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INTRODUCTION: Microscopic colitis (MC) is an inflammatory condition of the large intestine. Primarily diagnosed in middle-aged and older adults, the incidence of the disease has increased markedly during the past few decades. While MC is associated with a reduced quality of life, large-scale studies on the association with future psychiatric disorders are lacking. METHODS: We conducted a nationwide matched cohort study in Sweden from 2006 to 2021. Through a nationwide histopathology database (the Epidemiology Strengthened by histoPathology Reports in Sweden study), we identified 5,816 patients with a colorectal biopsy consistent with MC. These patients were matched with 21,509 reference individuals from the general population all of whom with no previous record of psychiatric disorders. RESULTS: From 2006 to 2021, 519 patients with MC (median age 64.4 years [interquartile range = 49.5-73.3]) and 1,313 reference individuals were diagnosed with psychiatric disorders (9.9 vs 6.5 events per 1,000 person-years), corresponding to 1 extra case of psychiatric disorder in 29 patients with MC over 10 years. After adjustments, the hazard ratio for psychiatric disorders was 1.57 (95% confidence interval = 1.42-1.74). We found significantly elevated estimates up to 10 years after MC diagnosis and a trend toward higher risk with increasing age. Specifically, we observed increased risks for unipolar depression, anxiety disorders, stress-related disorders, substance abuse, and suicide attempts. In sibling-controlled analysis, the adjusted hazard ratio was 1.76 (95% confidence interval = 1.44-2.15). DISCUSSION: Patients with MC are at increased risk of incident psychiatric disorders compared with the general population.
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Endoscopic retrograde cholangiopancreatography-guided transpapillary gallbladder drainage has emerged as an effective alternative for management of acute cholecystitis in nonoperable candidates. Delayed acute pancreatitis has not been previously described as an adverse event with this procedure. In this article, we describe 3 patients who developed acute pancreatitis between 2 and 6 weeks after stent insertion with no alternative inciting cause. Delayed acute pancreatitis may represent a rare and previously uncharacterized adverse event related to transpapillary gallbladder drainage.
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INTRODUCTION: Bile acid sequestrants (BAS) are an option for microscopic colitis (MC) refractory or intolerant to budesonide. There are inconsistent data on the prevalence of bile acid malabsorption (BAM) and utility of bile acid testing in MC. The aim of this systematic review and meta-analysis was to evaluate these outcomes. METHODS: A systematic search of randomized control trials and observational studies of adults with MC treated with BAS was conducted using MEDLINE, Embase, Cochrane, and Scopus from inception to January 22, 2024. Data were extracted on (i) prevalence of BAM, (ii) clinical response and adverse events, and (iii) recurrence after BAS discontinuation. Data were pooled using random-effects models to determine weighted pooled estimates and 95% confidence intervals (CIs). RESULTS: We included 23 studies (1 randomized control trial, 22 observational), with 1,011 patients with MC assessed for BAM and 771 treated with BAS. The pooled prevalence of BAM was 34% (95% CI 0.26-0.42, I2 = 81%). The pooled response rate with BAS induction for all patients with MC, irrespective of BAM, was 62% (95% CI 0.55-0.70, I2 = 71%). There was a higher pooled response rate in patients with BAM compared with those without BAM ( P < 0.0001). The pooled rate of BAS-related adverse effects was 9% (95% CI 0.05-0.14, I2 = 58%). DISCUSSION: One-third of patients with MC had BAM, and almost two-thirds of all patients responded to BAS with limited side effects. Patients with MC and BAM were more likely to respond to therapy, supporting the value of bile acid testing.
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INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.
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Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥ 60 years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected.
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Colitis, Microscopic , Colitis, Ulcerative , Humans , Aged , Quality of Life , Colitis, Microscopic/diagnosis , Colitis, Microscopic/drug therapy , Colitis, Microscopic/epidemiology , Colonoscopy/adverse effects , DiarrheaABSTRACT
BACKGROUND: Tumor necrosis factor (TNF-α) inhibitors and the α4ß7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis. AIMS: To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis. METHODS: Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages. RESULTS: A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I2=43% P=0.08], 57.8% [95% CI (0.3895; 0.7571), I2=0%, P=0.7541], and 39.3% [95% CI (0.0814; 0.7492), I2=66%, P=0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I2=67%, P=0.02], 45.3% [95% CI (0.1479; 0.7747), I2=0%, P=0.36] and 32.5% [95% CI (0.000; 0.8508), I2=53%, P=0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. CONCLUSION: Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life.
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BACKGROUND: Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings. METHODS: A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic. RESULTS: We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2â =â 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9). CONCLUSIONS: Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects.
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We performed an updated study to investigate the rates of urinary tract infections (UTIs) in patients with recurrent Clostridioides difficile infection (CDI) who received fecal microbiota transplantation (FMT) for CDI. We found a significant reduction in number of UTIs after FMT compared to patients who received antibiotics for CDI treatment. After FMT, we also observed a trend towards reduction of antibiotic resistance in organisms causing UTI.
Subject(s)
Clostridioides difficile , Clostridium Infections , Urinary Tract Infections , Humans , Fecal Microbiota Transplantation/adverse effects , Treatment Outcome , Recurrence , Clostridium Infections/microbiology , Urinary Tract Infections/therapy , Urinary Tract Infections/etiologyABSTRACT
BACKGROUND AND AIM: Although fidaxomicin is an effective first-line treatment for Clostridioides difficile infection, it has not been well studied in patients with inflammatory bowel disease. We aimed to assess the effectiveness of fidaxomicin for the treatment of C. difficile infection in patients with inflammatory bowel disease. METHODS: This was a multicenter retrospective study of adults with inflammatory bowel disease and C. difficile infection treated with fidaxomicin with at least 3 months of follow up. The primary outcomes were treatment response, defined as resolution of C. difficile infection-attributed diarrhea and/or negative C. difficile infection stool test, and time to C. difficile infection recurrence after fidaxomicin. RESULTS: Thirty-three patients (median age 42 years; 60.6% female) were included. Most patients had ulcerative colitis (26, 78.8%), were receiving treatment with a biologic or small molecule medication (19, 57.6%), and had a prior episode of C. difficile infection (26, 78.8%, median 2 episodes, range 0-15). Fidaxomicin led to resolution of C. difficile infection in 20 (60.6%) patients, with 6/20 (30.0%) developing a recurrence at a median of 55 days. Most patients who failed to respond to fidaxomicin underwent fecal microbiota transplantation (10/13, 76.9%) with resolution. CONCLUSIONS: In this cohort of patients with inflammatory bowel disease and C. difficile infection, 60.6% responded to treatment with fidaxomicin. Of those who did not respond, fecal microbiota transplantation was an effective therapy.
Subject(s)
Clostridioides difficile , Clostridium Infections , Inflammatory Bowel Diseases , Adult , Humans , Female , Male , Fidaxomicin , Anti-Bacterial Agents , Vancomycin , Retrospective Studies , Clostridium Infections/drug therapy , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Recurrence , Treatment OutcomeABSTRACT
Background: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower. Objectives: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs). Design: A systematic review and meta-analysis was conducted. Data Sources and Methods: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs). Results: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71-85%). There was significant heterogeneity among studies with an I2 of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60-82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p < 0.0001). Conclusions: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies.
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Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available. Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes. Design: Retrospective cohort study. Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996-February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar's test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p < 0.05 was considered statistically significant. Results: Overall, 101 cases and 100 controls (1997-2018) were included; median age 27 (range, 20-41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% (n = 16), during pregnancy: 51.5% (n = 52), and postpartum: 32.7% (n = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery (p = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization (p = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19-543.19; p = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04-0.99; p = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes. Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed.
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Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment. Objectives: We aimed to assess histological changes over time. Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic. Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models. Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34-3.31, p = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34-3.02, p = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16-3.00, p = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19-0.83, p = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14-0.42, p < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47-1.05, p = 0.084). Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide.
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BACKGROUND & AIMS: Bile acid sequestrants (BAS) may be a treatment in microscopic colitis (MC), but efficacy data are limited. We evaluated the effectiveness of BAS in MC and assessed the utility of bile acid testing to predict response. METHODS: Adults with MC treated with BAS (2010-2020) at Mayo Clinic were identified. Bile acid malabsorption was defined by elevated serum 7âº-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs. Response was defined at 12 ± 4 weeks after BAS initiation as: complete (resolution of diarrhea), partial (≥50% improvement in diarrhea), nonresponse (<50% improvement), and intolerance (discontinuation due to side effects). Logistic regression was used to identify predictors of response to BAS. RESULTS: We identified 282 patients (median age, 59 years [range, 20-87 years]; 88.3% women) with median follow-up of 4.5 years (range, 0.4-9.1 years). Patients were treated with the following BAS: 64.9% cholestyramine, 21.6% colesevelam, and 13.5% colestipol. Clinical outcomes were: 49.3% complete response, 16.3% partial response, 24.8% nonresponse, and 9.6% intolerance. There were no differences in outcomes between those on BAS alone or BAS combined with other medications (P = .98). The dose of BAS was not associated with response (P = .51). Bile acid testing was done in 31.9% of patients, and 56.7% were positive. No predictors of response to BAS were identified. After BAS discontinuation, 41.6% had recurrence at a median of 21 weeks (range, 1-172 weeks). CONCLUSION: In one of the largest cohorts evaluating BAS treatment in MC, nearly two-thirds had a partial or complete response. Additional research is needed to determine the role of BAS and bile acid malabsorption in MC.
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Bile Acids and Salts , Colitis, Microscopic , Adult , Humans , Female , Middle Aged , Male , Cholestyramine Resin/therapeutic use , Diarrhea/drug therapy , Colitis, Microscopic/diagnosis , Colitis, Microscopic/drug therapy , Colestipol/therapeutic useABSTRACT
Importance: The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown. Objective: To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial. Design, Setting, and Participants: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote [>6 months earlier] CDI history). Interventions: Participants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days. Main Outcomes and Measures: The primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic. Results: Baseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo). Conclusions and Relevance: Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03788434.
Subject(s)
Clostridioides difficile , Clostridium Infections , Probiotics , Adult , Female , Humans , Male , Middle Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Clostridium Infections/complications , Clostridium Infections/microbiology , Clostridium Infections/prevention & control , Clostridium Infections/therapy , Diarrhea/etiology , Diarrhea/microbiology , Diarrhea/prevention & control , Diarrhea/therapy , Feces/chemistry , Feces/microbiology , Gastrointestinal Microbiome , Probiotics/administration & dosage , Probiotics/therapeutic use , Recurrence , Reinfection/prevention & control , Symbiosis , Treatment Outcome , Double-Blind Method , Bacterial Toxins/analysis , Young Adult , Aged , Aged, 80 and overABSTRACT
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.
Subject(s)
Clostridioides difficile , Clostridium Infections , Microbiota , Adult , Female , Humans , Male , Middle Aged , Anti-Bacterial Agents/adverse effects , Canada , Clostridium Infections/drug therapy , Clostridium Infections/epidemiologyABSTRACT
BACKGROUND: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes. METHODS: A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates. RESULTS: Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I2 =39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I2 =73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I2 =9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I2 =56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I2 =59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I2 =63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I2 =43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I2 =23%). CONCLUSIONS: FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.
Subject(s)
Clostridioides difficile , Clostridium Infections , Inflammatory Bowel Diseases , Adult , Humans , Child , Fecal Microbiota Transplantation/adverse effects , Treatment Outcome , Inflammatory Bowel Diseases/therapy , Clostridium Infections/therapy , RecurrenceABSTRACT
Crohn's disease is a chronic gastrointestinal inflammatory disorder, characterized by episodes of relapsing and remitting flares. As the disease mechanism becomes better elucidated, there is a significant increase in the number of available biologic therapies. This article summarizes and synthesizes current Food and Drug Administration-approved biological therapy for Crohn's disease and examines the positioning of medical therapy as emerging biologics break onto the market.
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Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.
Subject(s)
Biological Products , Colitis, Lymphocytic , Colitis, Microscopic , Inflammatory Bowel Diseases , Aged , Budesonide/therapeutic use , Cohort Studies , Colitis, Lymphocytic/complications , Colitis, Lymphocytic/diagnosis , Colitis, Lymphocytic/epidemiology , Colitis, Microscopic/diagnosis , Colitis, Microscopic/epidemiology , Colitis, Microscopic/pathology , Female , HumansABSTRACT
BACKGROUND: Restorative proctocolectomy with IPAA is the procedure of choice when colectomy is needed for medically refractory ulcerative colitis. Pouchitis is one of the most common complications among patients who have undergone IPAA and represents a spectrum of disease varying in both phenotype and clinical course. OBJECTIVE: This study aimed to assist clinicians and surgeons in the treatment of both acute and chronic pouchitis, including newer therapies and future directions. DIAGNOSIS AND MANAGEMENT: Diagnosis is made by endoscopy of the pouch with biopsy because other conditions may produce similar symptoms such as increased stool frequency, abdominal cramps, and urgency. Pouchitis is classified by duration (acute versus chronic), disease pattern (infrequent, relapsing, and continuous), and response to antibiotics (responsive, dependent, and refractory). The Pouchitis Disease Activity Index may be used to measure disease activity. The management of pouchitis is guided by the disease phenotype. Acute episodes are treated with an initial 2-week course of antibiotics (typically ciprofloxacin or metronidazole), although patients with relapsing or chronic pouchitis may require long-term antibiotic treatment or the cycling of different antibiotics. Certain probiotics may also be used for maintenance therapy in those with chronic symptoms. For patients with chronic antibiotic refractory pouchitis, oral budesonide, immunosuppressive agents (azathioprine), or biologic therapy (infliximab, adalimumab, vedolizumab, and ustekinumab) may be required for both induction and maintenance with close monitoring for potential side effects. In rare cases, diverting ileostomy or pouch excision may be required. CONCLUSION: Pouchitis represents a spectrum of disease phenotypes, ranging from acute antibiotic responsive pouchitis to chronic antibiotic refractory pouchitis. The management of pouchitis is primarily directed by the disease phenotype.