Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir for HCV NS5A-inhibitor experienced patients with difficult to cure characteristics

Abstract Background In clinical trials, 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 four serious AEs including one death and three hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. Conclusion 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.

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Unresectable hepatocellular carcinoma: prospects for drug therapy with lenvatinib

Malignant tumours ◽

10.18027/2224-5057-2021-11-3-45-52 ◽

2022 ◽

Vol 11 (3) ◽

pp. 45-52

Author(s):

V. V. Breder ◽

D. T. Abdurakhmanov ◽

V. V. Petkau ◽

P. V. Balakhnin ◽

M. V. Volkonsky ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Drug Therapy ◽

Liver Function ◽

Real World ◽

Systemic Therapy ◽

Efficacy And Safety ◽

Study Results ◽

Class B ◽

Pugh Class ◽

Positive Results

There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.

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Efficacy and Safety of Bevacizumab in Combination with Chemotherapy for Colorectal Cancer – A Real World Study in China

10.21203/rs.3.rs-29014/v1 ◽

2020 ◽

Author(s):

Tao Shen ◽

Xian-Shuo Cheng ◽

Wei-Xun Chunyu ◽

Hong-Tao Zhang ◽

Cui-Feng Xia ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Real World ◽

Large Scale ◽

Progression Free Survival ◽

Secondary Outcome ◽

Second Line ◽

Efficacy And Safety ◽

First Line ◽

Demographic Subgroups

Abstract Background Large scale randomized trials have demonstrated that bevacizumab in addition to chemotherapy as first-line or second-line treatment has significant survival benefits. We aim to explore the clinical impact of bevacizumab in combination with chemotherapy in first-line or second-line in patients with colorectal cancer (CRC). Methods The medical records of patients with CRC who received bevacizumab at first or second-line of treatment were collected retrospectively. The primary outcome of the study was to evaluate the efficacy of bevacizumab in combination with chemotherapy by survival endpoints i.e. overall survival (OS) and progression-free survival (PFS) and the secondary outcome was to evaluate its safety by incidence of adverse events (AE). Results Fifty-one patients with CRC had met the selection criteria for treatment with bevacizumab to either cetuximab or FOLFOX or both. The median age was 54 years. During follow-up, ten patients had exhibited progression after treatment while 5 patients died. The median OS and PFS of the overall population were not reached. The Cox proportional regression analysis revealed no significant prognostic factors of OS and PFS for treatment with bevacizumab in various demographic subgroups. The 1-year PFS rates of all 51 patients was 76%. The 1-year and 3-year OS rates for all 51 patients were 95% and 88%, respectively. Toxicities were usually mild in nature, with nausea, vomiting, hand and foot syndrome, neutropenia, asthenia and palpitation being the commonly reported adverse events. Conclusion In this real-world setting, the efficacy and safety of bevacizumab in combination with chemotherapy is limited and further research is warranted as to whether bevacizumab with chemotherapy is an optimal treatment as first-line or second-line therapy in Chinese CRC patients.

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IDDF2021-ABS-0167 Real-world efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir in NS5A-inhibitor experienced patients: an international multicenter study from Asia

10.1136/gutjnl-2021-iddf.99 ◽

2021 ◽

Author(s):

Yu Jun Wong ◽

Rajneesh Kumar ◽

Chen Hua Liu ◽

Jia Horng Kao ◽

Vicky Wing-Ki Hui ◽

...

Keyword(s):

Multicenter Study ◽

Real World ◽

Efficacy And Safety ◽

Ns5a Inhibitor ◽

International Multicenter Study ◽

International Multicenter

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To compare the efficacy and safety of silodosin and dutasteride combination with alfuzosin and dutasteride combination in patients of benign prostatic hyperplasia: a randomized, open label study

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20191095 ◽

2019 ◽

Vol 8 (4) ◽

pp. 635

Author(s):

Iram Kahkashan ◽

Shabnam Chawdhary ◽

Vishal R. Tandon ◽

Rahul Gupta

Keyword(s):

Flow Rate ◽

Urine Volume ◽

Maximum Flow ◽

Drug Combinations ◽

Secondary Outcome ◽

Efficacy And Safety ◽

Open Label ◽

Treatment Groups ◽

Intention To Treat ◽

Group 2

Background: BPH is a major cause of bothersome lower urinary tract symptoms (LUTS) and affects quality of life (QoL) which deteriorates if not taken care with the passage of time. The aim and objective of the study was to compare the efficacy and safety of combination of silodosin and dutasteride with the combination of alfuzosin and dutasteride in patients of BPH.Methods: A randomized, open label, intention to treat study was carried out on newly diagnosed patients of BPH. Patients were randomly divided into two groups and followed up to 12 weeks. Group 1 of patients received a combination of silodosin 8 mg and dutasteride 0.5 mg (SD) (n=20) while the patients of group 2 received combination of alfuzosin 10 mg and dutasteride 0.5 mg (AD) (n=20). Primary endpoint was measured by changes in the mean baseline International prostate symptom score (I-PSS) and uroflowmetry and secondary outcome with changes observed on ultrasonography.Results: IPSS and IPSS-QOL significantly improved in both the treatment groups (p <0.001) along with mean maximum flow rate (Qmax) and mean average flow rate (Qavg). Prostate volume and residual urine volume showed a significant improvement in both the treatment groups at 12 weeks. However, the intergroup differences in IPSS, uroflowmetry and USG parameters were not significant. Both treatments were well tolerated.Conclusions: The current study established that both the drug combinations i.e. silodosin and dutasteride (SD) and alfuzosin and dutasteride (AD) largely have a comparable effect on both the dynamic and static components of BPH. Further, both drug combinations appear to have a comparable safety profile.

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Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽

10.1024/0301-1526/a000746 ◽

2019 ◽

Vol 48 (2) ◽

pp. 134-147 ◽

Cited By ~ 8

Author(s):

Mirko Hirschl ◽

Michael Kundi

Keyword(s):

Real World ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Efficacy And Safety ◽

Nonvalvular Atrial Fibrillation ◽

Real World Data ◽

Hazard Ratios ◽

Direct Acting ◽

Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

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