Background We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe COVID-19 using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard-of-care. Methods GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed SARS-CoV-2 infection, were hospitalized, had oxygen saturation 94% or lower on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard-of-care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. Results After the inverse probability of treatment weighting procedure 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio 2.03: 95% confidence interval 1.34–3.08, p<0.001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (adjusted odds ratio 0.38, 95% confidence interval: 0.22–0.68, p=0.001). Conclusions In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19.

Background Remdesivir is FDA approved for the treatment of hospitalized patients with COVID-19 and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials. Methods This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (non-remdesivir cohort). Eligible patients, aged ≥18 years, had confirmed SARSCoV-2, oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints). Results Altogether, 368 (remdesivir) and 1399 (non-remdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the non-remdesivir cohort (65.2% vs 57.1%; OR 1.49, 95% CI 1.16–1.90; P = .002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the non-remdesivir cohort (12.0% vs 16.2%; OR 0.67, 95% CI 0.47–0.95; P = .03). Conclusions Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. Collectively, these data support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.

SummaryBackgroundIt is controversial whether chronic hepatitis B (CHB) patients have more non‐liver comorbidities than non‐CHB subjects.AimTo characterise the demographics, comorbidity and health utilisation of CHB patients in South Korea and compare them to matched controls.MethodsUsing the Health Insurance Review & Assessment Service (HIRA) 2007‐2016 database, adult patients with claims for CHB analysed. CHB cases and non‐CHB controls matched in a 1:4 ratio using propensity score matching method.ResultsThe age of CHB patients significantly increased from a mean 46.9 years in 2007 to 52.3 years in 2016. The proportions of persons having both liver‐related and non‐liver related comorbidities were higher in CHB patients compared to matched controls (dyslipidaemia [37.23% vs 23.77%, P < 0.0001], hypertension [29.39% vs 25.27%, P < 0.0001] chronic kidney disease (CKD) [3.02% vs 1.14%, P < 0.0001] and osteoporosis/fracture [OF] [4.09% vs 3.23%, P < 0.0001]). Approximately 50% of CHB patients had more than one comorbidity among CKD, diabetes, DLP, and OF. The odds of CKD in CHB patients were 1.42 times higher, and the odds of OF in CHB patients were 1.09 times higher than matched controls after adjustment for confounders (P < 0.0001).ConclusionPrevalence of liver as well as non‐liver comorbidities in patients with CHB was higher than matched controls and increased over time.

Aims: Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. Methods: An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria. Results: Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%-20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients. Conclusion: Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.

Background This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Methods We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a “NASH” subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests. Results 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p < 0.001 for 2011 vs 2017). Mean total all-cause healthcare costs ranged from ¥322,206 to ¥340,399 per patient per year between 2011 and 2017. Although total all-cause healthcare costs did not change significantly (p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population. Conclusions There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.