrals were analyzed. Statistically significant differences in pathological findings were observed between the 41-50 years reference group and the older groups (51-60 years: OR 2.08, p < 0.001; 61-70 years: OR 3.05, p < 0.001). However, no statistically significant difference in cancer incidence was found between the age groups.

Conclusion: The most common pathological findings were benign, including hiatal hernia, gastroesophageal reflux disease/esophagitis, or gastritis. The incidence of cancer was low in all three groups. These results suggest that the "test-and-treat" strategy, currently recommended for patients under 50 years, may be appropriate for patients aged 51-70 years as well.

Trial registration: NCT04585516.

Background: Independent use of artificial intelligence with computer-aided detection (CADe) and Endocuff Vision (ECV) has demonstrated enhanced adenoma detection rates (ADRs).

Objective: Our pilot study aimed to define the necessary participant number for future randomized controlled trials (RCTs) by comparing the ADR of combined CADe + ECV against CADe alone and standard colonoscopy.

Design: This single-center pilot study retrospectively analyzed a prospectively maintained database, where patients underwent screening colonoscopies sequentially by standard method, CADe alone, and then CADe + ECV.

Method: The allocation of the technique depended on the study period. Patients were randomly selected from the cohort to form three groups of 30 patients, with stratification based on factors influencing the ADR. The primary endpoint was the ADR.

Results: From April to June 2021, 244 patients underwent screening colonoscopy. 198 were eligible, and after randomization, 90 patients were included across three groups (colonoscopy n = 30, CADe n = 30, CADe + ECV = 30). The ADR was higher in the CADe + ECV group compared to the CADe and colonoscopy groups: 60% versus 40%, and 30%, respectively (p = 0.03). The number of polyps ⩽3 mm detected was greater in the CADe + ECV group (n = 23) versus CADe (n = 7) and colonoscopy (n = 12) groups, respectively (p = 0.03). CADe + ECV identified more polyps in the cecum/right colon (n = 26) compared to CADe (n = 18) and colonoscopy (n = 12) groups (p = 0.04), and in the left colon/sigmoid (n = 14) compared to CADe (n = 5) and colonoscopy (n = 2) (p = 0.02).

Conclusion: These findings underscore the synergic potential of combining CADe with ECV to enhance ADR and enable us to perform sample size calculations for future RCTs.

Registration: Clinical Trials number: NCT05080088. Registration 06/06/2021.

Cirrhotic liver nodules can progress to hepatocellular carcinoma (HCC) through a multi-step carcinogenesis model, with dysplastic nodules being particularly high risk. Currently, monitoring the progression of non-HCC cirrhotic nodules is primarily through dynamic observation, but there is a lack of sensitive, efficient, and convenient methods. Dynamic monitoring and risk evaluation of malignant transformation are essential for timely treatment and improved patient survival rates. Routine liver biopsies are impractical for monitoring, and imaging techniques like ultrasound, computed tomography, and magnetic resonance imaging are not suitable for all patients or for accurately assessing subcentimeter nodules. Identifying serum biomarkers with high sensitivity, specificity, and stability, and developing a multi-index evaluation model, may provide a more convenient and efficient approach to monitoring pathological changes in cirrhotic nodules.

Current therapeutic strategies for inflammatory bowel disease (IBD) have reached a plateau in the rates of response and/or remission achieved with a single therapeutic agent. Consequently, the advanced combination therapy (ACT) strategy has emerged as a novel treatment concept for IBD. ACT involves the use of two different targeted therapies, whether biologic or small molecules, with the primary goal of overcoming the therapeutic plateau. Real-world evidence is accumulating among patients undergoing ACT, especially those dealing with concurrent IBD and extraintestinal manifestations or grappling with medically refractory IBD. The recently conducted VEGA study, a randomized clinical trial, has provided crucial insights by demonstrating that the short-term combination of dual biological agents can lead to superior disease control compared to single agents in patients diagnosed with ulcerative colitis (UC). This suggests that ACT holds promise as a therapeutic option to enhance disease control effectively. However, there is still limited evidence of ACT in UC patients who have proven refractory to biologic therapy and patients with Crohn's disease. This review aims to discuss whether ACT represents the optimal approach for overcoming the therapeutic ceiling in IBD.

Irritable bowel syndrome (IBS) is a common and potentially modifiable contributor to excess disability, morbidity, and poor quality of life. Clinical trials of medications for IBS have largely been in younger adults. Yet, a growing number of adults aged 65 and older are living with IBS. No data exist to guide clinicians in the safe and effective use of medications (e.g., anticholinergics, anti-spasmodics, and tricyclic antidepressants (TCA)) for IBS in the geriatric population. These medications-especially anticholinergics and TCAs-carry a high risk of adverse effects (ADE) in older adults because of age-associated decline in drug metabolism and the high prevalence of multiple chronic conditions. Five or more medications (polypharmacy) are frequently used to treat common psychiatric and medical comorbidities of IBS: anxiety, depression, insomnia, migraine headache, diarrhea, nausea, poor appetite, pruritus/skin atopy, and fibromyalgia. These neurological and psychiatric comorbidities reflect shared pathogenic mechanisms and bidirectional crosstalk of high inflammation, alteration of gut microbiota, and dysregulation of multiple gastrointestinal and central nervous system-active neurotransmitters (e.g., serotonin, neuropeptides). Currently, these IBS-associated conditions are treated with multiple medications-which increase the risk of adverse drug-drug interactions. One way to reduce the number of medications used for IBS-associated conditions is the use of one medication that treats many or all of these conditions-Mirtazapine. In this perspective article, we present evidence from basic science, case series, observational and epidemiological studies, clinical studies, and clinical trials supporting mirtazapine, a noradrenergic and specific serotonergic receptor antagonist-with 5-hydroxytryptamine-2 and 3 antagonism, as a potential pharmacotherapeutic intervention for the myriad symptoms and conditions associated with IBS. Specifically, we found evidence of mirtazapine's role in treating diarrhea, insomnia, migraine headache, nausea, and poor appetite. We propose a large randomized controlled trial to study mirtazapine as a potential one-stop treatment for multiple IBS symptoms, with the potential to reduce polypharmacy and ADEs, especially in the geriatric population.

Background: The diagnostic accuracy of colon capsule endoscopy (CCE) depends on a well-cleansed bowel. Evaluating the cleansing quality can be difficult with a substantial interobserver variation.

Objectives: Our primary aim was to establish a standard of agreement for bowel cleansing in CCE based on evaluations by expert readers. Then, we aimed to investigate the interobserver agreement on bowel cleansing.

Design: We conducted an interobserver agreement study on bowel cleansing quality.

Methods: Readers with different experience levels in CCE and colonoscopy evaluated bowel cleansing quality on the Leighton-Rex scale and Colon Capsule CLEansing Assessment and Report (CC-CLEAR), respectively. All evaluations were reported on an image level. A total of 24 readers rated 500 images on each scale.

Results: An expert opinion-based agreement standard could be set for poor and excellent cleansing but not for the spectrum in between, as the experts agreed on only a limited number of images representing fair and good cleansing. The overall interobserver agreement on the Leighton-Rex full scale was good (intraclass correlation coefficient (ICC) 0.84, 95% CI (0.82-0.85)) and remained good when stratified by experience level. On the full CC-CLEAR scale, the overall agreement was moderate (ICC 0.62, 95% CI (0.59-0.65)) and remained so when stratified by experience level.

Conclusion: The interobserver agreement was good for the Leighton-Rex scale and moderate for CC-CLEAR, irrespective of the reader's experience level. It was not possible to establish an expert-opinion standard of agreement for cleansing quality in CCE images. Dedicated training in using the scales may improve agreement and enable future algorithm calibration for artificial intelligence supported cleansing evaluation.

Trial registration: All included images were derived from the CAREforCOLON 2015 trial (Registered with The Regional Health Research Ethics Committee (Registration number: S-20190100), the Danish data protection agency (Ref. 19/29858), and ClinicalTrials.gov (registration number: NCT04049357)).

The gap between endoscopy and histology is getting closer with the introduction of sophisticated endoscopic technologies. Furthermore, unprecedented advances in artificial intelligence (AI) have enabled objective assessment of endoscopy and digital pathology, providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity. These advancements result in improved disease management by predicting treatment response and long-term outcomes. AI will also support endoscopy in raising the standard of clinical trial study design by facilitating patient recruitment and improving the validity of endoscopic readings and endoscopy quality, thus overcoming the subjective variability in scoring. Accordingly, AI will be an ideal adjunct tool for enhancing, complementing, and improving our understanding of ulcerative colitis course. This review explores promising AI applications enabled by endoscopy and histology techniques. We further discuss future directions, envisioning a bright future where AI technology extends the frontiers beyond human limits and boundaries.