Comprehensive overview of novel chemical drugs for ulcerative colitis: focusing on phase 3 and beyond.

INTRODUCTION: Despite the growing number of highly efficacious biologics and chemical drugs for ulcerative colitis (UC), steroid-free disease control is still difficult to achieve in subgroups of patients due to refractoriness, adverse events, primary or secondary failure. New treatments are therefore still required in order to optimize clinical management of patients with UC. AREAS COVERED: The efficacy and safety of both currently available and newly developed small molecules have been summarized. The PubMed database and clinicaltrials.gov were considered in order to search for phase 2b and 3 trials on new chemical drugs for UC. The study drugs reviewed included Janus kinases (JAK) and sphingosine-1-phosphate receptor (S1Pr) inhibitors, α4 integrin antagonist, and micro-RNA-124 upregulators. EXPERT OPINION: Rapidity of onset, low immunogenicity, and safety are the main characteristics of small molecules currently available or under evaluation for treatment patients with UC. Among the currently available chemical drugs, the selective JAK and the S1Pr inhibitors are characterized by a good safety profile combined with the ability to induce clinical remission in UC. A relatively low frequency of endoscopic improvement and healing currently appears associated with their use, being higher in UC patients treated with S1Pr inhibitor Etrasimod. Overall, additional new safe and effective drugs are still required in order to optimize disease control in a larger majority of UC patients.

Mucinous and Signet-Ring Cell Colonic Adenocarcinoma in Inflammatory Bowel Disease: A Case-Control Study.

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

Severe acute respiratory syndrome coronavirus 2 infection does not worsen the course of inflammatory bowel disease in the long term.

BACKGROUND: The long-term outcome of inflammatory bowel disease (IBD) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is under investigation. AIM: To assess, in a prospective study, whether a recent SARS-CoV-2 infection increases the risk of IBD relapse within 12 months. METHODS: From March to April 2021, all IBD patients with recent (<2 months) SARS-CoV-2 infection (Cases) were enrolled. For each enrolled Case, four IBD Controls with no history of infection were considered. Clinical course of IBD was recorded for 12 months. Inclusion criteria: well defined diagnosis of IBD; age ≥18 and ≤85 years; 12-month follow-up; consent. Exclusion criteria: incomplete data; SARS-CoV-2 infection after enrollment. Additional inclusion criteria: recent SARS-CoV-2 infection for Cases; no history of SARS-CoV-2 infection for Controls. Data expressed as median [range]. Statistical analysis: Student-t-Test, Mann-Whitney U-test, χ2 test, multivariate logistic regression model [odds ratio (95% confidence interval)], Kaplan-Meier curves. RESULTS: One hundred forty-three IBD patients were enrolled. The analysis included 118 patients (22 met the exclusion criteria, three lost at follow-up): 29 (24.6%) Cases and 89 (75.4%) Controls. Demographic and clinical characteristics were comparable between groups. During the 12-month study, the frequency of IBD relapse was comparable between Cases and Controls [8 (27%) vs 19 (21%); P = 0.65]. At univariate analysis, SARS-CoV-2 infection was not a risk factor for IBD relapse within 12 months [1.5 (0.6-3.9); P = 0.34]. At multivariate analysis, IBD activity at baseline was the only risk factor for relapse [3.2 (1.1-9.1); P = 0.03]. Kaplan-Meier curves showed that survival from IBD relapse was comparable between Cases and Controls (P = 0.33). CONCLUSION: In a prospective 12-month study, a recent SARS-CoV-2 infection did not increase the risk of clinical relapse of IBD in the long term.

High Frequency of Deep Infiltrating Endometriosis in Patients with Inflammatory Bowel Disease: A Nested Case-Control Study.

INTRODUCTION: Inflammatory bowel disease (IBD) and endometriosis are chronic inflammatory diseases occurring in young women, sharing some clinical manifestations. In a multidisciplinary approach, we aimed to investigate symptoms, type, and site of pelvic endometriosis in IBD patients versus non-IBD controls with endometriosis. METHODS: In a prospective nested case-control study, all female premenopausal IBD patients showing symptoms compatible with endometriosis were enrolled. Patients were referred to dedicated gynecologists for assessing pelvic endometriosis by transvaginal sonography (TVS). Each IBD patient with endometriosis (cases) was retrospectively matched for age (±5 years) and body mass index (±1) with 4 patients with endometriosis at TVS but no-IBD (controls). Data were expressed as median [range]; the Mann-Whitney or Student t and χ2 tests were used for comparisons. RESULTS: Endometriosis was diagnosed in 25 (71%) out of 35 IBD patients with compatible symptoms including 12 (52.6%) Crohn's disease and 13 (47.4%) ulcerative colitis patients. Dyspareunia and dyschezia were significantly more frequent in cases versus controls (25 [73.7%] vs. 26 [45.6%]; p = 0.03). At TVS, deep infiltrating endometriosis (DIE) and posterior adenomyosis were significantly more frequently observed in cases versus controls (25 [100%] vs. 80 [80%]; p = 0.03 and 19 [76%] vs. 48 [48%]; p = 0.02). CONCLUSIONS: Endometriosis was detected in two-thirds of IBD patients with compatible symptoms. The frequency of DIE and posterior adenomyosis was higher in IBD than in controls. A diagnosis of endometriosis, often mimicking IBD activity, should be considered in subgroups of female patients with IBD.