The combination use of inclisiran and statins versus statins alone in the treatment of dyslipidemia in mainland China: a cost-effectiveness analysis.

Objective: Statin is well-established as a classical lipid-lowering drug, and its cost has reduced considerably in the past years. Inclisiran is a new and effective lipid-lowering drug given as a subcutaneous injection at 6-month intervals. This study aims to evaluate the cost-effectiveness of the combination use of inclisiran and statin versus statin alone for dyslipidemia in the mainland China population. Methods: The Markov decision-making model was used, and the clinical data and real-world data were collected at the University of Hong Kong-Shenzhen Hospital (HKU-SZH). Patients with cardiovascular disease (CVD) and blood lipid levels above the target on statin therapy were included as the target population and analyzed for cardiovascular events, future medical expenses, and the calculation made for the total life cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted to evaluate the influence of parameter uncertainty on the base-case analysis results. Results: If inclisiran was priced at Chinese renminbi (RMB) 20,000.00 (USD 2,973.49) per injection, patients in the inclisiran and statin group would incur an incremental cost of RMB 449,233.56 (USD 66,789.60) compared with the statin group, and they would obtain 0.21 more QALYs in their life cycle. The subsequent ICER of RMB 2,127,756.78 (USD 316,343.32)/QALY was significantly higher than the willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China, which was RMB 257,094.00 (USD 38,223.33)/QALY, suggesting that the combined use of inclisiran and statin was not cost-effective. If the price of inclisiran were reduced to RMB 2,500.00 (USD 371.69)/injection, the ICER of patients in the inclisiran and statin group would become RMB 257,790.63 (USD 38,326.91)/QALY, which is slightly lower than the WTP threshold of 3 times the per capita GDP of China, indicating that the combined use of inclisiran and statin would be cost-effective. Conclusion: If inclisiran is priced at RMB 20,000.00 (USD 2,973.49)/injection, then the combined use of inclisiran and statins is not cost-effective compared with statin alone. It will be economical only if the price of inclisiran is reduced by more than 88%.

Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension.

BACKGROUND: For hypertensive patients without a history of stroke or myocardial infarction (MI), the China Stroke Primary Prevention Trial (CSPPT) demonstrated that treatment with enalapril-folic acid reduced the risk of primary stroke compared with enalapril alone. Whether folic acid therapy is an affordable and beneficial treatment strategy for the primary prevention of stroke in hypertensive patients from the Chinese healthcare sector perspective has not been thoroughly explored. METHODS: We performed a cost-effectiveness analysis alongside the CSPPT, which randomized 20,702 hypertensive patients. A patient-level microsimulation model based on the 4.5-year period of in-trial data was used to estimate costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for enalapril-folic acid vs. enalapril over a lifetime horizon from the payer perspective. RESULTS: During the in-trial follow-up period, patients receiving enalapril-folic acid gained an average of 0.016 QALYs related primarily to reductions in stroke, and the incremental cost was $706.03 (4553.92 RMB). Over a lifetime horizon, enalapril-folic acid treatment was projected to increase quality-adjusted life years by 0.06 QALYs or 0.03 life-year relative to enalapril alone at an incremental cost of $1633.84 (10,538.27 RMB), resulting in an ICER for enalapril-folic acid compared with enalapril alone of $26,066.13 (168,126.54 RMB) per QALY gained and $61,770.73 (398,421.21 RMB) per life-year gained, respectively. A probabilistic sensitivity analysis demonstrated that enalapril-folic acid compared with enalapril would be economically attractive in 74.5% of simulations at a threshold of $37,663 (242,9281 RMB) per QALY (3x current Chinese per capita GDP). Several high-risk subgroups had highly favorable ICERs < $12,554 (80,976 RMB) per QALY (1x GDP). CONCLUSIONS: For both in-trial and over a lifetime, it appears that enalapril-folic acid is a clinically and economically attractive medication compared with enalapril alone. Adding folic acid to enalapril may be a cost-effective strategy for the prevention of primary stroke in hypertensive patients from the Chinese health system perspective.

Comparing the measurement properties of the EQ-5D-5L and the EQ-5D-3L in hypertensive patients living in rural China.

PURPOSE: The purpose of this study was to compare the measurement properties of two versions of EQ-5D (i.e.EQ-5D-3L and EQ-5D-5L) in hypertensive patients in rural China. METHODS: A cross-sectional survey was carried out in hypertensive patients in rural China. We compared the ceiling effects, redistribution properties, informativity, known-groups validity, and relative efficiency of the 3L and 5L and examined their agreement. RESULTS: A total of 11,412 patients were enrolled in our study. The mean EQ-5D index score was 0.84 (SD 0.21) according to the 5L and 0.86 (SD 0.17) according to the 3L. A good agreement was observed between the 3L and 5L. The overall ceiling effect decreased from 46.4% (3L) to 29.4% (5L). The Shannon index, H' improved in all dimensions when used 5L. When used 3L, the median responses of all groups were consistent with 5L across the three dimensions of 'mobility', 'self-care', 'usual activities', while the median responses were inconsistent for the 'pain/discomfort' and 'anxiety/depression' dimensions. The 3L performed better in eight comorbidities in terms of F-statistics and six comorbidities in terms of the area under the receiver operating characteristic curves (AUROCs). The 5L performed better both in terms of the F-statistics and AUROCs in age, education level, anti-hypertensive medication use. CONCLUSION: Taking all comparisons into account, we recommend the EQ-5D-5L for use in patients with hypertension in rural China.

Cost-effectiveness of pembrolizumab plus axitinib as first-line therapy for advanced renal cell carcinoma.

Aim: To evaluate the cost-effectiveness of first-line treatments for advanced renal cell carcinoma with pembrolizumab plus axitinib compared with sunitinib from the US payer perspective. Patients & methods: A Markov model was developed for this purpose. The clinical data were obtained from the KEYNOTE-426 trial. Utility values and direct costs related to the treatments were gathered from the published studies. Results: The incremental cost-effectiveness ratios of pembrolizumab plus axitinib versus sunitinib was $249,704 per quality-adjusted life year, which was higher than a willingness-to-pay threshold of $150,000 per quality-adjusted life year. Conclusion: Pembrolizumab plus axitinib was not considered to be cost-effective versus sunitinib as a first-line treatment for patients with advanced renal cell carcinoma from the US payer perspective.

Histamine2-Receptor Antagonists, Proton Pump Inhibitors, or Potassium-Competitive Acid Blockers Preventing Delayed Bleeding After Endoscopic Submucosal Dissection: A Meta-Analysis.

Background: Endoscopic submucosal dissection (ESD) was commonly used for en bloc resection in gastric cancer and adenoma with the risk of delayed bleeding after ESD. We conducted a direct and indirect comparison meta-analysis to evaluate the best choice in preventing post-ESD bleeding among proton pump inhibitors (PPIs), histamine2-receptor antagonists (H2RAs), and the most widely used potassium-competitive acid blocker, vonoprazan. Methods: The Pubmed, Cochrane Library, and Embase were searched for randomized trials. We pooled odds ratios (OR) for preventing post-ESD bleeding using meta-analysis. Results: Sixteen randomized trials met the inclusion criteria including 2,062 patients. Direct comparisons showed slightly significant efficacy in PPIs rather than H2RAs in preventing post-ESD bleeding [OR: 1.83; 95% confidence interval (CI): 1.10 to 3.05] and vonoprazan was better than PPIs (OR: 0.46; 95% CI: 0.25 to 0.86). The adjusted indirect comparison indicated vonoprazan was superior to H2RAs (OR: 0.30, 95% CI: 0.12 to 0.74). In subgroup analysis, PPIs had similar efficacy as H2RAs in 4 weeks, while PPIs were better than H2RAs in 8 weeks' treatment (OR: 1.91; 95% CI: 1.08 to 3.40). The superiority of vonoprazan than PPIs was more significant in combination therapy (OR: 0.18; 95% CI: 0.04 to 0.69). There was a significant difference in vonoprazan for 8 weeks of medication (OR: 0.44; 95% CI: 0.21 to 0.92). Conclusions: The effects of vonoprazan is better than PPIs than H2RAs in preventing bleeding after ESD. When vonoprazan combined with mucosal protective antiulcer drug in treatment or used in 8 weeks of medication, the efficacy may be even better.

Treatment Outcomes in Patients With Newly Diagnosed Multiple Myeloma Who Are Ineligible for Stem-Cell Transplantation: Systematic Review and Network Meta-analysis.

Many new regimens have been applied to newly diagnosed transplant-ineligible multiple myeloma, but no head-to-head research has been performed to compare the efficacy of these treatments. Currently lenalidomide plus dexamethasone (Rd) is one of the standard treatments. Our aim was to make a comparison of these treatments to Rd by a network meta-analysis. We performed a systematic review and network meta-analysis. We searched PubMed, Embase, and the Cochrane Library for articles published from January 1, 1988, to April 26, 2018, as well as research presented at 5 international conferences (American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, European Society of Medical Oncology, and International Myeloma Working Group) between January 2015 and December 2018. Our interest outcomes were hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS). Bayesian fixed-effects mixed-treatment comparisons were used for this study. A total of 23 articles describing 10,401 participants were included for this network meta-analysis. Lenalidomide and dexamethasone plus daratumumab (HR, 0.57; 95% credible interval [CrI], 0.43-0.73), daratumumab plus bortezomib, melphalan, and prednisone (HR, 0.59; 95% CrI, 0.36-0.91), and the combination of bortezomib with lenalidomide and dexamethasone (RVd) (HR, 0.72, 95% CrI, 0.56-0.90) all showed significant effect compared to Rd for PFS. RVd demonstrated significant benefit compared to Rd (HR, 0.72; 95% CrI, 0.53-0.96) for OS. Our study results suggested that lenalidomide and dexamethasone plus daratumumab; daratumumab plus bortezomib, melphalan, and prednisone; and RVd showed better efficacy than Rd in PFS; and RVd showed better efficacy than Rd in OS in patients with newly diagnosed transplant-ineligible multiple myeloma in the absence of head-to-head research.

Health-related quality of life among rural men and women with hypertension: assessment by the EQ-5D-5L in Jiangsu, China.

PURPOSE: Hypertension is a major global public health problem, including rural China. However, studies examining health-related quality of life (HRQoL) for patients with hypertension have been mostly conducted in urban populations. This study aimed to use the EuroQol five-dimensional-five-level (EQ-5D-5L) and its recently developed Chinese value set to analyze HRQoL and its influencing factors among hypertensive population in rural China. METHODS: This is a cross-sectional population-based survey. Standard interview of participants was conducted from July to September 2016 in Donghai County's 334 villages of Jiangsu Province, China. Data collection included the EQ-5D-5L, along with sociodemographic characteristics and disease-related factors such as duration of hypertension, antihypertensive treatment and comorbid conditions. The Tobit regression model was employed to analyze potential influencing factors on HRQoL. RESULTS: A total of 16,596 adults (18 years and older) with hypertension participated in this study. 62.4% were women. The mean utility score was 0.85 (standard deviation [SD] = 0.23). The proportion of participants reporting pain/discomfort problems was highest, while least patients reported problems in self-care dimension. Females, elderly, illiterate patients, ex-smokers and patients with longer duration of hypertension or comorbidities scored lower on HRQoL than others. Stroke, heart failure and coronary heart disease were associated with a larger negative impact on HRQoL among all comorbidities. CONCLUSIONS: The HRQoL was lower in this rural hypertensive population than previously reported urban counterparts. To improve the HRQoL of hypertensive patients in rural areas, it is important to control hypertension and prevent its associated co-morbidities. More attention needs to be directed to elderly female patients with less education who scored much lower HRQoL than their male counterparts.

Ixazomib - the first oral proteasome inhibitor.

Ixazomib, as a proteasome inhibitor, inhibits the chymotrypsin-like activity of the ß5 subunit of the 20S proteasome. Based on the TOURMALINE-MM1 study, ixazomib was proved by the FDA as the orphan drug in November 2015. With a promising effect in prolonging the progression-free survival compared with placebo treatment (median: 20.6 versus 14.7 months), it was the first oral compound combined with lenalidomide and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior therapy. The main adverse events include low-grade hematological, digestive, or cutaneous events, which were manageable with care. Overall, ixazomib demonstrated favorable safety profile. Ongoing trials are conducted to define its place in first-line, maintenance, and relapse therapies. In this review, we summarized the clinical pharmacology, efficacy, tolerability, safety, and cost-effectiveness of ixazomib.

Comparison of Oral Antidiabetic Drugs as Add-On Treatments in Patients with Type 2 Diabetes Uncontrolled on Metformin: A Network Meta-Analysis.

We assessed the efficacy and safety of oral antidiabetic drugs (OADs) as an add-on treatment in patients with type 2 diabetes uncontrolled on metformin. PubMed, the Cochrane Library, and Embase were searched from inception to October 20, 2017. Pairwise and network meta-analyses were conducted using Stata 14.1 software. Odds ratios (ORs) and weighted mean differences (WMDs) were used to evaluate outcomes. Sixty-eight trials including 36,746 patients were analyzed. No significant differences in the risk of major adverse cardiovascular events (MACEs) and all-cause mortality were observed among any class of OADs when combined with metformin. All classes of OADs as add-ons to metformin improved glucose control, while sodium-glucose co-transporter-2 (SGLT-2) inhibitors showed greater fasting plasma glucose (FPG) reductions {WMD, - 1.49 [95% confidence interval (CI) - 1.69 to - 1.28] mmol/l} and 2 h postprandial glucose (2 h PPG) reductions [WMD, - 3.07 (95% CI - 4.12 to - 2.03) mmol/l]. Thiazolidinediones and sulfonylureas were associated with weight gain [WMD, 2.53 (95% CI 1.95-3.10) kg and 2.00 (95% CI 1.63-2.36) kg, respectively] when added to metformin. Sulfonylureas [WMD, 6.52 (95% CI 4.07-10.45)] were associated with the highest ORs of hypoglycemia. Our results suggest that the seven classes of OADs were not associated with any increased risk of MACEs or all-cause mortality when combined with metformin. Most OADs were associated with similarly large reductions in HbA1c levels when added to metformin, while SGLT-2 inhibitors might be the best option for reducing body weight, FPG, and 2-h PPG.

Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis.

AIMS: This study aimed to investigate the efficacy and safety of dual therapy comprising sulfonylurea (SU) plus antidiabetic drugs for the treatment of type 2 diabetes mellitus (T2DM). METHODS: We searched the PubMed, Cochrane library, and Embase databases for randomized clinical trials (≥24 weeks) published up to December 28, 2017. Subsequently, we conducted pairwise and network meta-analyses to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) of the outcomes. RESULTS: The final analyses included 24 trials with a total of 10,032 patients. Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)]. Notably, the combination of SU plus glucagon-like peptide-1 receptor agonist (GLP-1RA) was associated with the most significant increase in the risk of hypoglycemia. Furthermore, all SU-based combination regimens reduced the glycated hemoglobin (HbA1c) and fasting plasma glucose levels (FPG). However, only combinations containing SGLT-2i [MD, -1.00 kg (95% CI: -1.73 to -0.27)] and GLP-1RA [MD, -0.56 kg (95% CI: -1.10 to -0.02)] led to weight loss. CONCLUSIONS: Our findings highlight the importance of considering the risk of hypoglycemia when selecting antidiabetic drugs to be administered concomitantly with SU. Although all classes of antidiabetic drugs improved glucose control when administered in combination with SU, SGLT-2i might be the best option with respect to factors such as hypoglycemia and body weight.

Systematic review and meta-analysis of the efficacy and safety of novel monoclonal antibodies for treatment of relapsed/refractory multiple myeloma.

Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%). mAb-based regimens prolonged progression-free survival (PFS, hazard ratio: 0.52, 95% CI: 0.36-0.75) compared to non-mAb-based regimens. Additionally, the efficacy of triplet regimens was superior to that of single or doublet regimens. The same trend was observed in a subgroup analysis of daratumumab and elotuzumab. The most common grade 3/4 adverse events included neutropenia, lymphopenia, thrombocytopenia, anemia, leukopenia, pneumonia, and fatigue. Elotuzumab and daratumumab improved the ORR, at least VGPR, and PFS compared to non-mAb-based regimens. In a pooled analysis, both mAbs had promising efficacy and safety profiles, particularly in triplet regimens. The same trend was observed in daratumumab- and elotuzumab-based regimens. Daratumumab triplet therapy (daratumumab, lenalidomide, and dexamethasone) was superior to other triplet regimens for the treatment of RRMM, and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients, suggesting CD38 is an effective target for treatment of RRMM. Additional clinical studies of elotuzumab and daratumumab will be required to validate these results.