Predictors of Response to Vedolizumab in Patients with Ulcerative Colitis: Results from the Greek VEDO-IBD Cohort.

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

Post-inflammatory Polyp Burden as a Prognostic Marker of Disease-outcome in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Post-inflammatory polyps [PIPs] are considered as indicators of previous episodes of severe inflammation and mucosal ulceration. Inflammatory bowel disease [IBD], namely Crohn's disease [CD] and ulcerative colitis [UC], exhibit a perpetuating, relapsing and remitting pattern, and PIPs are a frequent sequela of chronicity. The aim of this study was to determine whether a high PIP burden is associated with a more severe disease course in patients with IBD. METHODS: This was a multinational, multicentre, retrospective study. IBD patients previously diagnosed with PIPs were retrieved from the endoscopic database of each centre. PIP burden was evaluated and associated with demographic and clinical data as well as factors indicating a more unfavourable disease course. RESULTS: A total of 504 IBD patients with PIPs were recruited [male: 61.9%]. The mean age at IBD diagnosis was 36.9 [±16.8] years. Most patients [74.8%] were diagnosed with UC. A high PIP burden was present in 53.4% of patients. On multivariable Cox regression analysis, a high PIP burden was independently associated with treatment escalation (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.04-1.75; p = 0.024), hospitalization [HR 1.90; 95% CI 1.24-2.90; p = 0.003], need for surgery [HR 2.28; 95% CI 1.17-4.44, p = 0.02] and younger age at diagnosis [HR 0.99, 95% CI 0.98-0.99; p = 0.003]. CONCLUSION: PIP burden was associated with a more severe outcome. Future prospective studies should focus on the characterization of PIP burden as to further risk stratify this patient cohort.

Is there any role of renin-angiotensin system inhibitors in modulating inflammatory bowel disease outcome?

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been associated with improved outcomes in inflammatory bowel disease. We aimed to investigate any possible effect of antihypertensive medications on inflammatory bowel disease course. METHODS: One hundred and fifty inflammatory bowel disease patients with hypertension were compared using a 1:1 ratio with age- and gender-matched control patients with inflammatory bowel disease. The class of antihypertensive medication, traditional risk factors for atherosclerosis, inflammatory bowel disease characteristics, and history (surgery, hospitalizations, and treatment) were retrospectively analyzed. RESULTS: Of 150 (44.7% Crohn's disease) patients with hypertension, 46.7% were on angiotensin receptor blockers, 30.6% on angiotensin-converting enzyme inhibitors, 40% on ß-blockers, and 40.7% on calcium channel blockers. Univariate analysis revealed significantly higher rates of traditional risk factors for atherosclerosis among antihypertensive users. When analyzing by class of antihypertensive medication, angiotensin receptor blockers were significantly associated with milder course as indicated by less frequent immunomodulator (P = 0.039) and steroid use (P = 0.041). Rates of lifetime steroids were statistically significantly lower among angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (odds ratio = 1.191, 95% confidence interval, 1.005-1.411). After adjustment with confounding factors, only angiotensin receptor blockers were associated with milder inflammatory bowel disease course (P = 0.037) and lower rates of immunomodulator use (P = 0.038). CONCLUSIONS: Our study suggests a possible protective effect of angiotensin receptor blockers on overall inflammatory bowel disease course by targeting the renin-angiotensin system. Their effect on inflammatory bowel disease needs to be studied in larger cohorts.

Eosinophilic Esophagitis in Adults: A Concise Overview of an Evolving Disease.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that encompasses esophageal symptoms along with eosinophilic infiltration of the esophageal epithelium. EoE is an evolving disease that has been a subject of interest to many researchers since the first studies recognized this condition as a new and distinct clinicopathological entity 25 years ago. Clinical presentation in adult patients may include dysphagia, food impaction, vomiting, and reflux symptoms. The diagnosis of EoE is based on the combination of clinical history suggestive of esophageal dysfunction, endoscopic features indicative of the disease, and histology revealing eosinophilic infiltration of the esophageal epithelium that persists after a trial of proton pump inhibitor therapy along with the exclusion of other disorders that may be associated with esophageal tissue eosinophilia. The interplay between EoE and gastroesophageal reflux disease (GERD) is complex, and differentiating these two conditions continues to be difficult and challenging in clinical practice. The mainstay treatment includes dietary modification, topical steroids, and/or endoscopic dilation. The primary care physician (PCP) plays an important role in improving patient care and quality of life by ensuring early referral and participating in management and follow-up. This article provides an overview of the current knowledge base regarding the disease including epidemiology, genetics, pathogenesis, common clinical presentations, the interplay between EoE and GERD, diagnostic approaches, and therapeutic options available to the PCP.

The role of coexisting cardiovascular disease on disease severity in patients with inflammatory bowel disease.

OBJECTIVES: Chronic inflammation has been implicated in the pathogenesis of atherosclerosis and cardiovascular disease. Data linking the severity of inflammatory bowel disease to coexisting cardiovascular disease are scarce. The aim of the present study was to investigate whether inflammatory bowel disease patients with coexistent cardiovascular disease have more severe disease. METHODS: We included 103 inflammatory bowel disease patients with coexisting cardiovascular disease compared to 206 age- and sex-matched inflammatory bowel disease patients without cardiovascular disease derived from three referral inflammatory bowel disease Centers. Traditional cardiovascular disease factors and parameters of inflammatory bowel disease severity were compared between the two groups. RESULTS: Cardiovascular disease was diagnosed after the inflammatory bowel disease diagnosis in 56.6% of cases. No significant difference was found in the prevalence of surrogate markers of severity (inflammatory bowel disease-related surgeries, hospitalizations, biologics or immunosuppressants' use, and persistent CRP elevation) between inflammatory bowel disease patients with and without cardiovascular disease. There was no difference between cardiovascular disease patients diagnosed before and after inflammatory bowel disease onset. All traditional risk factors (hypertension, dyslipidemia, smoking, obesity, diabetes mellitus) were significantly more common in cardiovascular disease patients. Cardiovascular disease patients had a trend for lower rates of multiple hospitalizations (16.5% vs. 24.3%, P = 0.05) and inflammatory bowel disease-related surgeries (P = 0.09). CONCLUSION: The inflammatory burden possibly plays a less important role in the development of cardiovascular disease in inflammatory bowel disease patients but future larger prospective studies are needed.

Screening and surveillance methods for dysplasia in inflammatory bowel disease patients: Where do we stand?

Patients with long-standing ulcerative colitis (UC) and extensive Crohn's colitis (CC) are at increased risk for dysplasia and colorectal cancer (CRC). Several studies have shown that UC extending proximal to the rectum, CC involving at least 1/3 of the colon, co-existence of primary sclerosing cholangitis, undetermined or unclassified colitis, family history of CRC and young age at diagnosis appear to be independent risk factors for inflammatory bowel disease (IBD) - related CRC. Therefore, screening and surveillance for CRC in IBD patients is highly recommended by international and national guidelines, whilst colonoscopy remains the unequivocal tool in order to detect potentially resectable dysplastic lesions or CRC at an early stage. Although the importance of screening and surveillance is widely proven, there is a controversy regarding the time of the first colonoscopy and the criteria of who should undergo surveillance. In addition, there are different recommendations among scientific societies concerning which endoscopic method is more efficient to detect dysplasia early, as well as the terminology for reporting visible lesions and the management of those lesions. This article concisely presents the main endoscopic methods and techniques performed for detecting dysplasia and CRC surveillance in patients with IBD focusing on their evidence-based accuracy and efficiency, as well as their cost-effectiveness. Finally, newer methods are mentioned, highlighting their applicability in daily endoscopic practice.

Effectiveness and Safety of Vedolizumab in Anti-TNF-Naïve Patients With Inflammatory Bowel Disease-A Multicenter Retrospective European Study.

Background: Vedolizumab (VDZ) is effective for treatment of ulcerative colitis (UC) and Crohn's disease (CD). In GEMINI trials, anti-tumor necrosis factor (anti-TNF)-naïve patients had a superior response compared with anti-TNF-exposed patients. In real-world experience (RWE), the number of included anti-TNF-naïve patients was low. We aimed to evaluate the effectiveness and safety of VDZ in anti-TNF-naïve patients in an RWE setting. Methods: This retrospective multicenter European pooled cohort study included consecutive active anti-TNF-naïve IBD patients treated with VDZ. The primary end point was clinical response at week 14. Patients with follow-up beyond week 14 and those discontinuing VDZ at any time were included for maintenance outcomes analysis. Results: Since January 2015, 184 anti-TNF-naïve patients from 23 centers initiated VDZ treatment (Crohn's disease [CD], 50; ulcerative colitis [UC], 134). In CD, 42/50 (82%) patients responded by week 14 and 32 (64%) were in clinical remission; 26/50 (52%) achieved corticosteroid-free remission (CSFR). At last follow-up (44 weeks; interquartile range [IQR], 30-52 weeks), 27/35 (77.1%) patients with available data responded to treatment; 24/35 (68.6%) were in clinical remission, 21/35 (60%) were in CSFR. For UC, 116/134 (79.1%) responded to treatment by week 14, including 53 (39.5%) in clinical remission; 49/134 (36.6%) achieved CSFR. At last follow-up (42.5 weeks; IQR, 30-52 weeks), 79/103 (76.7%) patients responded to treatment, 69/103 (67.0%) were in remission, and 61/103 (59.2%) were in CSFR. Adverse effects were reported in 20 (11%) of the patients, leading to treatment discontinuation in 6 (3.3%). Conclusions: VDZ is similarly effective in ant-TNF-naïve CD and UC patients. The efficacy is higher than reported in anti-TNF-experienced patients and is comparable to that of anti-TNF biologics in this population.

Proton pump inhibitor and selective serotonin reuptake inhibitor therapy for the management of noncardiac chest pain.

INTRODUCTION: Although gastroesophageal reflux disease is the main cause of noncardiac chest pain (NCCP), proton pump inhibitors (PPIs) benefit a minority of patients. Our prospective study evaluated the effect of PPI and selective serotonin reuptake inhibitors on the different subtypes of NCCP characterized by impedance-pH monitoring. METHODS: All NCCP patients underwent impedance-pH monitoring and on the basis of the results, those with abnormal distal esophageal acid exposure received PPIs twice daily (group A), those with a positive symptom index for chest pain received citalopram 20 mg and PPI once daily (group B), and those with a negative symptom index for chest pain received citalopram 20 mg once daily (group C). Therapy was administered for 12 weeks and treatment success was defined as complete disappearance of chest pain. RESULTS: From March 2015 to March 2016, 63 patients were included (group A=9, group B=18, group C=36). After 12 weeks of therapy, complete resolution of chest pain was noted in 8/9 (88.9%) group A, 13/18 (72.2%) group B, and 24/36 (66.7%) group C patients. CONCLUSION: Combined impedance-pH monitoring identifies different subtypes of NCCP patients who can receive tailored management. Targeted therapy with PPIs and/or citalopram offers complete symptom relief in the great majority of them.

Investigation of extraesophageal gastroesophageal reflux disease.

The most common extraesophageal manifestations of gastroesophageal reflux disease (GERD) include chronic cough, asthma and laryngitis. There are two mechanisms proposed to explain extraesophageal syndromes caused by GERD. The first one is a direct way via irritation and/or microaspiration and the second one is an indirect, vagally mediated way. The investigation of extraesophageal manifestations of GERD is difficult and the empirical therapy with proton pump inhibitors usually double dose for at least three months is still the most common approach.

The role of weakly acidic reflux in proton pump inhibitor failure, has dust settled?

Patients that do not respond satisfactorily to standard proton pump inhibitor (PPI) treatment have become the most common presentation of gastro-esophageal reflux disease (GERD) in third referral gastrointestinal practices. The causes of refractory GERD include lack of compliance with treatment, residual acid reflux and weakly acidic reflux, esophageal hypersensitivity and persistent symptoms not associated with reflux. A role for weakly acidic reflux in symptom generation has been proposed since the availability of impedance-pH monitoring. The possible mechanisms by which persistent weakly acidic reflux might contribute to persistent symptoms in patients under PPI treatment may include esophageal distension by increased reflux volume, persistent impaired mucosal integrity (ie, dilation of intercellular spaces) and/or esophageal hypersensitivity to weakly acidic reflux events. To establish a definite role of weakly acidic reflux in refractory GERD, outcome studies targeting this type of reflux are still lacking. Treatment strategies to reduce the number or effect of weakly acidic reflux could involve drugs that decrease transient lower esophageal sphincter relaxations (ie, baclofen or similar), improve oesophageal mucosa resistance or visceral pain modulators. Finally, anti-reflux surgery can be considered, only if a clear symptom-weakly acidic reflux association was demonstrated.