Novel and emerging drugs for the treatment of Crohn's disease: a review of phase II and III trials.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. While several therapeutic options, such as anti-tumor necrosis factor (TNF), anti-integrin, and interleukin (IL) 12/23 inhibitors, as well as IL-23 and Janus kinase (JAK) inhibitors, have been approved for CD treatment, a substantial number of patients fail to respond adequately or experience a loss of response over time. In recent years, the scientific community has been actively investigating novel agents to address these challenges and improve the management of CD. AREAS COVERED: This comprehensive narrative review provides an overview of recent developments in CD treatment, summarizing phase 2 and phase 3 clinical trial data. We delve into the clinical efficacy and safety profiles of emerging therapies, encompassing JAK inhibitors, IL-23 inhibitors, anti-adhesion molecules, S1P1 receptor modulators, and combined targeted treatments. EXPERT OPINION: The armamentarium of CD therapeutic agents is constantly expanding. We analyze pivotal findings from phase 2 and phase 3 CD treatment trials. We also underscore the existing gaps in therapy and the paramount role of ongoing research and innovation in CD management.

Efficacy of prucalopride in critically ill patients with paralytic ileus: A pilot randomized double-blind placebo-controlled trial.

BACKGROUND AND AIM: Paralytic ileus is a common intestinal dysfunction in critically ill patients, which results in complications and poor hospital outcomes. There are still no established effective medications, except correcting the primary causes and prokinetics trial, which have limited efficacy and potential adverse events. This study aims to evaluate the efficacy of prucalopride on paralytic ileus in critically ill patients. METHODS: A randomized, double-blind, placebo-controlled trial of five consecutive days treatment periods was conducted. Critically ill patients with paralytic ileus were included. The primary endpoint was the improvement of bowel dilatation on plain abdominal radiography. The secondary endpoint was the change of abdominal circumference. RESULTS: Twenty patients were consecutively enrolled in the study. There was no significant difference in baseline characteristics of patients. The common causes of hospitalization were infection and respiratory problems. The maximum large bowel diameters dramatically decreased in prucalopride group and reached maximum point on the third day after intervention when compared with placebo (-2.1 [± 1.8] vs 0.3 [± 1.5] cm, P = 0.01). The maximum small bowel diameters were noticeably less decreased and were not significantly different when compared with placebo. The abdominal circumferences notably decreased and significantly diverged from placebo on the third day. CONCLUSIONS: Prucalopride was an effective enterokinetic agent to improve non-severe inflammatory/ischemic bowel conditions related paralytic ileus in critically ill patients. Its effect was predominant on large intestine but could not be well demonstrated on small bowel in this study. Future study or concomitant other prokinetics for upper gut motility should be further evaluated.

Re-bleeding and its predictors after capsule endoscopy in patients with obscure gastrointestinal bleeding in long-term follow-up.

BACKGROUND: Capsule endoscopy (CE) is the preferred diagnostic test of choice in the investigation of obscure gastrointestinal bleeding (OGIB). Although, a conservative strategy is recommended in the short-term, for cases with a negative result from CE, the impact of CE on long-term re-bleeding still remains unclear. Hence, the aim of this study was to determine the long-term re-bleeding rate along with predictors after CE in patients with OGIB. METHODS: We retrospectively reviewed 216 patients with OGIB, whom had received a CE examination, so as to investigate the cause of obscure GI bleeding; between July 2008 and March 2018. The patient's characteristics, medication use, CE finding, treatments strategy, re-bleeding episodes and follow-up information were collected from the institutional electronic medical chart and CE database. Re-bleeding free survival was evaluated using Kaplan-Meier curves with log rank test, whilst predictors associated with the re-bleeding episodes were analyzed via the use of Cox proportional hazard model. RESULTS: One hundred and thirty-three patients with OGIB, having received CE were enrolled in the analysis. The pool rate of re-bleeding was 26.3% (35/133) during a follow-up duration of 26 months after CE. Patients with positive CE study, without specific treatment, had higher rates of re-bleeding (47.6%) than those with positive study whom received specific treatment (25.7%), and negative study (20.8%) (p = 0.042). Although, the re-bleeding free survival was not significantly different among the groups (log rank test; P = 0.10). Re-bleeding events occurring within 6, 12, and 24 months after CE were 36, 64 and 92%, respectively. The high-frequency re-bleeding etiologies were the small bowel angiodysplasias and abnormal vascular lesions. Furthermore, independent predictors for re-bleeding after CE were patients with cirrhosis (hazard ratio, HR 4.06), incomplete CE visualization (HR 2.97), and a history of previous GI bleeding (HR 2.80). CONCLUSIONS: The likelihood of re-bleeding after CE was higher in patients with positive CE study than those with negative study. Specific treatments, or therapeutic interventions for patients with detectable lesions reduced the probability of re-bleeding episodes in long-term follow-up. Close follow-up for recurrent bleeding is recommeded for at least 2 years after CE.

Current Evidence for Combined Targeted Therapy for the Treatment of Inflammatory Bowel Disease.

Biologicals and small molecules have revolutionized the medical management of inflammatory bowel diseases (IBD), yet they are only effective in a proportion of patients, and their impact on changing the natural history of the disease is still debatable. Recently, the concept of combining targeted biologics and small-molecule therapies has been introduced to the treatment of IBD. Dual-targeted therapy (sequential and combined), which is the combination of two targeted therapies, might be a reasonable choice for patients to break through the therapeutic ceiling. A recent randomized clinical trial (VEGA) provided the first controlled evidence that the short-term combination of two biological agents may lead to superior disease control than either of the agents alone in patients with ulcerative colitis (UC) without jeopardizing safety. Multiple studies are underway in both Crohn's disease and UC. Additionally, real-world evidence is accumulating in IBD patients receiving combination therapies with concomitant IBD and extraintestinal manifestations or in patients with medically refractory IBD. Of note, the majority of these patients were exposed to multiple biological agents earlier and lost response to at least one of the agents in the combination. This review summarizes current knowledge regarding this attractive novel therapeutic option in IBD. Clearly, more controlled data are needed to evaluate optimal timing, efficacy, and mitigation of safety concerns.

How close are we to a success stratification tool for improving biological therapy in ulcerative colitis?

INTRODUCTION: Biological therapies have become the standard treatment for ulcerative colitis (UC). However, clinical remission rates post-induction therapy remain modest at 40-50%, with many initial responders losing response over time. Current treatment strategies frequently rely on a 'trial and error' approach, leading to prolonged periods of ineffective and costly therapies for patients, accompanied by associated treatment complications. AREA COVERED: This review discusses current evidence on risk stratification tools for predicting therapeutic efficacy and minimizing adverse events in UC management. Recent studies have identified predictive factors for biologic therapy response. In the context of personalized medicine, the goal is to identify patients at high risk of progression and complications, as well as those likely to respond to specific therapies. Essential risk stratification tools include clinical decision-making aids, biomarkers, genomics, multi-omics factors, endoscopic, imaging, and histological assessments. EXPERT OPINION: Employing risk stratification tools to predict therapeutic response and prevent treatment-related complications is essential for precision medicine in the biological management of UC. These tools are necessary to select the most suitable treatment for each individual patient, thereby enhancing efficacy and safety.

Orbital Metastasis as the First Manifestation of Hepatocellular Carcinoma, and Its Effective Treatment with Combined Dual Immunotherapy: A Case Report and Review of the Literature.

BACKGROUND Orbital metastasis originating from hepatocellular carcinoma (HCC), particularly as an initial manifestation in patients without a known history of HCC, is rare. Few reports exist on the treatment of patients having HCC with orbital metastasis using targeted therapy or immunotherapy. CASE REPORT We report a case of advanced-stage HCC in a 65-year-old man who first presented with progressive, painless blurred vision and proptosis of the right eye for 2 weeks. The patient had no history of chronic liver disease or cancer. Computed tomography revealed an enhancing hyperdense extraconal mass in the right orbit; a biopsy revealed metastatic HCC. Abdominal CT, which was performed to investigate the primary cancer, revealed a 1.2×1.6-cm arterial-enhancing nodule with venous washout in hepatic segment 5, associated with liver cirrhosis. The patient's serum alpha-fetoprotein level was 70.27 ng/dL. Chest computed tomography revealed lung metastasis. Thus, first-line systemic therapy combining durvalumab and tremelimumab was initiated alongside palliative radiotherapy targeting the right orbit, which began 1 week after the first dose of dual immunotherapy. The patient had significant clinical improvement, reduced proptosis, and serum alpha-fetoprotein levels. CONCLUSIONS Although orbital metastasis is a rare manifestation of HCC, physicians should recognize and consider aggressive investigations for early diagnosis, especially in patients with existing risk factors for HCC. Dual immunotherapy with durvalumab and tremelimumab in combination with radiotherapy can be considered a potential treatment option for managing advanced HCC with orbital metastasis.

Comparing the Efficacy of Carboplatin plus 5-Fluorouracil, Cisplatin plus 5-Fluorouracil, and Best Supportive Care for Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score Analysis from a Tertiary Hospital in Southern Thailand.

Background: Although cisplatin plus 5-fluorouracil (5-FU) is the standard first-line treatment for advanced-stage esophageal squamous cell carcinoma (ESCC), carboplatin was substituted for cisplatin in cisplatin-ineligible patients. The efficacy of carboplatin plus 5-FU for advanced-stage ESCC remains unreported. Methods: This retrospective study analyzed first-line treatment-carboplatin plus 5-FU, cisplatin plus 5-FU, or best supportive care (BSC)-in advanced-stage ESCC patients at a tertiary hospital in Thailand (2012-2022). Survival was assessed using the Kaplan-Meier method, compared via the log-rank test, and adjusted through propensity score matching. Significance was set at p < 0.05. Results: Of 256 patients, 39.9% received carboplatin plus 5-FU, 27.7% cisplatin plus 5-FU, and 32.4% BSC. Carboplatin was significantly associated with older age, poorer performance status, more comorbidities, chronic kidney disease, and lower creatinine clearance. Median overall survival (OS) for carboplatin plus 5-FU, cisplatin plus 5-FU, and BSC was 8.05 (HR 0.31 [0.23, 0.43] vs. BSC, p < 0.001; HR 1.06 [0.78, 1.44] vs. cisplatin plus 5-FU, p = 0.7), 8.43, and 3.64 months, respectively. No significant OS difference was observed between carboplatin and cisplatin treatments after propensity score matching. Median progression-free survival (PFS) and objective response rates (ORR) showed no significant difference between carboplatin and cisplatin treatments. Conclusions: Despite less favorable baseline characteristics of patients receiving carboplatin plus 5-FU, this combination exhibited comparable OS, PFS, and ORR to cisplatin plus 5-FU in real-world scenarios. Furthermore, it significantly improved OS over BSC. Consequently, carboplatin plus 5-FU should be considered as an alternative regimen, particularly for advanced-stage ESCC patients who are ineligible for cisplatin.

Clinical efficacy and nocebo effect following non-medical biosimilar switch in patients with inflammatory bowel disease: A prospective observational study.

BACKGROUND: We aimed to evaluate clinical efficacy, biomarker activity, therapeutic drug monitoring (TDM), adverse events (AEs), and nocebo effect in inflammatory bowel disease (IBD) patients who underwent non-medical biosimilar switching. METHODS: A prospective observational study of consecutive IBD patients who underwent biosimilar switch. Disease activity, biomarkers, TDM, and AEs, including the nocebo effect were captured 8 weeks before switch, at the time of switch (baseline),12 and 24 weeks after the switch. RESULTS: 210 patients were included [81.4% had Crohn's disease (CD), the median age at inclusion: 42 years (IQR 29-61)]. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week12, and 24 after switch: 89.0%,93.4%,86.3%,and 90.8%,p = 0.129. The biomarker remission rates were not significantly different; CRP:81.3%,74.7%,81.2%,73.0%,p = 0.343; fecal calprotectin: 78.3%,74.5%,71.7%,76.3%,p = 0.829. The rates of maintaining therapeutic levels (84.7%,83.9%,83.0%,85.3%,p = 0.597) and prevalence of positive anti-drug antibodies remained unchanged. Drug persistence at 12 week of switch was 97.1%, regardless of disease phenotype and originator. The nocebo effect was observed in 13.3%. The discontinuation rate was 4.8%. CONCLUSION: Despite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, or anti-drug antibodies.

Efficacy of Vonoprazan vs. Intravenous Proton Pump Inhibitor in Prevention of Re-Bleeding of High-Risk Peptic Ulcers: A Randomized Controlled Pilot Study.

Background: Proton pump inhibitor (PPI) therapy is well-established for its effectiveness in reducing re-bleeding in high-risk peptic ulcer patients following endoscopic hemostasis. Vonoprazan (VPZ) has demonstrated the capacity to achieve gastric pH levels exceeding 4, comparable to PPIs. This study aims to evaluate the comparative efficacy of intravenous PPI infusion versus VPZ in preventing re-bleeding after endoscopic hemostasis in patients with high-risk peptic ulcers. Methods: A randomized, double-blind, controlled, and double-dummy design was employed. Patients with peptic ulcer bleeding (Forrest class IA/IB or IIA/IIB) who underwent endoscopic hemostasis were randomly assigned to either the PPI group or the VPZ group. Re-bleeding rates at 3, 7, and 30 days, the number of blood transfusions required, length of hospitalization, and ulcer healing rate at 56 days were assessed. Results: A total of 44 eligible patients were enrolled, including 20 patients (PPI group, n = 11; VPZ group, n = 9) with high-risk peptic ulcers. The mean age was 66 years, with 70% being male. Re-bleeding within 72 h occurred in 9.1% of the PPI group versus 0% in the VPZ group (p = 1.000). There was no significant difference in re-bleeding rates within 7 days and 30 days (18.2% vs. 11.1%, p = 1.000). Additionally, the ulcer healing rate did not significantly differ between the groups (87.5% vs. 77.8%). Conclusions: This pilot study demonstrates comparable efficacy between oral vonoprazan and continuous PPI infusion in preventing recurrent bleeding events among high-risk peptic ulcer patients following successful endoscopic hemostasis.

Accuracy of the Pancolonic Modified Mayo Score in predicting the long-term outcomes of ulcerative colitis: a promising scoring system.

Background: Different endoscopic scoring systems for assessing ulcerative colitis (UC) severity are available. However, most of them are not correlated with disease extent. Objectives: Our study aimed to compare the predictive value of the PanMay score versus the endoscopic Mayo (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Dublin score in predicting long-term outcomes of UC. Design: This retrospective study enrolled consecutive UC patients who underwent colonoscopy before at least a 3-year follow-up. Methods: The PanMayo, MES, UCEIS, and Dublin scores and the baseline clinical and demographic characteristics of the participants were assessed. Endpoints were disease flare that required novel biological therapy, colectomy, and hospitalization. Patients were stratified using baseline clinical activity. Results: Approximately 62.8% of the 250 enrolled patients were in clinical remission. In these patients, the PanMayo, MES, and Dublin scores were positively associated with the risk of clinical flare. The MES score increased with clinical flare. The PanMayo score (>12 points), but not the MES score, was associated with the need for novel biological initiation and biological escalation. Furthermore, the Dublin and UCEIS scores of patients in remission who need novel biological treatment had a similar trend. Colectomy risk was associated with PanMayo and Dublin scores. Conclusion: The combined endoscopic assessment of disease extent and severity can be more accurate in predicting outcomes among patients with UC. PanMayo score can be utilized in addition to the existing scoring systems, thereby leading to a more accurate examination. Summary: UC endoscopic scores do not assess extension. Our study aimed to analyze the predictive value of the PanMayo score. Based on 250 patients, results showed that the long-term disease outcomes of UC could be predicted with the PanMayo score more accurately.

Monitoring of Inflammatory Bowel Disease in Pregnancy: A Review of the Different Modalities.

Inflammatory Bowel Disease (IBD) significantly affects women in their reproductive years. Understanding the relationship between IBD and pregnancy is crucial, given its impact across pre-gestational, gestational, and postpartum phases. Monitoring IBD activity during pregnancy involves various modalities. This review discusses these modalities, focusing on the efficacy and safety of Small Intestine Ultrasound (IUS) as a noninvasive and reliable option. While IUS has gained popularity, its technique-sensitive nature necessitates trained staff for optimal usage.

The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer.

Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.

FAIL-T (AFP, AST, tumor sIze, ALT, and Tumor number): a model to predict intermediate-stage HCC patients who are not good candidates for TACE.

Background: Patients with un-resectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) are a diverse group with varying overall survival (OS). Despite the availability of several scoring systems for predicting OS, one of the unsolved problems is identifying patients who might not benefit from TACE. We aim to develop and validate a model for identifying HCC patients who would survive <6 months after their first TACE. Methods: Patients with un-resectable HCC, BCLC stage 0-B, who received TACE as their first and only treatment between 2007 and 2020 were included in this study. Before the first TACE, demographic data, laboratory data, and tumor characteristics were obtained. Eligible patients were randomly allocated in a 2:1 ratio to training and validation sets. The former was used for model development using stepwise multivariate logistic regression, and the model was validated in the latter set. Results: A total of 317 patients were included in the study (210 for the training set and 107 for the validation set). The baseline characteristics of the two sets were comparable. The final model (FAIL-T) included AFP, AST, tumor sIze, ALT, and Tumor number. The FAIL-T model yielded AUROCs of 0.855 and 0.806 for predicting 6-month mortality after TACE in the training and validation sets, respectively, while the "six-and-twelve" score showed AUROCs of 0.751 (P < 0.001) in the training set and 0.729 (P = 0.099) in the validation sets for the same purpose. Conclusion: The final model is useful for predicting 6-month mortality in naive HCC patients undergoing TACE. HCC patients with high FAIL-T scores may not benefit from TACE, and other treatment options, if available, should be considered.

Long-term Colectomy Rates of Ulcerative Colitis over 40 Years of Different Therapeutic Eras-Results from a Western Hungarian Population-based Inception Cohort Between 1977 and 2020.

BACKGROUND AND AIMS: Few populaion-based studies have investigated the long-term colectomy rates of ulcerative colitis [UC]. We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary. METHODS: Patient inclusion lasted between January1, 1977, and December31, 2018. Patient follow-up ended December 31, 2020. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort A [1977-1995], cohort B [1996-2008], and cohort C [2009-2018]. RESULTS: A total of 1370 incident UC patients were included [male 51.2%, median age at diagnosis 37 years]. Median follow-up was 17 years (interquartile range [IQR] 9-24); 87 patients [6.4%] underwent colectomy. The cumulative probability of colectomy in the total population was 2.6% (95% confidence interval [CI] 2.2-3.0), 4.2% [95% CI 3.6-4.8], 7.0% [95% CI 6.2-7.8], and 10.4% [95% CI 9.1-11.7] after 5, 10, 20, and 30 years, respectively. The proportion of extensive colitis at diagnosis increased over time [24.2%/24.3%/34.9% in cohorts A/B/C, respectively, p = 0.001]. Overall exposure to immunomodulators [11.3%/20.9%/34.4% in cohorts A/B/C, respectively, p <0.001], as well as the probability for biologic therapy initiation increased over time (0%/3.3% [95% CI 2.6-4.0]/13.9% [95% CI 12.1-15.7], p <0.001). There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C: 1.7% [95% CI 1.0-2.4], 2.5% [95% CI 1.9-3.1], and 3.7% [95% CI 2.7-4.7] after 5 years; 3.5% [95% CI 2.5-4.5], 4.2% [95% CI 3.4-5.0], and 4.5% [95% CI 3.3-5.7] after 10 years; and 7.5% [95% CI 6.1-8.9] and 6.3% [95% CI 5.2-7.4] in cohorts A/B after 20 years [log-rank = 0.588]. Extensive colitis (hazard ratio [HR] 2.24, 95% CI 1.55-3.23) and continuous active disease activity [HR 6.36, 95% CI 3.46-11.67] were independent predictors for colectomy. CONCLUSION: No differences in colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biologic therapies.

Time Trends of Environmental and Socioeconomic Risk Factors in Patients with Inflammatory Bowel Disease over 40 Years: A Population-Based Inception Cohort 1977-2020.

BACKGROUND: Data from population-based studies investigating trends in environmental factors associated with inflammatory bowel disease (IBD) is lacking. We aimed to assess long-term time trends of environmental and socioeconomic factors in IBD patients from a well-defined population-based cohort from Veszprem, Hungary. METHODS: Patients were included between 1 January 1977, and 31 December 2020. Trends of environmental and socioeconomic factors were evaluated in three periods based on the decade of diagnosis, representing different therapeutic eras: cohort-A,1977-1995; cohort-B,1996-2008 (immunomodulator era); and cohort-C, 2009-2020 (biological era). RESULTS: A total of 2240 incident patients with IBD were included (ulcerative colitis (UC) 61.2%, male 51.2%, median age at diagnosis: 35 years (IQR 29-49)). Rates of active smoking significantly decreased over time in Crohn's disease (CD): 60.2%, 49.9%, and 38.6% in cohorts A/B/C (p < 0.001). In UC, the rates were low and stable: 15.4%, 15.4%, and 14.5% in cohorts A/B/C (p = 0.981). Oral contraceptive use was more common in CD compared to UC (25.0% vs. 11.6%, p < 0.001). In UC, prevalence of appendectomy before diagnosis decreased over time: 6.4%, 5.5%, and 2.3% in cohorts A/B/C (p = 0.013). No significant changes were found in the socio-geographic characteristics of the IBD population (urban living: UC, 59.8%/64.8%/ 62.5% (p = 0.309) and CD, 62.5%/ 62.0%/ 59.0% (p = 0.636), in cohorts A/B/C). A greater percentage of patients had completed secondary school as the highest education level in later cohorts in both UC (42.9%/50.2%/51.6%, p < 0.001) and CD (49.2%/51.7%/59.5%, p = 0.002). A higher percentage of skilled workers (34.4%/36.2%/38.9%, p = 0.027) was found in UC, but not in CD (p = 0.454). CONCLUSION: The association between trends of known environmental factors and IBD is complex. Smoking has become less prevalent in CD, but no other major changes occurred in socioeconomic factors over the last four decades that could explain the sharp increase in IBD incidence.

Mucosal Healing and Clinical Efficacy of Adalimumab in Small Intestinal Crohn's Disease (SIMCHA Study): Final Results From a Prospective, Open-Label, Single-Arm Study.

BACKGROUND: Endoscopic healing is a key treatment target in inflammatory bowel disease; few data are available on the clinical and endoscopic efficacy of biological therapy in upper gastrointestinal Crohn's disease. This study aimed to investigate small bowel mucosal healing and clinical efficacy of adalimumab therapy by video capsule endoscopy in patients with endoscopically active upper gastrointestinal Crohn's disease. METHODS: This prospective, open-label, single-arm study included Crohn's disease patients with moderate-severe endoscopic proximal small bowel involvement, defined by a Lewis score >790. Patients were treated with adalimumab monotherapy for 24 weeks. Co-primary outcomes were endoscopic healing, defined as Lewis score <350, and endoscopic response, defined as >50% decrease in Lewis score. Secondary outcomes included clinical (Harvey-Bradshaw index <4) and biomarker remission (fecal calprotectin <250 µg/g, and C-reactive protein <5 mg/L). RESULTS: A total of 59 Crohn's disease patients were screened; 17 patients have met eligibility criteria and were enrolled. Endoscopic healing was observed in 8 patients (47.1%) and endoscopic response in additional 5 patients (29.4%) at 24 weeks. Median Lewis score was significantly decreased compared to baseline (1912 vs. 337, P = .0005). Eleven of 13 patients (84.6%) with clinical activity achieved clinical remission (baseline: 13/17 vs. week 24: 2/17, P < .0001). Nine of 10 patients with elevated C-reactive protein achieved normal C-reactive protein after treatment and the median C-reactive protein significantly decreased from 7.4 to 1.6 mg/L, P = .032. In contrast, no change was observed in fecal calprotectin pre- and posttreatment. CONCLUSIONS: Adalimumab induced endoscopic healing and clinical remission in patients with active small bowel Crohn's disease, with approximately half of the patients achieving endoscopic healing.

Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

The effect of fiber supplementation on the prevention of diarrhea in hospitalized patients receiving enteral nutrition: A meta-analysis of randomized controlled trials with the GRADE assessment.

Introduction: Enteral nutrition (EN) in hospitalized patients has several advantages. However, post-feeding diarrhea occurs frequently and has been linked to negative outcomes. The EN formula itself may have an impact on how diarrhea develops, and fiber supplements may theoretically help patients experience less diarrhea. This study aimed to thoroughly evaluate whether adding fiber to EN decreases the likelihood of developing diarrhea and whether different types of fibers pose different effects on diarrhea (PROSPERO CRD 42021279971). Methods: We conducted a meta-analysis on fiber supplementation in hospitalized adult patients receiving EN. We thoroughly searched PubMed, Medline, Embase, Scopus, Web of Science, CENTRAL, and ClinicalTrials.gov databases from inception to 1 September 2022. Only randomized controlled trials (RCTs) were included. Pooled results on the incidence of diarrhea were calculated using a random-effects model. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was applied. Only fiber types from soy polysaccharides (n = 4), psyllium (n = 3), mixed soluble/insoluble fiber (mixed fiber, n = 3), pectin (n = 2), and partially hydrolyzed guar gum (PHGG, n = 2) were examined in the sensitivity analysis. Results: Among the 4,469 titles found, a total of 16 RCTs were included. Overall, compared to fiber-free formulas, fiber supplementation reduced the occurrence of diarrhea in patients receiving EN by 36% (pooled risk ratio [RR] of 0.64 [95% confidence interval (CI): 0.49-0.82, p = 0.005; I 2 = 45%]), with GRADE showing the evidence of moderate certainty. Only mixed fiber and PHGG significantly decreased the incidence of diarrhea according to the sensitivity analyses for fiber types (RR 0.54, 95%CI: 0.39-0.75, I 2 = 0% and RR 0.47, 95%CI: 0.27-0.83, I 2 = 0%, respectively). The results for the remaining fiber types were unclear. Conclusion: According to a meta-analysis, fiber supplements help lessen post-feeding diarrhea in hospitalized patients receiving EN. However, not all fiber types produced successful outcomes. Diarrhea was significantly reduced by PHGG and mixed soluble/insoluble fiber. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=279971, identifier: PROSPERO CRD 42021279971.

The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials.

Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.