Characterization and treatment of immune thrombocytopenia in Europe: a qualitative observational study.

BACKGROUND: Immune thrombocytopenia (ITP) is a rare disease, characterized by increased platelet destruction/suboptimal platelet production, leading to thrombocytopenia and risk of severe bleeding events. METHODS: Interviews with 23 physicians and 12 payors, a survey with 113 physicians and validation using published data were used to define the current treatment paradigm and healthcare resource utilization and to determine the costs associated with managing acute bleeds in six European countries (Germany, Spain, France, Italy, Netherlands, UK). The study estimated a prevalence of 9 to 10 per 100,000 adults in 2020 across all six countries (disease severity split: 34% mild, 32% moderate, 33% severe (due to rounding up some values might not sum up to 100%). RESULTS: Physician feedback showed that most patients with ITP (60%) received first-line treatment or were monitored by their physician; ∼75% of patients relapsed within 3-4 months. Thrombopoietin-receptor agonists (TPO-RAs) and rituximab were used to achieve disease stabilization in patients who relapse; patients could switch to an alternative TPO-RA to control symptoms, manage side-effects or improve adherence. The costs of rescue therapies and hospital services (e.g. surgery and admissions) accounted for the majority of healthcare resources to manage bleeding events. CONCLUSION: Physicians would welcome earlier use of TPO-RAs to help maintain long-term control of ITP bleeds and potentially reduce both hospitalization and therapy costs.

The Cost-effectiveness of Eltrombopag for the Treatment of Immune Thrombocytopenia in the United States.

PURPOSE: Eltrombopag was evaluated as a second-line treatment for adult chronic immune thrombocytopenia (ITP) in the 2006 Phase III RAISE (Eltrombopag for Management of Chronic Immune Thrombocytopenia) randomized, placebo-controlled trial. More than 80% of patients reached satisfactory platelet counts within 2 weeks. However, the economic value of eltrombopag as a second-line treatment for ITP remains to be formally assessed. This study aimed to estimate the cost-effectiveness of treating ITP with a comparable thrombopoietin receptor agonist (eltrombopag vs romiplostim). METHODS: A Markov model was implemented over a lifetime time horizon to estimate the benefits and costs of each treatment. The model featured 3 health states based on current guidelines: (1) on treatment; (2) treatment failure/discontinuation; and (3) mortality. In line with therapeutic goals in ITP, model patients could experience 3 events: no bleeding, mild/moderate bleeding, or severe bleeding. Data on eltrombopag use were obtained from an open-label extension of previous Phase II/III trials, including RAISE. Romiplostim data were obtained from Phase III trials and an extension study. Lifetime overall survival was extrapolated by using treatment-specific mortality rates derived from severe bleeding and natural mortality rates. The costs of drugs, routine care, bleeding episodes, adverse events, and mortality were represented in the model. FINDINGS: Eltrombopag-treated patients gained 17.58 life years and 14.68 quality-adjusted life years, whereas romiplostim-treated patients gained 17.52 life years and 14.67 quality-adjusted life years. The total lifetime cost of eltrombopag treatment was estimated at $1.58 million versus $2.13 million for romiplostim. Sensitivity analyses supported base case findings. Deterministic sensitivity analysis predicted the greatest sensitivity to the rates of severe bleeding, discontinuation, and natural mortality. Probabilistic sensitivity analysis showed that eltrombopag would be an efficient use of resources at a $50,000 threshold in 52.8% of cases. In all probabilistic iterations, the total cost of eltrombopag treatment was lower than with romiplostim, primarily because of lower drug costs. IMPLICATIONS: Clinical data were applied in an economic analysis, and eltrombopag exhibited economic dominance compared with romiplostim, driven largely by the reduced costs of primary therapy. This model was limited by a lack of specific patient-level data and robust data on the duration of secondary therapy, as well as by the fact that utilization values are likely conservative estimates for routine care use.

Cost per response analysis of strategies for chronic immune thrombocytopenia.

OBJECTIVES: This analysis estimated the cost per response and the incremental cost per additional responder of romplostim, eltrombopag, and the "watch-and-rescue" (monitoring until rescue therapies are required) strategy in adults with chronic immune thrombocytopenia (ITP). STUDY DESIGN: The decision tree is designed to estimate the total cost per response for romiplostim, eltrombopag, and watch and rescue over a 24-week time horizon; cost-effectiveness was evaluated in terms of incremental cost per additional responder. METHODS: Model inputs including response rates, bleeding-related episode (BRE) rates, and costs were estimated from registrational trial data, an independent Bayesian indirect comparison, database analyses, and peer-reviewed publications. Costs were applied to the proportions of patients with treatment response and nonresponse (based on platelet count). The total cost per response and the incremental cost per additional responder for each treatment were calculated. Sensitivity analyses and alternative analyses were performed. RESULTS: With higher total costs and greater treatment efficacy, romiplostim and eltrombopag had a lower 24-week cost per response and a lower average number of BREs than watch and rescue. Eltrombopag was weakly dominated by romiplostim. The incremental cost-effectiveness ratio of romiplostim versus watch and rescue was $46,000 per additional responder. The model results are most sensitive to response rates of romiplostim and watch and rescue and the BRE rate for splenectomized nonresponders. Alternative analyses results were similar to the base case. CONCLUSIONS: In adults with chronic ITP, romiplostim represents an efficient way to achieve response, with lower costs per response than eltrombopag; both romiplostim and eltrombopag had lower costs per response than watch and rescue.

[Cost-per-responder analysis comparing romiplostim to rituximab in the treatment of adult primary immune thrombocytopenia in Spain]. / Coste por paciente con respuesta a romiplostim y rituximab en el tratamiento de la trombocitopenia inmune primaria en España.

BACKGROUND AND OBJECTIVE: Romiplostim, a thrombopoietin-receptor agonist, is approved for second-line use in idiopathic thrombocytopenic purpura (ITP) patients where surgery is contraindicated. Anti-CD20 rituximab, an immunosuppressant, is currently used off-label. This analysis compared the cost per responder for romiplostim versus rituximab in Spain. MATERIALS AND METHOD: A decision analytic model was constructed to estimate the 6-month cost per responding patient (achieving a platelet count≥50×10(9)/l) according to the most robust published data. A systematic literature review was performed to extract response rates from phase 3 randomized controlled trials. Romiplostim patients received weekly injections; rituximab patients received 4 weekly intravenous infusions. Medical resource costs were obtained from Spanish reimbursement lists. Treatment non-responders incurred bleeding-related event (BRE) management costs as reported in clinical trials. Medical resource utilization and clinical practice were based on Spanish treatment guidelines and validated by local clinical experts. RESULTS: The literature review identified phase 3 romiplostim trials with a response rate of 83%. Due to a lack of phase 3 controlled rituximab trials, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. The mean cost per patient for romiplostim was €16,289 and €13,459 for rituximab. Rituximab resulted in a 10% higher cost per responder (€21,535 versus €19,625 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related costs compared to rituximab. CONCLUSIONS: Due to its high level of efficacy leading to lower BRE costs, romiplostim represents an efficient use of resources for adult ITP patients in the Spanish Healthcare System.

[Cost per responder associated with romiplostim and rituximab treatment for adult primary immune thrombocytopenia in France]. / Coût par patient répondeur associé au traitement du purpura thrombopénique immunologique primaire par romiplostim et rituximab chez l'adulte en France.

PURPOSE OF THE STUDY: This analysis compared the response rates and cost per responder associated with romiplostim and rituximab in adult immune thrombocytopenia from the French National Health System payer perspective. METHODS: A decision analytic model was developed to estimate the cost per patient and per responder of treating adult immune thrombocytopenia patients with romiplostim versus rituximab over 6 months. A systematic literature review identified phase 3 randomized controlled trials. Published response rates were extracted (response definition: ≥50×10(9) platelets/liter). Resource utilization was based on French and international treatment guidelines, and clinical expert opinion. Unit costs were derived from literature and French reimbursement lists, and included the costs of routine physician visits, treatment administration, and emergency care. Non-responders incurred bleeding-related event costs. RESULTS: The literature review identified a phase 3 randomized controlled trial for romiplostim with a response rate of 83%. Due to a lack of phase 3 randomized controlled trials for rituximab, a systematic review of studies was selected as the best source, reporting a response rate of 62.5%. Romiplostim and rituximab were associated with similar treatment costs, with an estimated cost per patient for romiplostim of €17,456 and €17,068 for rituximab. Rituximab resulted in a 30% higher cost per responder (€27,308 for rituximab versus €21,031 for romiplostim). Romiplostim use reduced drug administration, intravenous immunoglobulin, and bleeding-related hospitalization costs compared to rituximab. CONCLUSIONS: Due to its high efficacy leading to lower bleeding-related costs, romiplostim represents an efficient use of resources for adult immune thrombocytopenia patients in the French healthcare system.

[Economic evaluation of Thrombopoietin Receptor Agonists in the treatment of chronic primary immune thrombocytopenia]. / Evaluación económica del tratamiento de la trombocitopenia inmune primaria crónica refractaria con agonistas del receptor de la trombopoyetina.

PURPOSE: To develop a tool to assist the decision-making for selection of Thrombopoyetin Receptor Agonists of adult patients with chronic immune primary thrombocytopenia (PTI). METHODS: Stochastic cost-effectiveness analysis with a 6-Health- States Markov model: stable, bleeding type 2, 3 or 4, post-type 4 bleeding and death. Each simulation analyzes a randomly generated scenario that describes patients characteristics, results measured in quality adjusted life years (QALYs) and costs (in ?2011). Distributions were obtained from the Spanish data of the European health survey of 2009, the INE estimate of population for 2011 and the 6-months clinical studies for Eltrombopag and Romiplostim. Utility values were obtained from the literature and the costs from Spanish official rates lists. A set of 10.000 random scenarios were generated and the patients evolution of each scenario was simulated during a time horizon of five years (in 2-weeks cycles). National Health System Perspective was used and the annual discount rate was set at 3%. RESULTS: Eltrombopag showed more effectiveness in 9.983 scenarios and there was no difference in 17. In 7.048 scenarios the alternative Eltombopag was dominant. It was cost-effective in another 19 (threshold 30,000 ??/AVAC). CONCLUSIONS: Eltrombopag was the most cost-effective alternative in 70,67% of the simulated scenarios and its use could produce lower costs to the NHS.

Objetivo: Desarrollar una herramienta de apoyo a la decisión en la selección de agonistas del receptor de trombopoyetina en el tratamiento de pacientes adultos con trombocitopenia inmune primaria crónica (PTI) refractaria. Métodos: Análisis coste-efectividad estocástico con un modelo de Markov de seis estados: estable, sangrado tipo 2, 3 ó 4, post-sangrado 4 y muerte. Cada simulación analiza un escenario aleatoriamente generado que describe las características del paciente, los resultados medidos en años de vida ajustados a calidad (AVACs) y los costes (en ?2011). Se obtuvieron distribuciones a partir de los datos para España de la Encuesta Europea de Salud de 2009, de la estimación de población para 2011 del INE, de los estudios a 6 meses de Eltrombopag y Romiplostim, de las utilidades obtenidas de la bibliografía y de las tarifas oficiales en España para procesos y actividad. Se generaron 10.000 escenarios aleatorios y se simuló la evolución de los pacientes de cada escenario durante un horizonte temporal de cinco años (ciclos de dos semanas). Perspectiva del Sistema Nacional de Salud (SNS). Tasa de descuento anual del 3% para costes y efectos. Resultados: En 9.983 escenarios Eltrombopag mostró mayor efectividad y en 17 no hubo diferencias. Eltombopag fue la alternativa dominante en 7.048 escenarios y la más coste efectiva en otros 19 (umbral 30.000 ?/AVAC). Conclusiones: Eltrombopag es la alternativa más coste-efectiva en el 70,67% de los escenarios simulados, por lo que su uso podría producir menores costes al SNS.

An analysis of outcomes and treatment costs for children undergoing splenectomy for chronic immune thrombocytopenia purpura.

PURPOSE: Indications and timing for splenectomy in pediatric chronic immune thrombocytopenic purpura (cITP) are controversial because of high spontaneous remission rates and concern for overwhelming postsplenectomy infection. The objective of this study was to assess the risks, costs, and benefits of medical and surgical intervention for children with cITP. METHODS: After receiving institutional review board approval, medical records for all children with cITP who underwent splenectomy from 2002 through 2009 were retrospectively reviewed (n = 22). Preoperative and postoperative data were collected. Medical and surgical costs were calculated based on pharmacy charges per dose and hospital charges, respectively. RESULTS: The median age at diagnosis was 11 years (range, 3-16 years). Medical management included steroids (n = 21), intravenous gamma globulin (n = 19), anti-D antibody (n = 19), or a combination of these therapies (n = 22). Nineteen patients (86%) reported side effects from medical therapy. Median age at splenectomy was 13 years (range, 6-18 years), and time to surgery was 23 months from diagnosis (range, 6-104 months). Splenectomy increased platelet counts in all children from a median of 25,500 to 380,000 postoperatively (P < .0001). One child experienced overwhelming postsplenectomy infection after a dog bite (n = 1). At the last follow-up (15 months; range, 1-79 months), 19 patients (86%) were asymptomatic with platelet counts greater than 50,000. Of the 3 children with persistent thrombocytopenia, 2 were diagnosed with secondary cITP. Median cost of splenectomy was significantly less than the cost of medical therapy ($20,803 vs $146,284; P < .0002). CONCLUSION: Earlier surgical consultation for children with cITP may be justified given the high success rate and low morbidity, particularly given the significant complication rate and cost of continued medical treatment.

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 months (38%, newly diagnosed ITP), 12 patients ≥ 3 to < 12 months (24%, persistent ITP), 19 patients ≥ 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 17,091 (18,859) per patient, 12,749 (11,663) in 17 newly diagnosed ITP patients with a 0.88-month (0.65 months) average disease duration, and 29,868 (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.

The burden of immune thrombocytopenia in adults: evaluation of the thrombopoietin receptor agonist romiplostim.

BACKGROUND: Immune thrombocytopenia (ITP) is a chronic, immune-mediated disease characterized by a transient or long-lasting decrease in platelet counts. ITP is associated with numerous serious clinical consequences. Discussed here are clinical aspects of ITP, the humanistic and economic burden of ITP, and current treatment options with a focus on romiplostim, a thrombopoietin (TPO) receptor agonist. The aim of this review is to provide decision-makers with the background information necessary to evaluate the value of romiplostim. SCOPE: PubMed was searched for relevant, English-language papers published from January 2006 through November 2011 relating to the epidemiology and treatment options of chronic ITP, and, focusing on the TPO mimetic romiplostim, patient-reported outcomes (PRO) and economic burden. Recent select conference abstracts were also reviewed. FINDINGS: The initial clinical management of ITP (e.g., corticosteroids, immunoglobulins) is often associated with adverse events and recommended for short-term use only. Splenectomy, a potentially curative second-line treatment, is associated with increased risks of bleeding and infection, and patients often require additional long-term drug intervention. ITP and its sequelae are associated with a substantial burden on patients' health-related quality-of-life (HRQoL) and increased medical costs. Use of TPO receptor agonists in ITP patients may represent a more efficient use of healthcare resources than existing therapies. CONCLUSION: While this literature review is not a systematic review, e.g., it considers only approved therapies and published literature written in English, it provides a comprehensive overview of the clinical, humanistic, and economic factors that should be considered in treating ITP, particularly with new agents such as romiplostim. Among the limited number of safe and effective therapies currently available for chronic ITP, highly effective and well-tolerated medications such as romiplostim may reduce the healthcare resource utilization associated with ITP while improving patients' HRQoL.

Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^9/L and 400 × 10^9/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than £30,000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from £33,561 to £103,500 per QALY (splenectomized) and £39,657 to £150,245 per QALY (non-splenectomized). All costs are presented in £, year 2008 values, as this was the costing year for the manufacturer's model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of £30,000 per QALY gained. Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators.

Analysis of EQ-5D scores from two phase 3 clinical trials of romiplostim in the treatment of immune thrombocytopenia (ITP).

OBJECTIVE: Utility-based measures of quality of life are recommended by some decision makers in health care. No studies have addressed changes in utility in patients with chronic idiopathic thrombocytopenia (ITP). This study sought to assess the health utilities of patients with chronic ITP and to evaluate the association of change in health utility with changes in other variables, including platelet response status and bleeding events. METHODS: We analyzed EQ-5D data from two international, randomized, placebo-controlled, double-blind, 24-week trials that evaluated the efficacy and safety of romiplostim in adult patients with chronic ITP. RESULTS: A total of 125 subjects participated. Mean change, adjusted for age, gender, splenectomy status, and baseline score using multiple linear regression models was greater for romiplostim versus placebo for the EQ-5D index score (0.05 vs. -0.03, P = 0.015) and the VAS score (6.42 vs. 0.48, P = 0.066); similar for durable platelet responders versus nonresponders; and greater for EQ-5D index scores for subjects who did not have a bleeding event during the study (n = 29) compared to subjects who did have a bleeding event (n = 47) (0.06 vs. 0.005; P = 0.066). CONCLUSIONS: Using romiplostim in cases of chronic ITP was associated with improvement in health-related quality of life as measured by the EQ-5D index score. Health utility scores derived using the EQ-5D in this study may be useful for determining quality-adjusted life years (QALYs) in economic evaluations of romiplostim for treatment of chronic ITP.

Measurement of utility values in the UK for health states related to immune thrombocytopenic purpura.

OBJECTIVE: To measure utility values associated with immune (idiopathic) thrombocytopenic purpura (ITP), as perceived by the United Kingdom (UK) general public. RESEARCH DESIGN AND METHODS: A multi-step process, including clinical trial data, literature review, and patient focus group, was used to develop ITP health states valued in a web survey. Six ITP health states were defined based on platelet levels, risk of bleeding and key adverse events/disease complications. Clinical trial data on bleeding and ITP-specific quality of life data were key sources for developing health-state descriptions. 359 respondents, randomly selected from a managed web panel in the UK, completed the web-based Time Trade-Off survey. Wilcoxon signed-rank test was used to compare differences between each pair of health states. RESULTS: Sample characteristics (mean age: 47.9 +/- 16.9 years; 54% female) were comparable to the UK general population. ITP health states were valued as significantly worse than perfect health. Experiencing bleeding episodes was a more important driver than low platelet levels in valuing a health state to be worse. Substantial disutilities were associated with surviving an intracranial haemorrhage. Mean (SD) utility values for each ITP health state are: HS1: platelets >or=50 x 10(9)/L, no outpatient bleed: 0.863 +/- 0.15; HS2: platelets >or=50 x 10(9)/L, outpatient bleed: 0.734 +/- 0.19; HS3: platelets <50 x 10(9)/L, no outpatient bleed: 0.841 +/- 0.19; HS4: platelets <50 x 10(9)/L, outpatient bleed: 0.732 +/- 0.19; HS5: intracranial haemorrhage (2-6 months): 0.038 +/- 0.46; HS6: steroid treatment adverse events: 0.758 +/- 0.20. Potential limitations relate to web user population characteristics and lack of comparative testing of web-based TTO methods. CONCLUSIONS: Results provide evidence that the UK general population associate substantial loss of value living with ITP, suggesting an important role for new ITP treatments. Utility values based on these health states may be useful in future cost-effectiveness studies of existing and/or new ITP treatments.

Romiplostim: a novel thrombopoiesis-stimulating agent.

PURPOSE: The pharmacology, pharmacokinetics, dosage and administration, efficacy, safety, effects on quality of life, and place in therapy of romiplostim are reviewed. SUMMARY: Romiplostim is a second- generation thrombopoietic agent that stimulates the thrombopoietin receptor and platelet production without inducing production of autoantibodies. Romiplostim, a peptibody, bears no structural resemblance to endogenous thrombopoietin, thus minimizing the risk for development of thrombopoietin autoantibodies. Clinical trials have shown that romiplostim increases platelet counts compared with placebo in both splenectomized and non-splenectomized adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Clinical trials with romiplostim are ongoing for patients with myelodysplastic syndrome and those receiving chemotherapy for treatment of malignancies. Romiplostim may confer an increased risk of bone marrow reticulin formation or fibrosis, malignancy, thrombosis, and thrombocytopenia that is more severe than the level present before initiation of romiplostim. While all patients receiving romiplostim in clinical trials experienced at least one adverse event, most were mild to moderate in severity. The most frequent adverse effects were ecchymosis, headache, and petechiae. Romiplostim is initiated at a dosage of 1 microg/kg subcutaneously once weekly and titrated to achieve platelet counts between 50 and 200 x 10(9) platelets/L, with a maximum dose of 10 microg/kg. Romiplostim is only available through the manufacturer's risk-management program. The current wholesale price of romiplostim is $1,062.50 for a single-use vial of 250 microg or $2,125 for a single-use vial of 500 microg. The extrapolated drug cost for weekly dosing for one year is approximately $55,250. CONCLUSION: Romiplostim is a novel thrombopoietic-stimulating agent for use in patients with chronic ITP who have not responded to other therapies.

A cost-utility analysis of treatment for acute childhood idiopathic thrombocytopenic purpura (ITP).

BACKGROUND: The primary objective in the treatment of acute pediatric idiopathic thrombocytopenic purpura (ITP) is to rapidly increase the platelet count. METHODS: We built a decision analytic model to evaluate the cost-utility of four commonly used treatment strategies: intravenous immunoglobulin G (IVIG) 0.8 g/kg, anti-D 75 mcg/kg, methylprednisolone (30 mg/kg for 3 days), and prednisone (4 mg/kg/day for 4 days). In our baseline model, all children were hospitalized upon presentation, and discharged once the platelet count reached > or =20,000. We performed a literature search to estimate time to platelet count > or =20,000 for each strategy, as well as the probability of side effects. We obtained cost data and quality of life measures from institutional and published data sources. RESULTS: Total cost of one-time treatment for a 20 kg child was US dollars 786 with prednisone, US dollars 1,346 with methylprednisolone, US dollars 2,035 with anti-D, and US dollars 2,492 with IVIG. The strategies of IVIG and methylprednisolone were less effective and more expensive than anti-D and prednisone, respectively. Although anti-D caused the most rapid rise in platelet counts, the incremental cost-utility ratio (costs incurred by using anti-D instead of prednisone divided by health benefit of using anti-D instead of prednisone) was US dollars 7,616 per day of severe thrombocytopenia avoided, primarily due to the much higher medication cost of anti-D. Utilizing an outpatient model, the cost difference between anti-D and prednisone was even more striking. CONCLUSIONS: The clinical benefit of anti-D is offset by a substantial cost increase. Although often overlooked in favor of newer agents, a brief course of high-dose prednisone is an inexpensive and effective treatment for acute ITP.

Prospective evaluation of high-cost management of severe chronic ITP in children and adolescents<16 years.

Chronic ITP rarely presents with severe bleeding episodes (SBE). Number and duration of SBE were evaluated in relation to the cost of management. Out of 157 chronic ITP patients attending our institution from 1994 to 2003, 37 patients, <16 years with persistent thrombocytopenia (>6 months), suffering from SBE or platelet count<10x10(9)/L were prospectively randomized to receive either intravenous immunoglobulins (IVIG), anti-D immunoglobulin (anti-D) or high-dose methyl prednisolone (HDMP). Sixty-one patient-years were followed, during which 351 SBE were documented. The high-cost management (IVIG and anti-D) showed insignificantly better platelet recovery, less frequent SBE with shorter duration per patient, higher rate of CR, and less splenectomy in contrast to the steroid groups. The effectiveness of high-cost management compared with methyl prednisolone could not be documented in this study.

Open versus laparoscopic splenectomy for idiopathic thrombocytopenic purpura: clinical and economic analysis.

BACKGROUND: Since 1991, laparoscopic splenectomy (LS) has gained acceptance in the treatment of hematologic disorders, including idiopathic thrombocytopenic purpura (ITP). Several studies suggest that LS provides benefits over open splenectomy (OS). However, study design flaws hinder formal technology assessment. METHODS: We retrospectively reviewed medical and administrative records of patients who underwent splenectomy for ITP between January 1995 and December 2000 to compare clinical and economic outcomes associated with LS and OS. RESULTS: Eighty-six patients were identified; 42 underwent an attempted LS and 44 had OS. Preoperative patient characteristics were similar between groups. Mean operative and anesthesia times for LS and OS were 167 and 201 minutes and 119 and 151 minutes, respectively (P <.001). Overall transfusion and postoperative complication rates were similar between groups. On average, LS patients required 1.2 fewer days of parenteral analgesia and were able to tolerate a general diet 1.7 days earlier. Mean postoperative stay was 2 days lower for LS patients and mean total direct costs did not differ by surgical method (US dollars 8134 vs US dollars 8200). CONCLUSIONS: This observational study shows that LS is safe and offers advantages over OS: less postoperative pain, earlier general diet tolerance, and shorter hospital stay. These benefits are obtained at no significant additional cost.

Laparoscopic splenectomy: reduction of hospital charges.

Laparoscopic splenectomy has become our procedure of choice for the surgical management of immune thrombocytopenic purpura. Hospital charges for this procedure were analyzed for 24 consecutive patients undergoing laparoscopic splenectomy. Total charges have decreased over time and average a $233 decrease per patient treated. The decreased charges are related to decreased operating room charges. Furthermore, charges are shown to be related to the length of postoperative stay. Choice of instrumentation has kept intraoperative charges for disposables stable.