1.
Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis
Armstrong N, Büyükkaramikli N, Penton H, Riemsma R, Wetzelaer P, Huertas Carrera V, Swift S, Drachen T, Raatz H, Ryder S, et al
Health technology assessment (Winchester, England). 2020;24(51):1-220
Abstract
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.
2.
Dose efficiency of erythropoiesis-stimulating agents for the treatment of patients with chemotherapy-induced anemia: a systematic review
Forbes CA, Worthy G, Harker J, Kleijnen J, Kutikova L, Zelek L, Van Belle S
Clinical Therapeutics. 2014;36((4):):594-610.
Abstract
BACKGROUND Erythropoiesis-stimulating agents (ESAs) increase red blood cell production in patients with chemotherapy-induced anemia (CIA). In Europe, short-acting ESAs (epoetin alfa, epoetin beta, epoetin zeta, and epoetin theta) and a long-acting ESA (darbepoetin alfa) are available to treat CIA. OBJECTIVE This systematic review aimed to determine potential dose efficiency associated with the use of different ESAs for the treatment of CIA according to European labeling. METHODS A systematic review of ESA studies with starting doses according to European labeling was conducted according to published methodology. Measures of dose efficiency were defined as mean weekly doses to achieve target hemoglobin level or final dose and dose adjustments (dose increase, decrease, or withheld). Electronic databases and grey literature sources were searched up to July 2012. Data were selected for analysis using an evidence hierarchy and quantitatively analyzed to assess statistical homogeneity. Where pooling of data was not appropriate, a narrative summary with descriptive statistics (medians and ranges) was reported. RESULTS Fifty-five studies met the inclusion criteria. Twenty-five studies considered to represent the highest level of evidence were extracted and included in the analysis. The analysis showed a high degree of statistical heterogeneity, often precluding meta-analysis. The patients included in the analysis were representative of those encountered in clinical practice, and patient characteristics were similar between the short-acting and the darbepoetin alfa groups. Mean weekly doses appeared ~30% lower with darbepoetin alfa versus short-acting ESAs (median, 136.5 mug or 27,300 IU [range, 21,560-38,260 IU] vs 38,230 IU [range, 31,634-42,714 IU], respectively), resulting in a mean weekly dose ratio of 1:280. Darbepoetin alfa patients appeared to need fewer dose increases compared with short-acting ESAs (pooled, 0.75%; I(2) = 21% vs median 26.6% [range, 7.6%-44.6%]) and more dose decreases (median, 74% [range, 57%-75%] vs 22% [range, 2.8%-59%]). A similar percentage of darbepoetin alfa and short-acting ESA patients required a dose to be withheld (20% and 33% [2 studies] vs median 33.2% [range, 12.6%-51.1%]). CONCLUSIONS Statistical heterogeneity between studies was high, although clinically the studies represented medical practice. Without randomized clinical trials directly comparing darbepoetin alfa and short-acting ESAs, these findings are tentative and future research is warranted. This review shows that good-quality, reliable data from head-to-head trials are lacking. The best available evidence comes from prospective ESA-arm data. Mean weekly doses, dose increases, and dose decreases suggest a dose efficiency for darbepoetin alfa compared with short-acting ESAs. Copyright 2014 The Authors. Published by EM Inc USA.. All rights reserved.