Matthew Bohm

Diagnosis and Management of Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth (SIBO) can result from failure of the gastric acid barrier, failure of small intestinal motility, anatomic alterations, or impairment of systemic and local immunity. The current accepted criteria for the diagnosis of SIBO is the presence of coliform bacteria isolated from the proximal jejunum with >10(5) colony-forming units/mL. A major concern with luminal aspiration is that it is only one random sampling of the small intestine and may not always be representative of the underlying microbiota. A new approach to examine the underlying microbiota uses rapid molecular sequencing, but its clinical utilization is still under active investigation. Clinical manifestations of SIBO are variable and include bloating, flatulence, abdominal distention, abdominal pain, and diarrhea. Severe cases may present with nutrition deficiencies due to malabsorption of micro- and macronutrients. The current management strategies for SIBO center on identifying and correcting underlying causes, addressing nutrition deficiencies, and judicious utilization of antibiotics to treat symptomatic SIBO.

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients.

Vedolizumab for Ulcerative Colitis: Treatment Outcomes from the VICTORY Consortium

OBJECTIVES: We aimed to quantify the safety and effectiveness of vedolizumab (VDZ) when used for UC, and to identify predictors of response to treatment. METHODS: Retrospective review (May 2014‐December 2016) of VICTORY Consortium data. Adults with follow‐up after starting VDZ for clinically active UC were included. Primary effectiveness outcomes were cumulative rates of clinical remission (resolution of all UC‐related symptoms) and endoscopic remission (Mayo endoscopic sub‐score 0). Key secondary effectiveness outcomes included cumulative rates of corticosteroid‐free remission and deep remission (clinical remission and endoscopic remission). Cox proportional hazard analyses were used to identify independent predictors of treatment effectiveness. Non‐response imputation (NRI) sensitivity analyses were performed for effectiveness outcomes. Key safety outcomes were rates of serious infection, serious adverse events, and colectomy. RESULTS: We included 321 UC patients (71% prior TNF&agr; antagonist exposure, median follow‐up 10 months). The 12‐month cumulative rates of clinical remission and endoscopic remission were 51% and 41%, respectively. Corresponding rates for corticosteroid‐free remission and deep remission were 37% and 30%, respectively. Using NRI, 12‐month rates were 20% (n = 64/321) for clinical remission, 17% (n=35/203) for endoscopic remission, 15% (n=30/195) for corticosteroid‐free remission, and 14% (n = 28/203) for deep remission. A majority of the patients without adequate follow‐up at 12 months who were deemed non‐responders using NRI had already achieved clinical remission (n = 70) or a significant clinical response (n=36) prior to 12 months. VDZ discontinuation prior to 12 months was observed in 91 patients, for lack of response (n =56), need for surgery (n=29), or adverse event (n=6). On multivariable analyses, prior exposure to a TNF&agr; antagonist was associated with a reduced probability of achieving clinical remission (HR 0.53, 95% CI 0.38–0.75) and endoscopic remission (HR 0.51, 95% CI 0.29–0.88). Serious adverse events and serious infections were reported in 6% and 4% of patients, respectively. Overall cumulative rates of colectomy over 12 months were 13%, with lower rates observed in patients naive to TNF&agr; antagonist therapy (2%) than those who had been exposed to TNF&agr; antagonists (19%). CONCLUSION: In this large real‐world cohort we observed that VDZ was well tolerated and effective in achieving key clinical outcomes.

Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease

BACKGROUND & AIMSnAs more treatment options for inflammatory bowel diseases become available, it is important to identify patients most likely to respond to different therapies. We created and validated a scoring system to identify patients with Crohns disease (CD) who respond to vedolizumab.nnnMETHODSnWe collected data from the GEMINI 2 phase 3 trial of patients with active CD treated with vedolizumab for 26 weeks (nxa0= 814) and performed logistic regression analysis to identify factors associated with clinical, steroid-free, and durable remission (derivation set). We used these data to develop a clinical decision support tool, which we validated using data from 366 participants in a separate clinical practice observational cohort of patients with active CD treated with vedolizumab for 26 weeks (the VICTORY cohort). We evaluated the ability of this tool to identify patients in clinical remission or corticosteroid-free remission, or those with mucosal healing (MH), clinical remission with MH, or corticosteroid-free remission with MH after vedolizumab therapy using receiver operating characteristic area under the curve (AUC) analyses. The primary outcome was to develop and validate a list of factors associated with achieving remission by vedolizumab in patients with active CD.nnnRESULTSnIn the derivation analysis, we identified absence of previous treatment with a tumor necrosis factor antagonist (+3 points), absence of prior bowel surgery (+2 points), absence of prior fistulizing disease (+2 points), baseline level of albumin (+0.4 points per g/L), and baseline concentration of C-reactive protein (reduction of 0.5 points for values between 3.0 and 10.0 mg/L and 3.0 points for values >10.0 mg/L) as factors associated with remission. In the validation set, our model identified patients in clinical remission with an AUC of 0.67, patients in corticosteroid-free remission with an AUC of 0.66, patients with MH with an AUC of 0.72, patients in clinical remission with MH with an AUC of 0.73, and patients in corticosteroid-free clinical remission with MH with an AUC of 0.75. A cutoff value of 13 points identified patients in clinical remission after vedolizumab therapy with 92% sensitivity, patients in corticosteroid-free remission with 94% sensitivity, patients with MH with 98% sensitivity, patients with clinical remission and MH with 100% sensitivity, and patients with corticosteroid-free clinical remission with MH with 100% sensitivity.nnnCONCLUSIONSnWe developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.

Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease

BackgroundnWe quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR.nnnMethodsnRetrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified.nnnResultsnCumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohns disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohns disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients.nnnConclusionsnLOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases

BACKGROUND & AIMSnThere are few real-world data on the safety of vedolizumab for treatment of Crohns disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice.nnnMETHODSnWe performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs.nnnRESULTSnOur analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (nxa0= 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (nxa0= 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (nxa0= 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections.nnnCONCLUSIONnIn a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.