SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection.

BACKGROUND: Current therapies for recurrent Clostridioides difficile infection do not address the disrupted microbiome, which supports C. difficile spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent C. difficile infection. METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had three or more episodes of C. difficile infection (inclusive of the qualifying acute episode) received SER-109 or placebo (four capsules daily for 3 days) after standard-of-care antibiotic treatment. The primary efficacy objective was to show superiority of SER-109 as compared with placebo in reducing the risk of C. difficile infection recurrence up to 8 weeks after treatment. Diagnosis by toxin testing was performed at trial entry, and randomization was stratified according to age and antibiotic agent received. Analyses of safety, microbiome engraftment, and metabolites were also performed. RESULTS: Among the 281 patients screened, 182 were enrolled. The percentage of patients with recurrence of C. difficile infection was 12% in the SER-109 group and 40% in the placebo group (relative risk, 0.32; 95% confidence interval [CI], 0.18 to 0.58; P<0.001 for a relative risk of <1.0; P<0.001 for a relative risk of <0.833). SER-109 led to less frequent recurrence than placebo in analyses stratified according to age stratum (relative risk, 0.24 [95% CI, 0.07 to 0.78] for patients <65 years of age and 0.36 [95% CI, 0.18 to 0.72] for those ≥65 years) and antibiotic received (relative risk, 0.41 [95% CI, 0.22 to 0.79] with vancomycin and 0.09 [95% CI, 0.01 to 0.63] with fidaxomicin). Most adverse events were mild to moderate and were gastrointestinal in nature, with similar numbers in the two groups. SER-109 dose species were detected as early as week 1 and were associated with bile-acid profiles that are known to inhibit C. difficile spore germination. CONCLUSIONS: In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was similar to that of placebo. (Funded by Seres Therapeutics; ECOSPOR III ClinicalTrials.gov number, NCT03183128.).

Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (<30, 30-50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence. METHODS: We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status. RESULTS: A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years). CONCLUSIONS: Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered.

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients.

INTRODUCTION: The efficacy and safety profile of ustekinumab (UST) in Crohn's disease (CD) is favorable; however, data in elderly patients are lacking. We aimed to assess the safety and efficacy of UST in elderly CD. METHODS: We performed a retrospective cohort study of CD patients classified as elderly (age ≥ 65 years at UST initiation) or nonelderly (<65 years) treated at a large, tertiary referral center. Outcomes assessed were clinical (measured by physician global assessment [PGA]) and steroid-free response, remission, adverse events, and postsurgical complications were compared by age category. Multivariable regression modeling and survival analysis was also performed. RESULTS: In total, 117 patients (elderly n = 39, nonelderly n = 78) were included in the study. Elderly patients had predominantly moderate disease (87.2%), while nonelderly had a higher proportion of severe disease activity (44.9%) (p = 0.001), though no differences in baseline endoscopic activity, prior biologic use, or steroid or immunomodulator use at baseline existed (p > 0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p = 0.01). On regression modeling, age was not associated with clinical outcomes (p > 0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p = 0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p = 0.77), infection (5.2% vs. 7.7%, p = 0.7), or postsurgical complications (p = 0.99) by age category. CONCLUSION: UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population.

Dual Targeted Therapy for the Management of Inflammatory Bowel Disease.

The burden of inflammatory bowel disease (IBD) is increasing globally and imposes a high morbidity in patients with IBD. Advances have been made in medical management of IBD with the advent of novel therapies such as the biologics and small molecule drugs (SMDs). However, response to these medications is limited; with only 40% of patients achieving clinical remission at 1 year with a biologic. Hence, medical management of IBD is a rapidly evolving paradigm in which not only are new medications being developed but understanding how, when and in whom to use them is evolving. Dual targeted therapy (DTT), which is the combination of biologics and/or SMDs is an attractive concept as it is theoretically a potent and multidimensional anti-inflammatory treatment strategy. In this review, we present the published literature on the use of DTT and highlight its utility in clinical practice. The majority of studies on DTT are case reports and case series on the combination of dual biologic therapy. From the limited evidence available in patients with IBD, dual biologic therapy may be a safe option for patients with refractory IBD who have failed multiple biologic therapies and to manage extraintestinal manifestation of IBD. There are a handful of reports of combination therapy with a biologic and a SMD in patients with IBD. Further studies and randomized control trials are required to comprehensivretain hereely evaluate the safety and efficacy of DTT in IBD.

Antiviral Treatment for Colonic Cytomegalovirus Infection in Ulcerative Colitis Patients Significantly Improved Their Surgery Free Survival.

BACKGROUND: The frequency of cytomegalovirus (CMV) colitis in steroid-refractory inflammatory bowel disease has been reported to range from 15.8% to 34.0%. Infected patients are more likely to become hospitalized, have longer lengths of stay, and higher mortality rates. Current data are limited to small scale studies and showed conflicting result regarding the role of antiviral therapy. AIMS: (1) To investigate the role of antiviral treatment in ulcerative colitis (UC) patients with CMV infection. (2) To investigate the role of viremia in the outcomes of these patients. MATERIALS AND METHODS: The Cleveland Clinic pathology database identified 1478 patients who had colon biopsy and were tested for CMV during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected. Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14 demographic data and 4 clinical outcomes (surgery free survival, hospitalization, rehospitalization, and mortality) were compared between treated and nontreated patients. The same outcomes were also compared in patients who received treatment based on their viremia status. RESULTS: All demographic variables are similar between those treated and nontreated groups. Antiviral therapy significantly improved the surgery free survival within 30 days, and lasted 70 months (P<0.01). In contrast, hospitalization, rehospitalization, and mortality were comparable (P>0.05). No significant difference was observed in any of the clinical outcomes based on viremia status. CONCLUSIONS: Our small scale study demonstrates that antiviral treatment for colonic CMV infection significantly improves the surgery free survival short-term and long-term in patients with UC.

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

[This corrects the article DOI: 10.1100/2012/807438.].

Impact of Low Immunoglobulin G Levels on Disease Outcomes in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory bowel diseases (IBDs) are considered immune-mediated disorders with dysregulated innate and adaptive immunities. Secondary immunogloblin deficiency can occur in IBD and its impact on the disease course of IBD is not clear. AIMS: We sought to determine associations between low IgG/G1 levels and poor clinical outcomes in IBD patients. METHODS: This historic cohort study was performed on IBD patients with obtained IgG/IgG1 levels. The primary outcome was defined as any IBD-related bowel resection surgery and/or hospitalization. Subgroup analyses assessed particular surgical outcomes in Crohn's disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC), and ileal pouch-anal anastomosis (IPAA). The secondary outcomes included IBD drug escalations and C. difficile or cytomegalovirus infections. RESULTS: A total of 136 IBD patients had IgG/G1 levels checked and adequate follow-up, 58 (42.6 %) with normal IgG/G1 levels and 78 (57.4 %) having low levels. A total of 49 patients (62.8 %) with low immunoglobulin levels had IBD-related surgeries or hospitalizations, compared to 33 patients (56.9 %) with normal levels [odds ratio (OR) 1.28, 95 % confidence interval (CI) 0.64-2.56; p = 0.49]. Low IgG/G1 levels were associated with IBD-related surgery in CD in univariate analysis [hazard ratio (HR) 4.42, 95 % CI 1.02-19.23; p = 0.048] and in Kaplan-Meier survival curve analysis (p = 0.03), with a trend toward significance on multivariate analysis (HR 3.07, 95 % CI 0.67-14.31; p = 0.15). IBD patients with low IgG/G1 levels required more small bowel resections (12.8 vs. 1.7 %, p = 0.024) and 5-aminosalicylate initiations (28.2 vs. 13.8 %, p = 0.045). CONCLUSIONS: Our study demonstrated a possible association between low IgG/G1 levels and poor outcomes in CD including surgery. Future implications include using immunoglobulin levels in IBD patients as a prognostic indicator or boosting humoral immunity as a treatment in this subset.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

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.

Hospital readmissions in patients with inflammatory bowel disease.

OBJECTIVES: We aimed to identify the frequency and costs of, and the disease predictors and inpatient process issues that may predispose to, 30-day readmission for an inflammatory bowel disease (IBD) patient. METHODS: IBD patients admitted to an inpatient gastroenterology service were followed for a time-to-readmission analysis assessing factors associated with readmission within 30 days. RESULTS: Index admissions were more costly among those readmitted than among those not readmitted. Patients admitted with evidence of increased inflammation, infection, or obstruction or for dehydration or pain control had a higher risk of readmission. Patients treated with opioid analgesia during index admission were no less likely to be readmitted, and there was a 2.2-fold increase in readmissions when patients were discharged with no opioid analgesia. Scheduling variability and outpatient follow-up compliance were associated with readmission. CONCLUSIONS: Predicting readmission is complex. A predictive model developed to be used at discharge yielded an area under the curve of 0.757.

Similar outcomes of IBD inpatients with Clostridium difficile infection detected by ELISA or PCR assay.

BACKGROUND: Clostridium difficile infection (CDI) is known as a risk factor for exacerbation of inflammatory bowel disease (IBD). CDI has been most commonly tested with enzyme-linked immunosorbent assay for toxins, but with a suboptimal sensitivity. Compared with conventional ELISA, the polymerase chain reaction-based assay (PCR) is a highly sensitive detection technique for C. difficile. However, its pure detection of only the DNA of toxin B may lead to over-treatment. AIMS: The purpose of this study was to compare the frequency and clinical outcomes of IBD inpatients with CDI between the PCR and ELISA assays and to assess the factors associated with CDI. METHODS: The retrospective study was performed with the IBD inpatients at Cleveland Clinic from 2009 to 2011, who were tested by either ELISA or PCR or both. Outcomes under comparison included intensive care unit transfer, length of hospital stay, requirement for gastrointestinal surgeries and all cause re-hospitalization. Multivariable analysis was performed to assess the associated factors for the combined cohorts. RESULTS: A total of 255 patients were included, among them 222 had ELISA test, and 103 had PCR test. Thirteen (5.9 %) patients were ELISA positive, versus 14 (13.5 %) patients who were PCR positive (P = 0.02). With comparable demographic and clinical background, clinical outcomes of the ELISA and PCR positive groups showed no significant difference. Instead, the overall percentage of C. difficile positive patients had a much higher rehospitalization rate than C. difficile negative patients (P < 0.01). Multivariable analysis identified comorbidities (P = 0.03), extra-intestinal manifestations (P = 0.03) and PPI use (P < 0.01) as the associated factors for CDI. CONCLUSION: There was a greater percentage of patients tested positive by PCR compared to ELISA. The outcomes of CDI diagnosed by PCR or ELISA, however, appeared comparable. The presence of comorbidities, extra-intestinal manifestations, and the use of PPI were found to be associated with CDI.

Real-world effectiveness and safety of ustekinumab and vedolizumab in elderly patients with Crohn's disease.

Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings.

Predictors of Hospital-related Outcomes of COVID-19 Infection in Patients With Inflammatory Bowel Disease in the Early Pandemic Phase: A Nationwide Inpatient Database Survey.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at higher risk for severe COVID-19 infection. However, most studies are single-center, and nationwide data in the United States are lacking. This study aimed to investigate hospital-related outcomes and predictors of these outcomes in patients with IBD and COVID-19 infection. METHODS: The National Inpatient Sample and National Readmission database were queried for all the patient hospitalizations with IBD with concurrent COVID-19 in the study group and non-COVID-19 related hospitalizations in the control group. For patients under 18 years, elective and trauma-related hospitalizations were excluded. Primary outcomes included mortality, septic shock, mechanical ventilation, and intensive care utilization. Secondary outcomes included length of stay and total hospitalization costs. RESULTS: From this query, 8865 adult patients with IBD and COVID-19 were identified. These patients were relatively older (62.8 vs 57.7 years, P < .01), and the majority were females (52.1% with COVID-19 vs 55.2% without COVID-19). Patients with IBD and COVID-19 had higher mortality (12.24% vs 2.55%; P < .01), increased incidence of septic shock (7.9% vs 4.4%; P < .01), mechanical ventilation (11.5% vs 3.7%; P < .01), and intensive care utilization (12% vs 4.6%; P < .01). These patients also had higher mean length of stay (8.28 days vs 5.47 days; P < .01) and total hospitalization costs ($21 390 vs $16 468; P < .01) than those without COVID-19 infection. CONCLUSIONS: Patients with IBD and COVID-19 have worse outcomes, with a higher incidence of severe COVID-19 disease, leading to higher mortality rates, longer lengths of stay, and increased total hospitalization costs. Encouraging preventive health measures and treating promptly with advanced COVID-19 therapies may improve outcomes and decrease the healthcare burden.

This study used nationwide data to examine hospital-related outcomes in patients with inflammatory bowel disease (IBD) and COVID-19 disease. Patients with IBD and COVID-19 had higher mortality, septic shock, mechanical ventilation, and intensive care utilization rates. They also experienced higher costs and longer hospital stays, highlighting the need for preventive measures and timely treatment to improve outcomes and reduce healthcare burden.

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.

Progressive primary sclerosing cholangitis requiring liver transplantation is associated with reduced need for colectomy in patients with ulcerative colitis.

BACKGROUND & AIMS: We investigated the association between the severity of primary sclerosing cholangitis (PSC) and clinical outcomes of patients with ulcerative colitis (UC) on the basis of need for colectomy. METHODS: We analyzed data from 167 patients with PSC and UC who were followed from 1985 to 2011. Patients with PSC and UC were divided into groups that received orthotopic liver transplantation (OLT) (n = 86) or did not (non-OLT, n = 81). Clinical and demographic variables were obtained, and patients were followed until they received OLT or the date of their last clinical visit. RESULTS: The OLT group had significantly more subjects with less severe symptoms of UC (59, 68.6%) than the non-OLT group (12, 14.8%; P < .001). The subjects in the OLT group had a median of 0 UC flares compared with 3 in the non-OLT group (P < .001); fewer subjects in the OLT group required use of azathioprine or mercaptopurine (1, 1.2%), compared with the non-OLT group (14, 17.3%; P = .006). More subjects in the non-OLT group required colectomies (61, 75.3%) than in the OLT group (23, 26.7%; P < .001). On the basis of Cox regression analysis, OLT for PSC independently reduces the need for colectomy (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.25-0.75; P = .003), as does a high Mayo risk score at diagnosis (HR, 0.52; 95% CI, 0.37-0.72; P < .001). Development of colon neoplasia increased the risk for colectomy (HR, 2.47; 95% CI, 1.63-3.75; P < .001). CONCLUSIONS: Severe progressive PSC that requires liver transplantation appears to reduce the disease activity of UC and the need for colectomy.

Duration and severity of primary sclerosing cholangitis is not associated with risk of neoplastic changes in the colon in patients with ulcerative colitis.

BACKGROUND: Annual surveillance colonoscopy to detect colon cancer is recommended for patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). Limited data currently support these recommendations. OBJECTIVE: To study whether a relationship exists between the severity and duration of PSC and the risk of colon cancer and dysplasia (colon neoplasia). DESIGN: Retrospective, longitudinal study. SETTING: Tertiary-care referral center. PATIENTS: Information pertaining to duration of PSC, UC, requirement for orthotopic liver transplantation, and time to diagnosis of colon neoplasia was obtained for patients with PSC and UC. Patients were evaluated and followed-up from 1985 to 2011 at a single institution. MAIN OUTCOME MEASUREMENTS: Association between the severity and duration of PSC-UC and the time of occurrence of colon neoplasia. RESULTS: Of 167 patients with a combined diagnosis of PSC-UC, 55 had colonic neoplasia on colonoscopy. Colonic neoplasia occurred more frequently within 2 years of a combined diagnosis of PSC-UC (6.6/100 patient-years of follow-up) than after 8 years from PSC-UC (2.7/100 patient-years of follow-up). On proportional hazards analysis, older age at PSC diagnosis (hazard ratio 1.23 for every 5 years; 95% confidence interval, 1.03-1.34; P = .014) increased the risk of colon neoplasia. LIMITATIONS: Retrospective study. CONCLUSION: In this study, the severity of PSC was not significantly associated with the risk of colon neoplasia. Patients with PSC and UC have a high risk of colon neoplasia soon after the coexistence of the two diseases is discovered. Older age at PSC diagnosis increases this risk.

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.

Intra-abdominal septic complications after ileocolic resection increases risk for endoscopic and surgical postoperative Crohn's disease recurrence.

BACKGROUND: Postoperative recurrence [POR] of Crohn's disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated. AIMS: To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR. METHODS: This was a retrospective study of adult Crohn's disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts' score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence. RESULTS: In 535 Crohn's disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [N = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23-4.97]; p = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04-2.45]; p = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04-4.87] p = 0.03) and decreased survival-free time [aHR: 2.53 [1.31-4.87]; p = 0.006] for surgical recurrence. CONCLUSION: IASC is associated with an increased risk for endoscopic and surgical POR of Crohn's disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR.

Mild neoterminal ileal post-operative recurrence of Crohn's disease conveys higher risk for severe endoscopic disease progression than isolated anastomotic lesions.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease. METHODS: Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence. RESULTS: One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86). CONCLUSION: Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Once-daily dosing of delayed-release oral mesalamine (400-mg tablet) is as effective as twice-daily dosing for maintenance of remission of ulcerative colitis.

BACKGROUND & AIMS: The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients. METHODS: A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6-2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6. RESULTS: A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events. CONCLUSIONS: Once-daily dosing of delayed-release mesalamine at doses of 1.6-2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC.