Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis

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.

Pre-procedural use of thrombopoietin-receptor agonists in cirrhosis and severe thrombocytopenia: A systematic review and meta-analysis

“…Regarding cost of these agents, the NICE concluded that based on a recent cost analysis by the pharmaceutical company manufacturing Lusutrombopag, that it was "…highly likely that lusutrombopag would reflect a good use of scarce NHS resources" [21] . This contrasts the recent National Institute for Health Research abstract which concluded that Avatrombopag and Lusutrombopag were not cost effective given their lack of long-term benefit and increase in drug cost [30] .…”

Thrombocytopenia and Hemostatic Changes in Acute and Chronic Liver Disease: Pathophysiology, Clinical and Laboratory Features, and Management

“…Several studies have assessed the clinical effectiveness in relation to the estimated cost-effectiveness of avatrombopag, lusutrombopag, and platelet transfusions. Some results of these analyses are equivocal or conflicting [ 91 , 92 , 93 , 94 ]. For example, Mladsi et al, reported that avatrombopag reduced the need for platelet transfusions and thus produced cost-savings compared with platelet transfusion (80% fewer prophylactic platelet transfusions, USD 4250 lower costs) or lusutrombopag (42% fewer platelet transfusions, USD 5820 lower costs) [ 91 , 92 ].…”

“…For example, Mladsi et al, reported that avatrombopag reduced the need for platelet transfusions and thus produced cost-savings compared with platelet transfusion (80% fewer prophylactic platelet transfusions, USD 4250 lower costs) or lusutrombopag (42% fewer platelet transfusions, USD 5820 lower costs) [ 91 , 92 ]. Others concluded from their cost-effectiveness analysis that avatrombopag and lusutrombopag are more expensive than no TPO receptor agonist over lifetime, as savings from avoiding platelet transfusions are exceeded by the drug cost and appear to be without long-term health benefits [ 93 ]. However, such a contention disregards that platelet transfusions are inappropriate as a sustained management option in patients with chronic liver disease.…”

A cost‐effectiveness analysis of lusutrombopag for thrombocytopenia in patients with chronic liver disease in Japan

“…However, as our model did not account for these variables, the results of our analysis are conservative and do not include these additional costs. Recently, Armstrong et al reported a systematic review and CEA of thrombopoietin receptor agonists avatrombopag ((Doptelet®; Dova Pharmaceuticals, Durham, NC, USA) and LUSU for thrombocytopenia in people with CLD needing an elective procedure 27 . Although it is not appropriate to compare our result with them due to differences in the medical environment and the model structure used in the analysis, they concluded that avatrombopag and LUSU were superior to no thrombopoietin receptor agonist in avoiding both PT and rescue therapy, but they were not cost‐effective given the lack of benefit and increase in cost under the UK setting.…”