Khadija Chaudrey

The Real-World Effectiveness and Safety of Vedolizumab for Moderate-Severe Crohn's Disease: Results From the US VICTORY Consortium.

Objectives:We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate–severe Crohn’s disease (CD).Methods:Retrospective cohort study of seven medical centers, from May 2014 to December 2015. Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included. Using the multivariable Cox proportional hazard analyses, we identified independent predictors of clinical remission or mucosal healing with VDZ. Rates of serious infection (requiring antibiotics, resulting in discontinuation of VDZ, hospitalization or death) and serious adverse events (discontinuation of VDZ, hospitalization or death) were described quantitatively.Results:We included 212 patients with moderate–severe CD (median age 34 years; 40% male; 90% tumor necrosis factor (TNF)-antagonist exposed) with a median follow-up (IQR) of 39 weeks (25–53). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission+mucosal healing) were 35%, 63%, and 26%, respectively. Individuals with prior TNF-antagonist exposure (hazard ratio (HR) 0.40; 95% confidence interval (CI): 0.20–0.81), smoking history (HR 0.47; 95% CI: 0.25–0.89), active perianal disease (HR 0.49; 95% CI: 0.27–0.88), and severe disease activity (HR 0.54; 95% CI: 0.31–0.95) were less likely to achieve clinical remission. Those with prior TNF-antagonist exposure (HR 0.29; 95% CI: 0.12–0.73), and severe disease activity (HR 0.54; 95% CI: 0.31–0.95) were less likely to achieve mucosal healing. During 160 patient years of follow-up (PYF) and 1,433 VDZ infusions, 5 patients developed infusion reactions (3.5 per 1,000 infusions), 21 developed serious infections (13 per 100 PYF), and 17 developed serious adverse events (10 per 100 PYF). A minority of adverse events required discontinuation of therapy (6 per 100 PYF).Conclusions:VDZ is a safe and effective treatment option for moderate–severe CD in routine practice. Clinical remission and deep remission (clinical remission and mucosal healing) can be achieved in 1/3 of individuals, and a minority of individuals require discontinuation of therapy due to adverse events.

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.

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

Background We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods Retrospective 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. Results Cumulative 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. Conclusions LOR 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.

State of the Art and Future Predictions: “By the Way… I’m Pregnant”

There are multiple concerns women have about becoming or being pregnant when they have irritable bowel syndrome (IBD). Fertility can be impaired in those who have had previous pelvic surgery, and impaired sexuality been reported as well. The majority of pregnancies result in healthy children, as there is no apparent increased risk for birth defects, childhood infections, or cancers. However, women with active IBD during pregnancy can have babies that are small for gestational age, low birth weight, and premature. The data for the safety of medications during pregnancy is favorable, and women are encouraged to stay on therapy to control the disease while pregnant.

State of the Art and Future Predictions: Isn’t There a Test for That? Diagnosing IBD

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that includes Crohn’s disease (CD) and ulcerative colitis (UC). A diagnostic workup is often triggered by presenting symptoms of the patient. A combination of laboratory tests, imaging modalities, endoscopy, and histopathology is utilized to establish the diagnosis. These diagnostic tests not only assist in establishing the diagnosis of IBD but also help distinguish CD from UC, assess disease activity, and exclude other competing diseases in the differential diagnoses. This chapter reviews the diagnostic tests available for establishing the diagnosis of IBD.

Sa1237 Epidemiological Features and Risk Factors Affecting Outcomes of Clostridium difficile Infection Among Inpatients At an Urban Hospital

G A A b st ra ct s in an inpatient cohort from Olmsted County, MN. Information on maximum change in serum creatinine (highest value compared to baseline over the past year) and WBC within 7 days of CDI diagnosis was obtained for three groups: pediatrics ( ,18 yrs old), adults (18-65), and the elderly (.65). Sensitivity (Se) and specificity (Sp) of various levels of WBC and creatinine ratio were estimated for predicting severe-complicated CDI, defined as need for ICU admission, colectomy, or death. Analysis of creatinine ratio in the pediatric population was not done due to a high proportion of missing baseline creatinine values. The cohort included 1446 patients (48.6% female, median age 62.5 yrs [range, 0.1-103.7]); 487 (33.7%) had severe-complicated CDI. A WBC .15 x10^9/L (the cut-off recommended in expert guidelines) had a similar Se and Sp for predicting severe-complicated CDI in pediatrics (Se= 54.5, Sp=78.8), adults (Se=53.7, Sp=73.2), and the elderly (Se=56.3, Sp=63.5). A serum creatinine ratio of 1.5 had a similar ability to predict severe-complicated CDI in adults (Se= 59.2, Sp=59.5) and the elderly (Se=61.9, Sp=54.1). Lowering the thresholds of WBC and creatinine ratio increased the Se but decreased the Sp for predicting severe-complicated CDI in all age groups. For example, lowering the WBC threshold to 12.5 or decreasing the creatinine threshold to 1.4 increases the Se by 10-18% with a similar decrease in Sp (Table 1). No optimal WBC or creatinine rise cut-offs to predict severe-complicated CDI were defined in this investigation. The current cut-off values according to expert guidelines performed similarly across age groups, but had relatively low sensitivities and specificities. For all age groups and for both WBC and creatinine rise, decreasing the cut-off value increased the sensitivity while decreasing the specificity; these variables should be considered as continuous predictors of complicated CDI, with higher values indicating higher risk. Values below the threshold values defined in current guidelines do not reliably exclude a significant risk of complicated CDI. Given the poor outcomes in patients with severecomplicated CDI and the recommendation that treatment be stratified by severity, a more sensitive predictor (lower WBC or creatinine cut-offs) may be more appropriate. Table 1. Sensitivities and specificities of peripheral leukocyte count and serum creatinine rise in predicting severe-complicated Clostridium difficile infection.