Ibrutinib versus bendamustine plus rituximab for first-line treatment of 65 or older patients with untreated chronic lymphocytic leukemia without del(17p)/TP53 mutation in China: a lifetime economic research study.

BACKGROUND: The incidence and mortality rates of patients with chronic lymphocytic leukemia (CLL) in China have recently increased. This study performed a long-term economic evaluation of the first-line treatment strategies ibrutinib (IB) or bendamustine (BE) plus rituximab (RI) for previously untreated older patients with CLL without the del(17p)/TP53 mutation in China. METHODS: Based on clinical data from large, randomized trials, a Markov model including four disease states (event-free survival, treatment failure, post-treatment failure, and death) was used to estimate the incremental costs per quality adjusted-life year (QALY) gained from the first-line IB strategy versus the BE plus RI strategy over a 10-year period. All costs were adjusted to 2022 values based on the Chinese Consumer Price Index, and all costs and health outcomes were discounted at an annual rate of 5%. Sensitivity analysis was performed to confirm the robustness of base-case results. RESULTS: Compared to the first-line BE plus RI strategy, first-line IB treatment achieved 1.17 additional QALYs, but was accompanied by $88,046.78 (estimated in 2022 US dollars) in decremental costs per patient over 10 years. Thus, first-line treatment with IB appeared to have absolute dominance compared to the BE plus RI strategy. Sensitivity analysis confirmed the robustness of these results. CONCLUSIONS: The first-line treatment with IB is absolutely cost-effective compared to the first-line BE plus RI treatment strategy for 65 or older patients with CLL without the del (17p)/TP53 mutation from the Chinese payer perspective. Therefore, it is strongly recommended that Chinese health authorities select the former strategy for these CLL patients.

A lifetime economic research of universal HLA-B*58:01 genotyping or febuxostat initiation therapy in Chinese gout patients with mild to moderate chronic kidney disease.

OBJECTIVE: To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system. METHODS: A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed. RESULTS: Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results. CONCLUSION: From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China's health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.

The economic research of arsenic trioxide for the treatment of newly diagnosed acute promyelocytic leukemia in China.

BACKGROUND: The objective of this study was to conduct the first systematic evaluation of the long-term economic impact of arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) from the perspective of the Chinese health care system. METHODS: On the basis of clinical data from a randomized phase 3 trial, a time-dependent Markov model with 4 health states (complete remission, relapse or treatment failure, post-treatment failure, and death) was used to evaluate the incremental costs per quality-adjusted life-year (QALY) gained from the ATO plus ATRA regimen compared with the ATRA plus chemotherapy (CT) regimen over a 30-year period. All costs were adjusted to 2018 levels based on the Chinese Consumer Price Index. Both costs and health outcomes were discounted by 3% annually. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: Compared with the ATRA plus CT strategy, the ATO plus ATRA strategy was associated with 1.38 additional QALYs gained and $392.05 (estimated in 2018 US dollars) in incremental costs per patient over 30 years. Consequently, the incremental cost-effectiveness ratio was $284.02 per QALY gained, which was far below the Chinese willingness-to-pay threshold of $29,306 per QALY gained. Sensitivity analyses demonstrated the robustness of these results. CONCLUSIONS: From the perspective of the Chinese health care system, the ATO plus ATRA strategy is cost-effective for patients with newly diagnosed APL compared with the ATRA plus CT strategy. Therefore, the authors strongly suggest that China's health authorities choose the former strategy for these patients, whether for the elderly or for young people.

Concurrent chemoradiotherapy comparison of taxanes and platinum versus 5-fluorouracil and platinum in nasopharyngeal carcinoma treatment.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma especially prevailing among the natives of southern China. The regimen of concurrent chemoradiotherapy (CCRT) that include platinum and 5-fluorouracil (5-FU) is considered to be the standard treatment for NPC. However, its clinical use is limited by its toxicity. Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment. METHODS: Medline, the Cochrane library, and the Chinese medical literature database were searched for eligible studies. Meta-analysis was performed using Review Manager (Version 5.2). RESULTS: Six random controlled trials (RCTs) including 514 patients met our criteria. Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission (CR) and less incidence rate in adverse reactions such as gastrointestinal impairment grades III-IV, liver and kidney impairment grades I-II, and radiodermatitis grades III-IV versus the conventional regimen of CCRT with 5-FU and platinum, while the longterm effectiveness rate of overall survival, locoregional failure-free survival, or distant metastasis failure-free survival between the two groups was therapeutic equivalence. CONCLUSIONS: The regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT. However, we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare, analyze, and confirm the findings.

Upregulation of microRNA-1 and microRNA-133 contributes to arsenic-induced cardiac electrical remodeling.

BACKGROUND: A large body of evidence showed that arsenic trioxide (As2O3), a front-line drug for the treatment of acute promyelocytic leukemia, induced abnormal cardiac QT prolongation, which hampers its clinical use. The molecular mechanisms for this cardiotoxicity remained unclear. This study aimed to elucidate whether microRNAs (miRs) participate in As2O3-induced QT prolongation. METHODS: A guinea pig model of As2O3-induced QT prolongation was established by intravenous injection with As2O3. Real-time PCR and Western blot were employed to determine the expression alterations of miRs and mRNAs, and their corresponding proteins. RESULTS: The QT interval and QRS complex were significantly prolonged in a dose-dependent fashion after 7-day administration of As2O3. As2O3 induced a significant upregulation of the muscle-specific miR-1 and miR-133, as well as their transactivator serum response factor. As2O3 depressed the protein levels of ether-a-go-go related gene (ERG) and Kir2.1, the K(+) channel subunits responsible for delayed rectifier K(+) current IKr and inward rectifier K(+) current IK1, respectively. In vivo transfer of miR-133 by direct intramuscular injection prolonged QTc interval and increased mortality rate, along with depression of ERG protein and IKr in guinea pig hearts. Similarly, forced expression of miR-1 widened QTc interval and QRS complex and increased mortality rate, accompanied by downregulation of Kir2.1 protein and IK1. Application of antisense inhibitors to knockdown miR-1 and miR-133 abolished the cardiac electrical disorders caused by As2O3. CONCLUSIONS: Deregulation of miR-133 and miR-1 underlies As2O3-induced cardiac electrical disorders and these miRs may serve as potential therapeutic targets for the handling of As2O3 cardiotoxicity.

L-type calcium current (ICa,L) and inward rectifier potassium current (IK1) are involved in QT prolongation induced by arsenic trioxide in rat.

The present study was designed to study the effects of As(2)O(3) on QT interval prolongation and to explore the potential ionic mechanisms in isolated rat ventricular cardiomyocytes. The rats of As(2)O(3) group were treated with 0.8 mg·kg(-1)·d(-1) As(2)O(3) intravenously for 7 days consecutively and the control group with saline. The ECG was recorded to calculate heart rate-corrected QT interval (QTc). Single cardiomyocytes were isolated by using collagenase II, and the action potential duration (APD) and ion currents were recorded by whole-cell patch clamp. [Ca(2+)](i) was examined by confocal laser scanning microscopy. Our data showed that both QTc and APD were prolonged significantly after As(2)O(3)treatment. Meanwhile, As(2)O(3) suppressed I(K1) and shifted the reversal potential to more positive direction. Moreover, the density of I(Ca,L) was augmented significantly, and the steady-state activation curve became more negative, whereas, the inactivation and reactivation of I(Ca,L) were not changed notably after As(2)O(3) administration. Furthermore, the maximal [Ca(2+)](i) was enhanced obviously by either KCl or caffeine stimulation in As(2)O(3)-treated cardiomyocytes. Our results show that the potential mechanism of As(2)O(3)-induced QT interval prolongation in rat might be relative to disturbing the fine balance of transmembrane currents (increasing I(Ca,L) and decreasing I(K1)) and causing APD prolongation.