Farhad Peerani

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.

Management and Prevention of Herpes Zoster in the Immunocompromised Inflammatory Bowel Disease Patient: A Clinical Quandary.

Abstract:Crohns disease (CD) and ulcerative colitis (UC), the 2 main clinical phenotypes of inflammatory bowel disease (IBD), are diseases that result from a dysregulated immune response to gut microbiota in genetically susceptible hosts. This aberrant immune response may intrinsically predispose IBD patients to infectious complications. Moreover, immunosuppressive medications used to treat IBD including corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, anti-tumor necrosis factor (anti-TNF) agents and other biologics, further increase patients susceptibility to opportunistic infections. Herpes zoster (HZ), also known as shingles, is an opportunistic viral reactivation often observed in IBD patients with several case reports demonstrating complicated or disseminated disease in those on immunosuppression. While HZ vaccination is recommended in all immunocompetent adults aged ≥60 years, as a live virus vaccine, it is currently contraindicated in IBD patients on anti-TNF therapy and in other significantly immunocompromised patient groups. While caution is still warranted in these circumstances, recent clinical data has emerged which has prompted us to review and examine the universal approach to HZ vaccination in the immunosuppressed IBD population. In the following narrative review, we will discuss and provide an overview of the clinical manifestations, incidence, management and prevention of HZ in the IBD patient.

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.

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.

Letter: the safety of herpes zoster vaccination for patients with inflammatory bowel disease being treated with anti-TNF medications

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Patients with Active Luminal Crohn's Disease Have Evidence of Significant Functional and Clinical Pulmonary Involvement.

Background:Pulmonary involvement is a recognized extraintestinal complication of inflammatory bowel disease and is associated with airway inflammation. Changes in pulmonary function were previously described as being subclinical. The purpose of this study was to compare pulmonary findings in a large case series of patients with active and quiescent Crohns disease (CD). Methods:CD patients, prospectively enrolled between May 2011 and May 2012, completed a demographic questionnaire and Harvey–Bradshaw Index to define disease activity. Each patient also completed blood work, a chest x-ray, pulmonary function testing, respiratory symptom and dyspnea scoring, and a 6-minute walk test. Results are reported as mean ± SE or descriptively as a percent and were analyzed using t tests and chi-square or Fishers exact tests, respectively. Multivariable linear regression models were built for continuous outcomes and logistic regression models for categorical outcomes. Results:Ninety-five patients (54 remission, 41 active disease), 58.9% males, with a mean age of 41 ± 1 years were enrolled. Patients with active disease compared with those in remission had lower absolute ratios of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (0.74 ± 0.01 versus 0.77 ± 0.01, P = 0.023), higher degrees of peripheral airway obstruction (34.1% versus 16.7%, P = 0.049), more frequent respiratory symptoms (29.3% versus 9.3%, P = 0.012) and higher Medical Research Council (MRC) dyspnea scales (MRC 2 or 3, 58.5% versus 22.2%, P = 0.001), respectively. Conclusions:CD patients with active disease display clinical pulmonary dysfunction compared with those in remission.

Optimal Management of Fistulizing Crohn’s Disease

Fistulizing Crohn’s disease (CD) is a debilitating phenotype, having a substantial effect on quality of life. Optimal outcomes for the management of fistulizing CD occur when patients are treated in a multidisciplinary setting with medical, radiological, and surgical expertise. Ideally patients should be evaluated by any two of the following: examination under anesthesia (EUA), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS). Furthermore, sigmoidoscopy is critical to assess for anal stenosis and active proctitis, which can alter surgical management. Most of the literature focuses on the management of perianal fistulizing CD with the strongest evidence available for anti-tumor necrosis factor α (anti-TNF α) therapy used in conjunction with antibiotics for induction and potentially thiopurines for maintenance. With an approximately 50 % fistula response rate in the biologic era, there is still an unmet medical need for this subset of CD patients.