Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis
Health technology assessment (Winchester, England). 2020;24(51):1-220
BACKGROUND There have been no licensed treatment options in the UK for treating thrombocytopenia in people with chronic liver disease requiring surgery. Established management largely involves platelet transfusion prior to the procedure or as rescue therapy for bleeding due to the procedure. OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of two thrombopoietin receptor agonists, avatrombopag (Doptelet(®); Dova Pharmaceuticals, Durham, NC, USA) and lusutrombopag (Mulpleta(®); Shionogi Inc., London, UK), in addition to established clinical management compared with established clinical management (no thrombopoietin receptor agonist) in the licensed populations. DESIGN Systematic review and cost-effectiveness analysis. SETTING Secondary care. PARTICIPANTS Severe thrombocytopenia (platelet count of < 50,000/µl) in people with chronic liver disease requiring surgery. INTERVENTIONS Lusutrombopag 3 mg and avatrombopag (60 mg if the baseline platelet count is < 40,000/µl and 40 mg if it is 40,000-< 50,000/µl). MAIN OUTCOME MEASURES Risk of platelet transfusion and rescue therapy or risk of rescue therapy only. REVIEW METHODS Systematic review including meta-analysis. English-language and non-English-language articles were obtained from several databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, all searched from inception to 29 May 2019. ECONOMIC EVALUATION Model-based cost-effectiveness analysis. RESULTS From a comprehensive search retrieving 11,305 records, six studies were included. Analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy or rescue therapy only, and mostly with a statistically significant difference (i.e. 95% confidence intervals not overlapping the point of no difference). However, only avatrombopag seemed to be superior to no thrombopoietin receptor agonist in reducing the risk of rescue therapy, although far fewer patients in the lusutrombopag trials than in the avatrombopag trials received rescue therapy. When assessing the cost-effectiveness of lusutrombopag and avatrombopag, it was found that, despite the success of these in avoiding platelet transfusions prior to surgery, the additional long-term gain in quality-adjusted life-years was very small. No thrombopoietin receptor agonist was clearly cheaper than both lusutrombopag and avatrombopag, as the cost savings from avoiding platelet transfusions were more than offset by the drug cost. The probabilistic sensitivity analysis showed that, for all thresholds below £100,000, no thrombopoietin receptor agonist had 100% probability of being cost-effective. LIMITATIONS Some of the rescue therapy data for lusutrombopag were not available. There were inconsistencies in the avatrombopag data. From the cost-effectiveness point of view, there were several additional important gaps in the evidence required, including the lack of a price for avatrombopag. CONCLUSIONS Avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy, but they were not cost-effective given the lack of benefit and increase in cost. FUTURE WORK A head-to-head trial is warranted. STUDY REGISTRATION This study is registered as PROSPERO CRD42019125311. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 51. See the NIHR Journals Library website for further project information.
Cost-utility of new film-coated tablet formulation of deferasirox vs deferoxamine among major beta-thalassemia patients in Iran
Medicine (Baltimore). 2020;99(28):e20949
OBJECTIVES Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox (Jadenu) vs deferoxamine (Desferal) among B-Thalassemia-major patients from payer perspective in Iran. METHODS An economic-evaluation through Markov model was performed. A systematic review was conducted in order to evaluate the clinical effectiveness of comparators. Because of chelating therapy is weight-dependent, patients were assumed to be 2 years-old at initiation in first and 18 years-old in second scenario, and model was estimated lifetime costs and utilities. Costs were calculated to the Iran healthcare system through payer perspective and measured effectiveness using quality-adjusted life years (QALYs). One-way sensitivity analysis and budget impact analysis was also employed. RESULTS The 381 studies were retrieved from systematic searching through databases. After eliminating duplicate and irrelevant studies, 2 studies selected for evaluating the effectiveness. Jadenu was associated with an incremental cost-effectiveness ratio (ICER) of 1470.6 and 2544.7 US$ vs Desferal in first and second scenario respectively. The estimated ICER for Jadenu compared to generic deferoxamine was 2837.0 and 6924.1 US$ for first and second scenario respectively. For all scenarios Jadenu is presumed as cost-effective option based on calculated ICER which was lower than 1 gross domestic product per capita in Iran. Sensitivity analysis showed that different parameters except discount rate and indirect cost did not have impact on results. Based on budget impact analysis the estimated cost for patients using Desferal (based on the market share of brand) was 44,021,478 US$ in 3 years vs 42,452,606 US$ in replacing 33% of brand market share with Jadenu. This replacement corresponded to the cost saving of almost 1,568,872 US$ for the payers in 3 years. The calculated cost of using generic deferoxamine in all patients was 68,948,392 US$. The increase in the cost of using Jadenu for 10% of all patients in this scenario would be 934,427 US$ (1.36%) US$ at the first year. CONCLUSIONS Based on this analysis, film-coated deferasirox appeared to be cost-effective treatment in comparison with Desferal for managing child and adult chronic iron overload in B-thalassemia major patients of Iran.
Modern treatments of haemophilia: review of cost-effectiveness analyses and future directions
BACKGROUND Cost is currently one of the most important aspects in haemophilia care. Factor concentrates absorb more than 90% of healthcare direct costs of haemophilia care, and the debate regarding the high cost of haemophilia treatments and their different use across different countries is increasing. OBJECTIVE The objective of this study was to review cost-effectiveness analyses conducted on treatment options in haemophilia, focusing on their results and their strengths and limitations; to highlight the possible issues associated with economic evaluations of new treatment options. METHODS Electronic searches in PubMed and EMBASE were performed to retrieve papers published between November 2015 and September 2017 to update the previous review of economic evaluations of haemophilia treatments by Drummond et al. Reference lists of included articles and reviews were examined for relevant studies, which were assessed for their quality and their empirical results. RESULTS Twenty-six relevant economic analyses were identified; 15 (57.7%) were conducted in patients with haemophilia with inhibitors while 11 (42.3%) involved patients without inhibitors. There were methodological variations among the included studies, and differences in the treatment schemes make a comparative assessment of interventions for patients with haemophilia difficult. Only immune tolerance induction showed consistent results in its cost-saving profile compared with the treatment with bypassing agents. CONCLUSIONS Economic evaluations of haemophilia treatments are increasing, but the identification of general cost-effectiveness trends is still difficult in these studies. We are now facing a new era in haemophilia management with a soaring need for high-quality economic evaluations, performed through proactive collaboration between clinical experts, budget holders and health economists.
Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption
Journal of Medical Economics. 2016;:1-30
BACKGROUND Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, we compared the first extended-half-life-recombinant factor IX (rFIX) product- recombinant factor IX Fc fusion protein (rFIXFc) - with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis. METHODS We compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection. RESULTS Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference = 0.71; P = 0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means = 42.8-74.5 IU/kg/week [93-161%], P<0.001). CONCLUSION Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.
Assessing options for treating haemophilia with inhibitors
Cost per responder associated with romiplostim and rituximab treatment for adult primary immune thrombocytopenia in France . French
Transfusion Clinique et Biologique. 2014;21((2):):85-93.
PURPOSE OF THE STUDY This analysis compared the response rates and cost per responder associated with romiplostim and rituximab in adult immune thrombocytopenia from the French National Health System payer perspective. METHODS A decision analytic model was developed to estimate the cost per patient and per responder of treating adult immune thrombocytopenia patients with romiplostim versus rituximab over 6 months. A systematic literature review identified phase 3 randomized controlled trials. Published response rates were extracted (response definition: >50x10(9) platelets/liter). Resource utilization was based on French and international treatment guidelines, and clinical expert opinion. Unit costs were derived from literature and French reimbursement lists, and included the costs of routine physician visits, treatment administration, and emergency care. Non-responders incurred bleeding-related event costs. RESULTS The literature review identified a phase 3 randomized controlled trial for romiplostim with a response rate of 83%. Due to a lack of phase 3 randomized controlled trials for rituximab, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. Romiplostim and rituximab were associated with similar treatment costs, with an estimated cost per patient for romiplostim of 17,456 and 17,068 for rituximab. Rituximab resulted in a 30% higher cost per responder (27,308 for rituximab versus 21,031 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related hospitalization costs compared to rituximab. CONCLUSIONS Due to its high efficacy leading to lower bleeding-related costs, romiplostim represents an efficient use of resources for adult immune thrombocytopenia patients in the French healthcare system. Copyright 2014 Elsevier Masson SAS. All rights reserved.
What is the clinical effectiveness and cost- effectiveness of erythropoietin-stimulating agents for the treatment of patients with cancer-treatment induced anaemia? Insights from cumulative meta-analyses (CMA) and lessons for cost-effectiveness analyses
Value in Health. 2014;17((7)):A617.
A cost-effectiveness study of intravenous immunoglobulin in childhood idiopathic thrombocytopenia purpura patients with life-threatening bleeding
BACKGROUND Although the international guideline recommends intravenous immunoglobulin (IVIG) as the first-line treatment for childhood idiopathic thrombocytopenia purpura (ITP) with life-threatening bleeding, ITP patients may not be able to access IVIG because of the limitation in health benefit packages especially in developing countries. There remains an important policy question as to whether IVIG used as a first-line treatment is worth the money spent. Thus, the objective of this study was to perform a cost-effectiveness analysis of adding IVIG to the standard treatment of platelet transfusion and corticosteroids, for the treatment of childhood ITP with life-threatening bleeding in the context of Thailand. METHODS A cost-effectiveness analysis using a hybrid model consisting of a decision tree and Markov models was conducted with a societal perspective. The effectiveness and utility parameters were determined by systematic reviews, while costs and mortality parameters were determined using a retrospective electronic hospital database analysis. All costs were presented in 2012 US$. The discount rate of 3 % was applied for both costs and outcomes. One-way and probabilistic sensitivity analyses were also performed. RESULTS The incremental cost-effectiveness ratio (ICER) was $3,172 per quality-adjusted life-year gained ($/QALY) for the addition of IVIG versus standard treatment alone. The probability of response to corticosteroids was the most influential parameter on ICER. According to the willingness-to-pay of Thailand, of approximately $3,861/QALY, the probability of IVIG being cost effective was 33 %. CONCLUSIONS The addition of IVIG to standard treatment in the treatment of childhood ITP with life-threatening bleeding is possibly a cost-effective intervention in Thailand. However, our findings were highly sensitive. Policy makers may consider our findings as part of the information for their decision making.
Hemoglobin level at initiation of darbepoetin alfa: impact on need for transfusion and associated costs in chemotherapy-induced anemia treatment in Europe
Supportive Care in Cancer. 2013;21((2):):485-93.
PURPOSE Erythropoiesis-stimulating agents can reduce red blood cell transfusion rates in patients developing anemia while receiving chemotherapy. We investigated potential cost savings from reduced transfusion rates in patients starting darbepoetin alfa (DA) at higher versus lower hemoglobin (Hb) levels. METHODS Two systematic literature reviews were performed: transfusion outcomes in patients receiving DA stratified by baseline Hb level and costs of transfusion in Europe. Potential cost savings were calculated by multiplying the difference in transfusion rates between Hb levels by the midpoint of transfusion costs. RESULTS Despite differences in baseline characteristics, treatment duration and analysis technique, the clinical studies (n=8) showed that fewer transfusions were required when DA was initiated at higher versus lower Hb levels. The economic studies (n=9) showed that 1unit of transfusion ranged from 130 to 537 (2010-adjusted values). Cost savings from initiating DA at higher versus lower Hb levels were 503-2,226 (2units transfused) and 880-3,895 (3.5units) per ten patients. CONCLUSIONS Transfusion incidence increases with DA initiation at lower Hb levels. Potential cost savings depend on the number of units transfused and cost items included. DA initiation according to guidelines can reduce transfusions and potentially reduce transfusion-associated costs. Journal Article.
Economic assessment of recombinant factor IX in prophylaxis for hemophilia B in young patients in Mexico
Value in Health. 2013;16((3):):A118.. Abstract No. PSY42.