Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients With Difficult to Cure Characteristics.

BACKGROUND: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSIONS: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Prospective population-based cohort of inflammatory bowel disease in the biologics era: Disease course and predictors of severity.

BACKGROUND AND AIM: We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population-based registry was established to assess disease severity, frequency of complications, and prognostic factors. METHODS: Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use. RESULTS: We report on the early outcomes (median 18 months, range 12-60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P < 0.05). Twenty-four percent of UC patients were hospitalized, most within the first 12 months. Intestinal resection rates were 13% at 1 year in CD and 26% at 5 years. Risk factors include penetrating and stricturing disease (P < 0.001) and ileal involvement (P < 0.05). Colectomy rates in UC were 2% and 13% at 1 and 5 years. High C-reactive protein (CRP) at diagnosis was associated with colectomy. CONCLUSIONS: A high rate of inflammatory disease, frequent immunomodulator use in CD, and a low rate of surgery in both CD and UC were identified. In CD, ileal involvement and complex disease behavior are associated with a more severe disease course, while in UC a high CRP predicted this outcome.

Health Care Cost Analysis in a Population-based Inception Cohort of Inflammatory Bowel Disease Patients in the First Year of Diagnosis.

BACKGROUND: There are limited prospective population-based data on the health care cost of IBD in the post-biologicals era. A prospective registry that included all incident cases of inflammatory bowel disease [IBD] was established to study disease progress and health cost. AIM: To prospectively assess health care costs in the first year of diagnosis among a well-characterised cohort of newly diagnosed IBD patients. METHOD: Incident cases of IBD were prospectively identified in 2007-2008 and 2010-2013 from multiple health care providers, and enrolled into the population-based registry. Health care resource utilisation for each patient was collected through active surveillance of case notes and investigations including specialist visits, diagnostic tests, medications, medical hospitalisation, and surgery. RESULTS: Off 276 incident cases of IBD, 252 [91%] were recruited to the registry, and health care cost was calculated for 242 (146 Crohn's disease [CD] and 96 ulcerative colitis [UC] patients). The median cost in CD was higher at A$5905 per patient (interquartile range [IQR]: A$1571-$91,324) than in UC at A$4752 [IQR: A$1488-A$58,072]. In CD, outpatient resources made up 55% of all cost, with medications accounting for 32% of total cost [15% aminosalicylates, 15% biological therapy], followed by surgery [31%], and diagnostic testing [21%]. In UC, medications accounted for 39% of total cost [of which 37% was due to 5-aminosalicylates, and diagnostics 29%; outpatient cost contributed 71% to total cost. CONCLUSION: In the first year of diagnosis, outpatient resources account for the majority of cost in both CD and UC. Medications are the main cost driver in IBD.