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.

Evaluation of parameters influencing the quality of colon preparation with a split-dose regimen of sulfate salts.

Background: Bowel cleansing is an important factor for the quality of colonoscopy. We aimed to evaluate the efficacy of split-dose oral sulfate salts on bowel preparation and to determine parameters influencing the quality of bowel cleaning. Method: Consecutive adults who completed their preparation for colonoscopy with a regimen of sulfate salts were enrolled. Results: Of the 446 patients, 11 were excluded from the analysis. Among the 435 patients, 257 (59.1%) were female, mean age was 62.0±11.6 years and median body mass index (BMI) 26.1 kg/m2 (interquartile range [IQR] 23.8-29.4). Indications for colonoscopy were screening 155 (35.6%), surveillance 102 (23.5%), or other 178 (40.9%). The median time between the end of second dose of the preparation regimen and colonoscopy initiation was 5:15 h (IQR 4:30-6:00, min: 2:20, max: 12:20). Minor adverse events were reported in 62 (14.3%) patients. BBPS=9 was observed in 279 (64.14%) patients. Segmental BBPS=3 was achieved in 387 (88.97%), 346 (79.54%) and 289 (66.44%) patients (P<0.001) in the descending, transverse and ascending colon, respectively. Multivariate analysis revealed that BMI (odds ratio [OR] 1.05, 95% confidence interval [CI] 1-1.1) and time between the end of the second laxative dose and colonoscopy initiation (OR 1.25, 95%CI 1.08-1.45) were associated with poorer bowel preparation. Conclusions: A split dose of oral sulfate salts is an efficacious and well tolerated regimen. Obesity and a longer time interval between the end of the second dose and colonoscopy initiation negatively influence bowel cleanliness.

Prevalence and predictors of arthralgia after initiation of vedolizumab in patients with inflammatory bowel disease: a retrospective cohort study.

OBJECTIVES: Vedolizumab is a mAb used for the treatment of moderate to severe ulcerative colitis and Crohn's disease. There is evidence that administration of vedolizumab has been associated with either new onset or reactivation of extra-intestinal manifestations, among which arthralgia is the most prominent. We aimed to study the incidence, characteristics and predictors for the occurrence of arthralgias in patients with inflammatory bowel disease (IBD) who receive vedolizumab. METHODS: A retrospective cohort study was implemented in patients with IBD. The occurrence of new-onset and recurrent arthralgias were recorded. Multivariate Cox proportional-hazards models were used to identify factors associated with the endpoints of interest. RESULTS: A total of 115 vedolizumab-treated IBD patients (male = 50.4%; ulcerative colitis = 70.4%; median follow-up = 12.7 months) participated. New-onset arthralgia occurred in 20.9%, and recurrent in 46.7% (45 patients at risk). Among patients with ulcerative colitis, multivariate Cox's proportional-hazards models showed, that new onset arthralgia was significantly associated with extensive colitis (hazard ratio = 2.91; 95% confidence interval, 1.04-8.12). Of 15 patients with concomitant treatment of azathioprine, no one manifested new-onset arthralgia (X2P = 0.03; Fisher's exact test P = 0.038). No predictors were identified for recurrent arthralgia. CONCLUSION: Arthralgias is a common manifestation of vedolizumab treatment. Patients with extensive ulcerative colitis demonstrate a higher risk for new-onset arthralgia, whereas, concomitant treatment with azathioprine appears to be protective. These associations may be mediated by re-directed lymphocyte trafficking and may support concomitant immunomodulator administration in specific patient subpopulations who commence treatment with vedolizumab.

Retroflexion, a costless endoscopic maneuver, increases adenoma detection rate in the ascending colon.

BACKGROUND: Missed polyps during colonoscopy are considered an important factor for interval cancer appearance, especially in the ascending colon (AC). We evaluated the contribution of retroflexion to polyp and adenoma detection in the AC. METHODS: This prospective observational study included consecutive patients who underwent a complete colonoscopy between 06/2017 and 06/2018. The AC was examined in 2 phases: the first included 2 forward views from the hepatic flexure to the cecum; the second involved a retroflexion in the cecum, inspection up to the hepatic flexure and reinsertion to the cecum. RESULTS: The study included 655 patients, 628 (95.88%) with successful retroflexion (mean age: 62.5±10.8 years, 332 male). Indications for colonoscopy were screening in 33.28%, follow up in 36.03%, and diagnostic assessment in 30.69%. In total, 286 polyps and 220 adenomas were detected in the AC. Phase 1 identified 119 adenomas, yielding an adenoma detection rate (ADR) in the AC of 14.2% (95% confidence interval [CI] 11.52-16.84%) while phase 2 identified 86 additional adenomas, improving the ADR in the AC to 22.75% (95%CI 19.54-25.96%; P<0.01). Adenoma miss rate was 39.1% (86/225) and per-patient adenoma miss rate was 11.15% (73/655). Retroflexion proved beneficial mainly in the upper third of the AC (odds ratio [OR] 4.29, 95%CI 1.84-11.56; P<0.01) and for small (<5 mm) adenomas (OR 1.61, 95%CI 1.02-2.56; P=0.04). Multivariate analysis showed that age >60 years, detection of adenomas in forward views and the indication "follow up" influenced ADR during retroflexion. CONCLUSION: Retroflexion is a simple and safe maneuver that increases the ADR in the AC and should complete a second forward view.

Predictors of colorectal cancer screening awareness among people working in a hospital environment.

BACKGROUND: Compliance rates for colorectal cancer (CRC) screening are much lower than those desired. Appropriate information on CRC risks and screening methods is supposed to stimulate motivation for screening. We aimed to identify parameters associated with the decision for CRC screening and colonoscopy in a population expected to have high awareness of disease prevention. METHODS: In a single-center, cross-sectional study, we used an anonymous questionnaire (AQ) to record the demographics, habits and screening behavior for cancers and other common diseases of all employees older than 50 years in our hospital. RESULTS: Among 287 active employees, 83% (n=237) answered the AQ (age 55±4 years). Thirty percent (n=70) underwent colonoscopy while 17% (n=40) underwent CRC screening (39/40) colonoscopy). Comparatively, among women 97% had a Pap-smear, 92% a mammography, while among men 83% had been tested for serum prostate-specific antigen. Age, male sex, alcohol consumption and university education correlated positively with CRC screening (P<0.05 for all). After multivariate analysis, university education remained an independent determinant of CRC screening (OR 2.488, 95%CI 1.096-5.648; P=0.029). Among subjects who had not undergone colonoscopy in the past, ignorance of the need for CRC screening (OR 0.360, 95%CI 0.150-0.867; P=0.023) and indifference to undergo such a procedure (OR 0.188, 95%CI 0.066-0.537; P=0.002) were independent determinants for not planning a future screening colonoscopy. CONCLUSIONS: Education was the most important factor in the decision to undergo CRC screening. Colonoscopy was the preferred screening method. Ignorance of and indifference to CRC risks were the major obstacles for a future screening colonoscopy.