Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura : A Single Technology Appraisal

Evidence Review Group (ERG) final report for the National Institute for Health and Clinical ExcellencePublisher PD

A Retrospective Observational Single-Centre Study on the Burden of Immune Thrombocytopenia (ITP)

Background: German data on economic consequences of immune thrombocytopenia (ITP) are limited. Patients and Methods: A retrospective, observational study based on chart review of adult patients with a confirmed diagnosis of ITP was conducted at a German university hospital. Costs are presented from the hospital perspective. Results: Of 50 eligible patients, 45 could be classified by disease duration: 19 patients = 3 to = 12 months (38%, chronic ITP). Complications included 85 bleeding events in 43 patients, including 3 intracranial haemorrhages. Documented were 955 outpatient visits in 43 patients (86%) and 92 inpatient hospital admissions in 45 patients (90%). Of the 46 patients (92%) treated, all received corticosteroids, 25 (50%) intravenous immunoglobulin, and 7 (14%) further therapies. 12 patients (24%) underwent splenectomy. Average total direct medical costs (mean (standard deviation)) were (sic) 17,091 ((sic) 18,859) per patient, (sic) 12,749 ((sic) 11,663) in 17 newly diagnosed ITP patients with a 0.88-month (0.65 months) average disease duration, and (sic) 29,868 ((sic) 29,397) in 13 chronic ITP patients with a 33.5-month (16.8 months) average disease duration. Inpatient stays were the main cost drivers. Conclusion: These data concerning current healthcare provision for ITP patients in Germany indicate considerable resource consumption and the need for more effective treatment options in individual patients

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians

Cost-Effectiveness of Eltrombopag versus Romiplostim for the Treatment of Chronic Immune Thrombocytopenia in England and Wales

Objective: To evaluate the cost-effectiveness of eltrombopag compared with romiplostim as a treatment for chronic immune thrombocytopenia (cITP) in patients who are splenectomized or ineligible for splenectomy and are treatment refractory in England and Wales. Methods: A Markov cohort model in which patients were administered a sequence of treatments was used to predict long-term outcomes associated with each treatment. The model was informed by data from the eltrombopag clinical trial program and the available literature. The analysis was conducted from the perspective of the United Kingdom National Health Service, and a lifetime time horizon was used. Deterministic and probabilistic sensitivity analyses were performed. Results: Eltrombopag dominated romiplostim (i.e., eltrombopag was as effective as but less costly than romiplostim) in both splenectomized and non-splenectomized patients, assuming a class effect for the two treatments. Eltrombopag also dominated romiplostim in the majority of deterministic sensitivity analyses with the exception of when indirect efficacy estimates were incorporated into the model. In this analysis, eltrombopag no longer dominated romiplostim but remained cost-effective versus romiplostim at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year (QALY). Probabilistic sensitivity analysis demonstrated that there was a 99% and 92% chance of eltrombopag being cost-effective at a cost-effectiveness threshold of £20,000/QALY in splenectomized and non-splenectomized patients, respectively. Conclusions: Results of this study demonstrate that eltrombopag is cost-effective when compared to romiplostim as a treatment for cITP, representing good value for the United Kingdom National Health Service

Eltrombopag: an update on the novel, non-peptide thrombopoietin receptor agonist for the treatment of immune thrombocytopenia

Immune thrombocytopenia (ITP) is characterised by a transient or persistent decrease in platelets accompanied by an increased risk of bleeding, which can have a significant negative impact on patients' health-related quality of life. The condition has long been associated with an increased rate of immune-mediated platelet destruction, and traditional treatments have targeted the reduction in platelet destruction; however, some interventional drugs are limited by transient efficacy and side effects. Recent advances in our understanding of ITP pathogenesis have highlighted the role of impaired platelet production, which has led to the advent of a new generation of thrombopoietin (TPO)-receptor agonist therapies, including eltrombopag and romiplostim. The oral, non-peptide TPO-receptor agonist eltrombopag has shown considerable promise in both preclinical and clinical trials. Eltrombopag has a unique mechanism of action and binds to a transmembrane region of the TPO receptor that is distant from the TPO binding site. As such, eltrombopag may confer synergistic effects with endogenous TPO rather than competing for binding. Eltrombopag also induces activation of the TPO receptor and downstream signalling in a distinct manner to TPO and does not have a significant impact on platelet function. Clinical evidence demonstrates that eltrombopag produces a rapid and sustainable increase in platelet counts that significantly reduces bleeding and is well tolerated in patients with ITP. Eltrombopag therefore represents an important addition to the therapeutic armamentarium for IT

A 19 Year Old Male With HIV Presents With Diffuse Lymphadenopathy

Background In 1872, Moritz Kaposi first described an idiopathic multiple pigmented sarcoma of the skin;\u27\u27 now identified as Kaposi\u27s sarcoma (KS).\u27 While multiple forms ofKSexist, over9S% of the cases diagnosed in the US since 1981 are of the AIDS associated variety.2 Kaposi originally described KS as skin lesions that can progress to visceral involvement. However, in a small number of cases, KS can appear in the viscera without skin involvement. These alternate presentations of KS are difficult to diagnose; therefore, it is critical to recognize them when considering differential diagnoses, particularly in patients with HIV. Case Presentation An 18-year-old African American male with a history ofHIV presented with progressive worsening of diffuse and painful lymphadenopathy fore five weeks prior to admission. The patient was diagnosed with HIV in 2010 and due to insurance issues, was never treated with highly active antiretroviral therapy (HAART). His last CD4 count (approximately two weeks prior to admission) was 411 and he had no history of opportunistic infections. He first noticed swelling in his neck, under his armpits and in his groin five weeks prior, which had become progressively more painful. The patient denied fevers, chills or weight loss, but did report significant night sweats and episodes ofhemoptysis with dots. He denied shortness ofbreath or chest pain. He also denied recent travel, history of incarceration, homelessness or exposure to active tuberculosis infection

Use of Thrombopoietin Receptor Agonists in Childhood Immune Thrombocytopenia

Most children with immune thrombocytopenia (ITP) will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long-term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA) have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data are emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long-term safety issues that need to be considered when using these agents