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

Nigel Armstrong, Nasuh Büyükkaramikli, Hannah Penton, Rob Riemsma, Pim Wetzelaer, Vanesa Huertas Carrera, Stephanie Swift, Thea Drachen, Heike Raatz, Steve Ryder, Dhwani Shah, Titas Buksnys, Gill Worthy, Steven Duffy, Maiwenn Al, Jos Kleijnen
Record ID 32018000802
Authors' objectives: 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. 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.
Authors' results and conclusions: 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. 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.
Authors' methods: Systematic review and cost-effectiveness analysis. Secondary care. Severe thrombocytopenia (platelet count of < 50,000/μl) in people with chronic liver disease requiring surgery. 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). Risk of platelet transfusion and rescue therapy or risk of rescue therapy only. 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. Model-based cost-effectiveness analysis. 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.
Authors' identified further reserach: A head-to-head trial is warranted.
Project Status: Completed
Year Published: 2020
URL for published report: https://doi.org/10.3310/hta24510
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: England
DOI: 10.3310/hta24510
MeSH Terms
  • Thrombocytopenia
  • End Stage Liver Disease
  • Elective Surgical Procedures
  • Surgical Procedures, Operative
Organisation Name: NIHR Health Technology Assessment programme
Contact Address: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK
Contact Name: journals.library@nihr.ac.uk
Contact Email: journals.library@nihr.ac.uk
Copyright: Queen's Printer and Controller of HMSO
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.