Low Body Mass Index Can Identify Majority of Osteoporotic Inflammatory Bowel Disease Patients Missed by Current Guidelines

Background. Patients with inflammatory bowel disease (IBD) are at high risk of developing osteoporosis. Our objective was to determine the usefulness of IBD guidelines in identifying patients at risk for developing osteoporosis. Methods. We utilized institutional repository to identify patients seen in IBD center and extracted data on demographics, disease history, conventional, and nonconventional risk factors for osteoporosis and Dual Energy X-ray Absorptiometry (DXA) findings. Results. 59% of patients (1004/1703) in our IBD cohort had at least one risk factor for osteoporosis screening. DXA was documented in 263 patients with indication of screening (provider adherence, 26.2%), and of these, 196 patients had DXA completed (“at-risk” group). Ninety-five patients not meeting guidelines-based risk factors also had DXA completed (“not at-risk” group). 139 (70.9%) patients in “at-risk” group had low BMD, while 51 (53.7%) of “not-at-risk” patients had low BMD. Majority of the patients with osteoporosis (83.3%) missed by the current guidelines had low BMI. Multivariate logistic regression analysis showed that low BMI was the strongest risk factor for osteoporosis (OR 3.07; 95% CI, 1.47–6.42; P = 0.003). Conclusions. Provider adherence to current guidelines is suboptimal. Low BMI can identify majority of the patients with osteoporosis that are missed by current guidelines

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03183141

Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease

AbstractBackground & Aims: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). Methods: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to Results: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 μg, 18% [9.6–29.2]; 4 μg, 20% [11.3–32.2]; 8 μg, 20% [11.1–31.8]; 20 μg, 28% [18–40.7]; and placebo, 18% [9.6–29.6]). Clinical improvement was observed in 46% (33.7–59) in the 8-μg/kg rhuIL-10 group in comparison with 27% (17–39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-κB p65 activation in contrast to nonresponders. Conclusions: Up to 8 μg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-μg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.GASTROENTEROLOGY 2000;119:1461-147

Motion - Colonoscopic Surveillance is More Cost Effective than Colectomy in Patients with Ulcerative Colitis: Arguments for the Motion

Patients with ulcerative colitis (UC) are at increased risk for colorectal cancer (CRC), especially those with longstanding disease, pancolitis or primary sclerosing cholangitis. The incidence of colitis- associated cancer is increasing, and the mortality rates from CRC are higher in UC patients than in the general population. Case control studies have demonstrated that surveillance colonoscopy reduces the risk of dying from CRC. A well conducted decision analysis found that surveillance colonoscopy decreases cancer-related mortality and increases life expectancy. The results with surveillance programs were almost as good as with prophylactic colectomy. A subsequent cost effectiveness analysis using the same model found that, compared with a policy of no surveillance, colonoscopic surveillance was more effective at preventing death from CRC and was less costly. The best strategy appears to be to perform colonoscopies every three years. The analysis also showed that colectomy should be recommended in patients with low-grade dysplasia. Patients at very high risk for CRC should undergo yearly colonoscopy, and patients who are concerned about the limitations of this technique should be offered prophylactic colectomy