lusutrombopag and End-Stage-Liver-Disease

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. 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.. 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.. 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.. 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.. A head-to-head trial is warranted.. This study is registered as PROSPERO CRD42019125311.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in

Topics: Bayes Theorem; Cinnamates; Clinical Trials as Topic; Cost-Benefit Analysis; End Stage Liver Disease; Humans; Models, Economic; Platelet Transfusion; Quality-Adjusted Life Years; Receptors, Thrombopoietin; Secondary Care; Technology Assessment, Biomedical; Thiazoles; Thiophenes; Thrombocytopenia

Bleeding may interfere with the visual field and create difficulties in performing the intended treatment, especially in operations involving a small working space such as endoscopic spinal surgery. Therefore, it is important to reduce the risk of bleeding before surgery.. A 76-year-old female presented with a history of right anterior thigh pain along the L3 dermatome for 3-years, following a L3 compression fracture. In addition, the patient had developed autoimmune hepatitis at 50 years of age, and the platelet count on laboratory blood collection was 78 × 109/L.. Magnetic resonance (MR) images showed a narrowed foramen at the L3-4 level. L3 nerve block was effective. L3 foraminal-stenosis was suspected.. Micro-endoscopic laminectomy (MEL) for foraminal decompression was planned due to possible L3 nerve root compression. Lusutrombopag, a thrombopoietin (TPO) receptor agonist, was orally administered for 7 days starting 7 days preoperatively to address the risks of bleeding.. The patient successfully underwent MEL without any adverse events or complications.. The results obtained from the use of lusutrombopag suggested that safety measures could be implemented preoperatively, and that lusutrombopag may be a useful supplemental drug for minimally invasive treatment of patients with cirrhosis and thrombocytopenia.

Topics: Aged; Blood Loss, Surgical; Cinnamates; End Stage Liver Disease; Endoscopy; Female; Humans; Lumbar Vertebrae; Spinal Fractures; Thiazoles; Thrombocytopenia

Platelets are produced by hematopoietic stem cells via megakaryocytes in the bone marrow and play a critical role in hemostasis. The aim of this study was to develop a new platelet model based on the thrombopoiesis and platelet life-cycle by a quantitative systems pharmacology modeling approach, which could describe changes in platelet count profiles in platelet-related diseases and drug intervention. The proposed platelet model consists of 44 components. The model was applied to thrombopoiesis of a thrombopoietin receptor agonist, lusutrombopag. It could well describe the observed platelet count profiles after administration of lusutrombopag for both healthy subjects and patients with chronic liver disease and thrombocytopenia. This model should be useful for understanding the disease progression of platelet-related conditions, such as thrombocytopenia and for predicting platelet count profiles in various disease situations related to platelets and drug administration in drug development.

Topics: Blood Platelets; Cinnamates; Computer Simulation; End Stage Liver Disease; Humans; Receptors, Thrombopoietin; Thiazoles; Thrombopoiesis