Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial.

BACKGROUND & AIMS: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab. METHODS: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine. Patients in steroid-free clinical remission for ≥6 months and endoscopic remission/improvement (Mayo endoscopic subscore ≤1) were randomized 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 vedolizumab trough concentrations. Secondary outcomes were clinical relapse (partial Mayo score ≥3 and fecal calprotectin >150 µg/g or increase in Mayo endoscopic subscore ≥1 from baseline), fecal calprotectin remission (<150 µg/g), C-reactive protein remission (<5 mg/L), centrally read endoscopic remission (Mayo endoscopic subscore = 0), histologic remission (Nancy index = 0), histo-endoscopic remission, and adverse events. RESULTS: In total, 62 patients were randomized to continue (n = 20) or withdraw (n = 42) thiopurine. At week 48, vedolizumab trough concentrations were not significantly different between continue and withdrawal groups (14.7 µg/mL, interquartile rate [IQR], 12.3-18.5 µg/mL versus 15.9 µg/mL, IQR, 10.1-22.7 µg/mL, respectively, P = 0.36). The continue group had significantly higher fecal calprotectin remission (95.0%, 19/20 versus 71.4%, 30/42; P = .03), histologic remission (80.0%, 16/20 versus 48.6%, 18/37; P = .02), and histo-endoscopic remission (75.0%, 15/20 versus 32.4%, 12/37; P = .002) than the withdrawal group. Histologic activity (hazard ratio [HR], 15.5; 95% confidence interval [CI], 1.6-146.5; P = .02) and prior anti-tumor necrosis factor exposure (HR, 6.5; 95% CI, 1.3-33.8; P = .03) predicted clinical relapse after thiopurine withdrawal. CONCLUSIONS: Thiopurine withdrawal did not affect vedolizumab trough concentrations. However, it may increase fecal calprotectin, histologic, and histo-endoscopic activity. Histologic activity and prior anti-tumor necrosis factor exposure may predict disease relapse on thiopurine withdrawal for patients using vedolizumab for UC. Australian and New Zealand Trial Registry, number ACTRN12618000812291.

Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

AIMS AND OBJECTIVES: To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. BACKGROUND: The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. DESIGN: Multi-site cross-sectional survey. METHODS: An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. RESULTS: Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. CONCLUSION: While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. RELEVANCE TO CLINICAL PRACTICE: Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus-related clinical practice and for the delivery of care and nursing education to people receiving hepatitis B virus anti-viral therapy and at risk of developing hepatocellular carcinoma.

Factors associated with non-adherence to HBV antiviral therapy.

BACKGROUND: HBV antiviral therapy has the potential to reduce the burden of HBV-related liver disease by suppressing HBV DNA replication to undetectable levels, reducing the progression of liver fibrosis and reducing the risk of hepatocellular carcinoma (HCC) development. Treatment outcomes and long-term benefits require adherence to medication regimens. This study aimed to identify the prevalence and factors associated with non-adherence to antiviral therapy. METHODS: A cross-sectional survey of patients receiving HBV antiviral therapies was conducted in three Sydney hospitals. Participants were asked to complete an online questionnaire. Logistic regression was used to assess the associations between non-adherence (defined as missing more than 1 day of medication in the last 30 days) and demographic, socio-economic, disease, treatment, health-care system and individual-related factors. RESULTS: Of the 277 participants, 66 (23.8%) were non-adherent, missing a mean 1.7 days of medication (sd 4.8) in the last 30 days. In multivariate analysis, non-adherent behaviour declined with age (odds ratio [OR] 0.9, 95% CI 0.97, 0.99; P<0.013). Participants who reported having no established routine to take their medication (OR 5.0, 95% CI 1.4, 17.4; P<0.012) and having inadequate health literacy (OR 2.7, 95% CI 1.3, 5.5; P<0.007) were more likely to be non-adherent. CONCLUSIONS: Almost a quarter of participants in the current study were non-adherent. Adherence is potentially modifiable through person-centred education, collaborative models of patient care and interventions designed to improve health literacy and establish medication routines. Findings have the potential to improve health service delivery to patients at risk of non-adherence to HBV antiviral therapy.

Full-Spectrum Endoscopy Improves Surveillance for Dysplasia in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) increase the risk of colorectal cancer. Surveillance colonoscopy with chromoendoscopy is recommended, but conventional forward-viewing colonoscopy (FVC) detects dysplasia with low levels of sensitivity. Full-spectrum endoscopy (FUSE) incorporates 2 additional lateral cameras to the forward camera of the colonoscope, allowing endoscopists to view behind folds and in blind spots, which might increase dysplasia detection. We compared FUSE vs FVC in the detection of dysplasia in patients with IBDs. METHODS: We performed a prospective, randomized, cross-over, tandem colonoscopy study comparing FVC vs FUSE in 52 subjects with IBD undergoing surveillance for neoplasia in Australia (23 with Crohn's colitis, 29 with ulcerative colitis; median age, 45.0 y; 60% male; mean IBD duration, 16.4 y). All subjects met national IBD surveillance inclusion criteria; 27 were assigned randomly to groups that underwent FVC followed by FUSE, and 25 were assigned to groups that underwent FUSE followed by FVC. All procedures were performed from February 2014 through December 2015. Random biopsy specimens were collected and visible lesions were collected; all were analyzed histologically. The primary end point was dysplasia missed by the first colonoscopy detected by the second colonoscopy. Dysplasia was diagnosed by an expert gastrointestinal pathologist blinded to the colonoscope allocation in consensus with a second expert pathologist. RESULTS: FVC missed 71.4% of dysplastic lesions per lesion whereas FUSE missed 25.0% per lesion (P = .0001); FVC missed 75.0% of dysplastic lesions per subject and FUSE missed 25.0% per subject (P = .046). FUSE identified a mean of 0.37 dysplastic lesions and FVC identified a mean of 0.13 dysplastic lesions (P = .044). The total colonoscopy times were similar (21.2 min for FUSE vs 19.1 min for FVC; P = .32), but withdrawal time was significantly longer for FUSE (15.8 min) than for FVC (12.0 min) (P = .03). Correcting for per-unit withdrawal time, the mean dysplasia miss rate per subject was significantly lower for FUSE (0.19) than for FVC (0.83; P < .0001). Targeted tissue acquisition identified significantly more dysplastic lesions than random biopsies (P < .0001). CONCLUSIONS: In a prospective cross-over study of IBD patients undergoing surveillance colonoscopy, we found panoramic views obtained by full-spectrum endoscopy increased the number of dysplastic lesions detected, compared with conventional forward-viewing colonoscopy. Trial no: ACTRN12616000047493.

Factors associated with HBV virological breakthrough.

BACKGROUND: Little is known about non-adherence to HBV therapy. This study aimed to investigate the relationship between self-reported missed days of antiviral therapy and HBV virological breakthrough and factors associated with virological breakthrough. METHODS: A cross-sectional survey of 211 HBV patients receiving oral antiviral therapies was undertaken at three tertiary hospitals in Sydney, Australia. Associations between 0 to >6 missed days in the last 30 days and virological breakthrough (defined as >10-fold rise in serum HBV DNA above nadir or after achieving virological response in the last 12 months) were examined. Logistic regression analyses determined the number of missed days most strongly associated with virological breakthrough and the associated factors. We report odds ratios (ORs) and relative risks (RRs). RESULTS: Of the 204, 32 participants (15.6%) had quantifiable HBV DNA levels (>20 IU/ml); 15 (46.8%) of them experienced virological breakthrough. Participants reported never missing medication (n=130, 63.7%) or missing 1 day (n=23, 11.3%), >1 day (n=23, 11.3%), 2-6 days (n=15, 7.3%) and >6 days (n=13, 6.4%). The most discriminating definition of non-adherence was missing >1 day of medication (RR=8.3; OR=10.2, 95% CI 3.1, 33.8, receiver operating characteristic curve 0.76). Factors independently associated with virological breakthrough included non-adherence (OR=9.0, 95% CI 2.5, 31.9) diagnosed with HBV ≤14 years (OR=5.3, 95% CI 1.0, 26.2) and age ≤47 years (OR=5.4, 95% CI 1.1, 26.9). CONCLUSIONS: Results provide an evidence-based definition of non-adherence to inform clinical practice and provide a basis for key patient education messages. Closer monitoring of groups at risk of viral breakthrough is required.