Background Romiplostim, a thrombopoietin receptor agonist (TPOra), is a second-line medical treatment option for adults with chronic immune thrombocytopenia (ITP). Clinical trials have shown that romiplostim increases platelet counts, while reducing the risk of bleeding and, in turn, the need for costly rescue medications. Aims The objective of this study was to assess the cost effectiveness of romiplostim in the treatment of adult ITP in Ireland, in comparison with eltrombopag and the medical standard of care (SoC). Methods A lifetime treatment-sequence cost-utility Markov model with embedded decision tree was developed from an Irish healthcare perspective to compare romiplostim with eltrombopag and SoC. The model was driven by platelet response (platelet count ≥50 × 10 9 /L), which determined effectiveness and progression along the treatment pathway, need for rescue therapy (e.g. intravenous immunoglobulin [IVIg] and steroids) and risk of bleeding. Probability of response, mean treatment duration, average time to initial response and utilities were derived from clinical trials and other published evidence. Treatment sequences and healthcare utilization practice were validated by Irish clinical experts. Costs were assessed in € for 2011 and included drug acquisition costs and costs associated with monitoring patients and management of bleeding, as available from published Irish reimbursement lists and other relevant sources. Deterministic and probabilistic sensitivity analyses were conducted. Results Romiplostim treatment resulted in an average of 20.2 fewer administrations of rescue medication (IVIg or intravenous steroids) over a patient lifetime than eltrombopag, and 29.3 fewer rescue medication administrations than SoC. Romiplostim was dominant, with cost savings of €13,258 and €22,673 and gains of 0.76 and 1.17 quality-adjusted life-years (QALYs), compared with eltrombopag and SoC, respectively. Romiplostim remained cost effective throughout a variety of potential scenarios, including short-term TPOra treatment duration (1 year). One-way sensitivity analysis showed that the model was most sensitive to variation in the cost of IVIg and use of romiplostim and IVIg. Probabilistic sensitivity analysis showed that romiplostim was likely to be cost effective in over 90 % of cases compared with eltrombopag, and 96 % compared with SoC at a willingness-to-pay threshold of €30,000 per QALY. Conclusions Use of romiplostim in the ITP treatment pathway, compared with eltrombopag or SoC, is likely to be cost effective in Ireland. Romiplostim improves clinical outcomes by increasing platelet counts, reducing bleeding events and the use of IVIg and steroids, resulting in both cost savings and additional QALYs when compared with current treatment practices.

Abstract Objective: In clinical studies of patients with severe thrombocytopenia, rescue treatments are used to prevent or stop bleeding. Estimating risk reductions of bleeding for clinical study medications can be challenging. This study evaluated a new and possibly more accurate way of assessing the effects of a treatment intervention on bleeding-related outcomes. We developed a composite endpoint, termed bleeding-related episodes (BRE). Research design and methods: BREs were assessed in a post-hoc analysis of patients with chronic immune thrombocytopenia (ITP) who participated in two romiplostim, phase 3, placebo-controlled studies. Patients received romiplostim or placebo once weekly for 24 weeks. A BRE was defined as an actual bleeding event and/or the use of rescue medication. In total, 125 patients (41 placebo, 84 romiplostim) with platelet counts <30 K were enrolled. Clinical trial registration: NCT00102323/NCT00102336. Results: The rate of all BREs across all studies was reduced by 56% in patients receiving romiplostim compared with placebo. The rate of BREs using immunoglobulin (IVIg or anti-D Ig) was reduced by 89% in patients receiving romiplostim compared with placebo. BREs were more frequent in both groups at platelet counts <50 × 109/L. Results were similar between splenectomized and nonsplenectomized patients. We believe that prior to the development of this tool, bleeding events were underdiagnosed. The BRE tool allowed the identification of multiple interventions within bleeding episodes, which may have required separate interventions and were therefore considered to be additional BREs. Conclusions: In this study, the composite endpoint of a bleeding event and the use of rescue medication within close proximity of the bleeding event appears to be feasible and informative. The BRE tool allows for more precise understanding of the effect of rescue therapies in ITP and has broader applications to future clinical trials where assessment of bleeding risk can be complicated or masked by rescue interventions. Limitations: This was a post hoc analysis. The assignment of platelet counts to a BRE was based on the platelet count on the first day of a BRE, which may not reflect the platelet count during the entire episode, and the assignment of platelet counts was based on the estimation required for events that occurred between weekly measurements.

Background Childhood ITP can have a negative impact on the child and his/her family even though it is typically a benign disorder with low risk of serious bleeding. In adults and now children, romiplostim increases the platelet count without significant adverse effects. In this study, the impact of romiplostim treatment on the HRQoL of children with chronic ITP was assessed using the Kid's ITP Tools (KIT).

Abstract 4640 OBJECTIVES: To compare the drug costs relative to response of two thrombopoietin receptor agonists, romiplostim and eltrombopag, to Watch & Rescue for the treatment of chronic immune thrombocytopenia (ITP), from a health plan perspective. ITP, a diagnosis of exclusion, is characterized by low platelet counts and, depending on platelet count level, increased risk of bleeding (Rodeghiero F, et al. Blood. 2009:113(11):2386–2393). METHODS: An Excel® model compared 2011 US drug costs (wholesale acquisition cost) to the overall patient response rates (four or more weekly platelet counts of ≥50 × 109/L during the study from week 2 to 25) observed in individual 6-month placebo-controlled trials for romiplostim, eltrombopag, and placebo (or Watch & Rescue) (http://www.nice.org.uk/nicemedia/live/12025/50715/50715.pdf). These trials studied patients with median baseline platelet counts of 16 × 109/L (in both the romiplostim and eltrombopag trials) with 51% of the eltrombopag and 64% of the romiplostim patients receiving ≥3 previous treatments prior to joining each respective trial (Kuter, D, et al. Lancet. 2008:371:395–403; Cheng G, et al. Lancet. 2011:377:393–402; Bussel, J, et al. Lancet. 2009:373:641–648). The model considers a 55 mg daily dose of eltrombopag, and an average dose (including wastage) derived from a trial-based simulation for the US of 286 mcg per weekly administration of romiplostim. It assumes that 30% of US patients are splenectomized. The model considers a 1 g/kg overall dose of IVIg per rescue event at an average romiplostim trial-based weighted average (by splenectomy status) rate of 2.29 administrations per 6-month period (Weitz, I, et al. Curr Med Res Opin. 2012:28(5):789–796). RESULTS: For romiplostim patients, the expected cost of treating a patient with romiplostim over a 6-month period (trial period) is $34,655, with an overall response rate of 83%, or a cost per patient with an overall response of $41,753 ($34,655÷83%). The expected 6-month cost of treating the same patient with eltrombopag is $28,516, for an overall response rate of 57%, or a cost per patient with an overall response of $50,028 ($28,516÷57%). Comparatively, the expected 6-month cost of treating the same patient with Watch & Rescue is $11,681, with an overall response rate of 9%, or a cost per patient with an overall response of $129,789 ($11,681÷9%). Patients treated with thrombopoietin receptor agonists experience a 48 to 74% higher overall response rates than patients treated with Watch & Rescue, at a 153 to 196% reduction in resources to achieve the response. Sensitivity analyses were performed on key variables; a ±50% change in the average 6-month cost of IVIg (from either a decrease in cost or a decrease in the average number of administrations) resulted in ±50% change in the Watch & Rescue cost per response ($64,894 to $194,683). A decrease of 25% to the response rates for romiplostim and eltrombopag individually resulted in a 33% increase in the overall cost per patient with an overall response to $55,670 for romiplostim and $66,704 for eltrombopag. CONCLUSIONS: In chronic adult ITP, the use of thrombopoietin receptor agonists represents an efficient use of healthcare resources, with better health outcomes at a significantly lower cost per treatment success than treatment with Watch & Rescue. Disclosures: Northridge: Amgen Inc.: Consultancy, Research Funding. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

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.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and insufficient platelet production. The resulting thrombocytopenia reduces patient health-related quality of life (HRQOL). In a randomized, open-label, 52-week study of non-splenectomized ITP patients treated with romiplostim or medical standard of care (SOC), patients completed the 10-scale ITP-patient assessment questionnaire (PAQ) at the start of the study and after 12, 24, 36, 48,and 52 weeks of treatment. HRQOL changes were examined for all patients in both treatment groups and by responder status, splenectomy status, and after the use of rituximab. Patients in both groups showed marked increases in all HRQOL scales over 52 weeks of treatment.These change scores exceeded the minimally important difference values (a measure of clinical relevance) for most of these scales,especially in responders to treatment. Compared with baseline,patients receiving romiplostim showed statistically significant improvements compared to SOC over 52 weeks for the ITP-PAQ scales of Symptoms, Bother, Activity, Psychological Health, Fear, Overall QOL,and Social QOL. Overall, treatment of ITP was associated with improvement in HRQOL. Patients receiving romiplostim had greater HRQOL improvements than those receiving SOC, but the magnitude ofthe difference is of uncertain clinical benefit.

Romiplostim increases platelet counts and reduces the risk of bleeding in patients with immune thrombocytopenia (ITP). This post hoc analysis compared the effect of romiplostim versus medical standard of care (SOC) on clinically relevant bleeding-related episodes (BREs) in a 52-week open-label study of patients with ITP. BREs were defined as actual bleeding events and/or use of rescue medication. Nonsplenectomized adult patients with ITP were randomized to receive weekly subcutaneous injections of romiplostim (n = 157) or SOC (n = 77). The rate of all BREs (per 100 patient-weeks) was lower in patients treated with romiplostim (3.1) than in those treated with SOC (9.4); the relative rate (romiplostim/SOC) was 0.33 (95 % CI 0.27–0.40). The rate of BREs associated with immunoglobulin (Ig) rescue medication was also lower for romiplostim (0.2) than SOC (4.8); the relative rate (romiplostim/SOC) was 0.05 (95 % CI 0.03–0.08). BRE rates were lower in patients with platelet counts ≥50 × 109/L, and patients treated with romiplostim spent more time with platelet counts ≥50 × 109/L than did patients treated with SOC. Bleeding-related hospitalizations were rare in both groups. Thus, romiplostim treatment provided greater reductions in all BREs, as well as BREs involving Ig rescue medications, than did SOC.

OBJECTIVES:Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction, sub-optimal platelet production, and mild-to-severe bleeding. Nplate® (romiplostim), a thrombopoietin receptor agonist, and intravenous immunoglobulin (IVIg), an expensive and occasionally scarce blood product, are used in the treatment of ITP. The objective of this study was to compare the total cost of treating patients with romiplostim vs IVIg in Québec, Canada.METHODS:A net cost impact model was developed to calculate the annual cost of romiplostim compared with IVIg based on actual practice observations in all patients (n = 95) treated for chronic ITP with IVIg from April 2010 to March 2011 in two participating hospitals. The model included costs of: drug acquisition, drug preparation and administration, patient monitoring, and indirect costs. Healthcare practitioners were consulted regarding romiplostim and IVIg treatment algorithms and the resources involved in patient monitoring.RESULTS:The average annual drug acquisition costs of romiplostim and IVIg were $48,024 and $98,868, respectively. Lower costs for drug preparation and administration ($309 vs $1245) and less time lost from work ($256 vs $2086) were attributed to romiplostim. The cost of follow-up monitoring was the same for both romiplostim and IVIg ($121). The total average annual per patient costs for romiplostim vs IVIg were, respectively, $48,710 and $102,320. The use of romiplostim was projected to save, on average, almost $54,000 per patient per year.LIMITATIONS:The study was conducted in two hospitals in Québec. Romiplostim may show different cost savings in other hospitals and other provincial and national jurisdictions.CONCLUSIONS:Scarce blood products must be used wisely. Romiplostim can allow for improved healthcare resource allocation by reserving IVIg for use in other areas of greater need while also providing cost savings for the overall provincial healthcare budget.

Abstract Abstract 170 Introduction: Immune thrombocytopenia (ITP) is a hemorrhagic disorder characterized by low platelet counts, spontaneous bruising, mucosal bleeding, and intracranial hemorrhage. In children ≤ 15 years old, the ITP incidence rate is approximately 2–5 cases per 100,000 person-years, with 30% of such cases considered as chronic ITP, which is characterized by persistently low platelet counts for at least 12 months after initial diagnosis. The disease burden of chronic ITP has not been well studied. Herein, we utilized an all-payer inpatient care database for pediatric discharges in the US to examine resource utilization, costs, and important clinical outcomes in hospitalized children with a diagnosis of ITP. Methods: The 2006 Kids' Inpatient Database (KID) was selected for this analysis. The KID is developed within the Healthcare Cost and Utilization Project (HCUP) sponsored by the federal Agency for Healthcare Research and Quality (AHRQ). Systematic random sampling is used to select 80% of all non-birth pediatric discharges, 10% of all non-complicated births, and 80% of all complicated births from all participating community and non-rehabilitation hospitals for inclusion. The 2006 KID database contains data on over 3 million unweighted discharges collected from over 3,700 hospitals in 38 states. This large sample size enables analyses of relatively rare conditions, such as pediatric ITP. ITP-related discharges were identified with the ICD-9-CM diagnosis code of 287.31, regardless of whether it was the principal diagnosis. We developed national estimates of the following: average total inpatient cost; average length of stay (LOS); incidence rates of costly procedures such as total splenectomy and blood transfusions (through ICD-9 procedure codes); incidence rates of serious complications such as septicemia, bacteremia, intracranial hemorrhage (through hospital DRG codes), and in-hospital death. Hospital charges were converted to costs using hospital-specific cost-to-charge ratios available in the database. In addition, subgroup analyses by the following age groups were conducted: 1 to 5, 6 to 9, 10 to 13, and 14 to 17, as well as by whether the ICD-9 code for ITP was the primary diagnosis or a secondary diagnosis on the discharge summary. Results: Approximately 4,274 (0.26%) of all non-birth-related discharges among patients aged 1–17 were in patients with ITP, including 3,633 identified with ITP as the principal diagnosis and 641 as a secondary diagnosis. The majority of hospitalizations in ITP patients occurred in large, teaching hospitals, and slightly over half were for girls. Close to 50% of the ITP hospitalizations occurred through emergency room admissions or transfers from other hospitals or healthcare facilities. The overall incidence of intracranial hemorrhage among ITP hospitalizations was 0.43%, confirming earlier studies. Total splenectomy occurred in approximately 1 in 25 (4.3%) such hospitalizations. The mortality rate during ITP hospitalizations was 0.38%, compared to 0.23% for all other hospitalizations; the difference was not statistically significant. The average LOS for ITP hospitalizations was shorter than for all other hospitalizations in the KID (2.4 vs. 3.6 days, p < 0.0001), but no significant difference in mean total inpatient costs was noted ($6,869 for ITP vs. $6,515 for all others), indicating that the complexity of hospitalization, and correspondingly the intensity of treatment, might have been greater in patients with ITP. A higher complication rate, greater resource utilization, and total costs were all associated with increasing age, with the oldest pediatric age group (14–17 years) experiencing the highest rate of blood transfusions and total splenectomy, the longest LOS, and the greatest total costs (p < 0.0001 for all). Hospitalizations in which ITP was listed as a secondary diagnosis were associated with significantly greater resource use and total costs compared with those where ITP was the primary diagnosis (p < 0.0001). Conclusion: Although hospitalizations in pediatric patients with ITP were not associated with greater LOS or mortality, they appeared to be associated with a greater intensity of resource use and per-day cost. Older age and ITP as a secondary diagnosis contributed to longer stay, more resource use, and higher total cost during hospitalization. Disclosures: Lu: Amgen: Consultancy, Equity Ownership, Research Funding. Danese:Amgen: Consultancy, Research Funding. Herbert:Amgen: Consultancy, Research Funding. Eisen:Amgen: Employment, Equity Ownership. Deuson:Amgen: Employment, Equity Ownership.

Abstract Abstract 4209 Introduction: Immune thrombocytopenia (ITP) is characterized by low platelet counts, spontaneous bruising, mucosal bleeding, and, more seriously, intracranial hemorrhage. The disease is associated with a high risk of complications, often requiring visits to emergency departments (ED), with possible subsequent hospitalization. To date, information about ED visits in ITP patients, including frequency, cost, hospitalization risk, and mortality risk, has not been well documented, although such data are critical to the understanding of the clinical and financial implications of poorly-controlled, chronic ITP. We used the 2007 Nationwide Emergency Department Sample (NEDS) to examine resource utilization, ED visits, and hospitalization charges in the US. Methods: The 2007 NEDS contains about 27 million ED records from over 970 hospitals in 27 Healthcare Cost and Utilization Project (HCUP) Partner States, representing a 20% stratified sample of US hospital-based ED visits. The database includes hospital and patient characteristics, diagnoses and procedures, disposition from ED including hospitalization and mortality, discharge diagnosis-related group (DRG) for subsequent hospitalizations, and total charges. Its large sample size enables analyses of relatively rare conditions such as ITP. All ED visits in the database were separated into two groups: visits with ITP as one of the diagnoses (ICD-9-CM diagnosis code of 287.31), and those without a diagnosis of ITP. Outcomes and resource use were separately evaluated in these two groups, as well as in several subgroups within the ITP group defined by age and whether the ITP diagnosis was the primary or a secondary diagnosis. Results: Approximately 8,348 (∼0.03%) of all ED visits in the 2007 NEDS database were in patients with ITP (28% as the primary diagnosis), of which nearly 60% were by female patients and 88% by adult patients (≥18 years old). Medicare or Medicaid was listed as the primary payer in 58% of the visits. Seventy-five percent of the ED visits in ITP patients led to hospitalizations, compared with less than 16% of ED visits in non-ITP patients (p < 0.0001). In ITP patients, 3% of the ED visits ended in death, compared with 0.6% in non-ITP patients (p < 0.0001). The mean total charges for ED visits in ITP patients were $1,650 compared with $1,495 for all others (p<0.0001). The average length of stay (LOS) during hospitalizations subsequent to ED visits was >1.5 days longer (6.5 vs. 5.0 days; p < 0.0001) for ITP patients. The mean total combined charges during the ED visit and resulting hospitalization were >60% higher ($47,000 vs. $29,000; p < 0.0001) for ITP patients. Subgroup analyses of ED visits in ITP patients by age showed that in the majority of visits by pediatric patients (<18 years old), ITP was identified as the primary diagnosis (61%) compared with only 24% among visits by adult patients. Furthermore, visits by adult ITP patients were less likely to result in routine discharge (18% vs. 50%), more likely to result in hospitalization (80% vs. 43%), and were associated with higher mortality compared with pediatric ITP patients (4% vs. 0.1%; p < 0.0001 for all comparisons). ED visits identified with ITP as the primary diagnosis were associated with a higher rate of subsequent hospitalizations (81% vs. 73%), but lower total charges and mortality ($1,490 vs. $1,710, and 2% vs. 4%) respectively, compared with those identified with ITP as a secondary diagnosis (p < 0.0001 for all comparisons). Conclusion: ED visits in ITP patients were associated with significantly worse outcomes, higher resource utilization, and greater total charges. For patients with ITP, younger age and a primary diagnosis of ITP were generally associated with better outcomes following ED visits. More robust and rigorous analyses controlling for patient and hospital heterogeneities will be conducted to confirm these findings. Disclosures: Lu: Amgen: Consultancy, Equity Ownership, Research Funding. Danese:Amgen: Consultancy, Research Funding. Halperin:Amgen: Consultancy, Research Funding. Eisen:Amgen: Employment, Equity Ownership. Deuson:Amgen: Employment, Equity Ownership.

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 >= 50 x 10(9)/L, no outpatient bleed: 0.863 +/- 0.15; HS2: platelets >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.

Abstract Abstract 569 Introduction: Romiplostim, a novel peptibody that increases platelet production, is approved for the treatment of adult chronic ITP. Positive results from a previous study suggest the potential that romiplostim could improve QOL (Kuter, ASH 2009, #679). Immunosuppressive therapies for ITP may adversely affect patient QOL. We compared QOL between SOC- and romiplostim-treated pts from this study, and examined changes among subgroups of pts. Methods: This was an open-label study of nonsplenectomized ITP pts who were randomized to receive either once-weekly subcutaneous romiplostim or SOC. SOC treatments were prescribed according to standard institutional practices or therapeutic guidelines. QOL was assessed using the ITP patient assessment questionnaire (ITP-PAQ; consisting of 10 scales scored from 0–100); assessments were taken at baseline and every 12 weeks to week 52. Scores were also assessed for subgroups of pts with the following favorable outcomes: (1) did not receive blood transfusions or rescue medications, (2) did not experience bleeding ≥ grade 2, (3) did not experience a platelet count < 20 × 109/L. Mean and change from baseline scores were computed, and differences between treatment groups and among subgroups were assessed. Clinical significance was determined from the minimal important difference (MID), which is the smallest difference in QOL considered clinically meaningful (Mathias et al., CMRO 375-83) and corresponds to an 8–15 point improvement depending on the scale. The time to MID was also computed for Symptoms, Bother, Activity and Fatigue. Results: In total, 157 pts were randomized to receive romiplostim and 77 to receive SOC. At baseline, no statistically significant differences were found between the romiplostim and the SOC group on any of the scales. At 52-weeks, change scores for both the romiplostim group and the SOC group showed improvements that exceeded the MID with the exception of Fatigue in both arms and Activity in the SOC arm (Table). In comparison to the SOC group, the romiplostim group showed statistically significantly greater improvements from baseline for all scales except Fatigue. The differences between treatment groups did not exceed the MID for any of the scales. The time to MID was significantly shorter for the romiplostim group vs the SOC group on the Symptoms and Bother (p<0.0001), and Fatigue (p=0.0068) scales. Among subgroups with favorable clinical outcomes, statistically significantly greater improvements were seen in the romiplostim group compared with the SOC group in many of the scales. The difference between treatment groups exceeded the MID only once: romiplostim-treated pts in the subgroup who did not experience platelet counts < 20 × 109/L had a 12.6 point greater improvement in Activity score compared to SOC pts. Conclusions: Nonsplenectomized ITP pts receiving romiplostim had greater improvements in QOL than pts receiving SOC. These improvements were maintained even among subgroups of pts with favorable clinical outcomes. However, the open-label study design limits our ability to make conclusions, and the clinical significance of the QOL improvements in romiplostim-treated pts relative to those receiving SOC remains uncertain. Disclosures: Kuter: Amgen Inc.: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; ONO: Consultancy; Pfizer: Consultancy, Research Funding; Shionogi: Consultancy, Research Funding. Mandanas:Celgene: Honoraria; Genentech/Roche: Honoraria; Amgen Inc.: Honoraria; GlaxoSmithKline: Speakers Bureau; Pfizer: Speakers Bureau; Genomic Health: Speakers Bureau. Giagounidis:Celgene: Consultancy, Honoraria. Wang:Amgen Inc.: Employment, Equity Ownership. Mathias:Amgen Inc.: Consultancy. Deuson:Amgen Inc.: Employment, Equity Ownership.

Immune thrombocytopenic purpura (ITP) is associated with low platelet counts and, consequently, a high risk of adverse events leading to hospitalization. However, there are few data on the clinical and economic burden of hospitalizations for ITP. The Nationwide Inpatient Sample (NIS) database of discharges, a stratified 20% sample of all United States (US) community hospitals across all payers, was used to evaluate discharges in ITP patients. We developed nationally representative numbers of discharges in ITP patients from 2003 to 2006 based on diagnosis codes. Using appropriate weights for each NIS discharge, we created national estimates of average cost, length of stay, and in‐hospital mortality for specific groups of ITP‐related hospitalizations. Approximately 129,000 discharges occurred between 2003 and 2006 in ITP patients. The average cost associated with all discharges in 2008 dollars was 16,476, with a 6.4‐day length of stay and in‐hospital mortality of 3.8%. In contrast, the average cost of all hospitalizations in the US population during the same period was 10,039, the average length of stay was 4.8 days, and in‐hospital mortality was 2.5%. Mortality risk was higher for ITP patients than for the standard US population adjusted for age and gender, with a relative mortality ratio of 1.5 (95% CI: 1.4–1.6). On the basis of a nationally representative sample of US discharge records from 2003 to 2006, hospitalization with ITP represents an economically and clinically important event. ITP was associated with higher costs, longer stays, and more in‐hospital deaths on average than all other hospitalized patients combined. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.

Splenectomy is a common therapy for adults with chronic idiopathic thrombocytopenic purpura (ITP). Thisstudy was designed to estimate both the short-term surgical non-response rate and the long-term relapse rate after laparoscopic splenectomy. A systematic review was conducted of articles published between January 1, 1991 and January 1, 2008. Selection criteria included: chronic ITP, study enrollment in 1990 or later, > or =12 months of follow-up, > or =15 patients with ITP, > or =75% of patients at least 14 years of age, not HIV positive, not undergoing a second splenectomy, and type of performed splenectomy clearly reported. Data were pooled across studies to estimate rates. We identified 170 articles, of which 23 met our inclusion criteria (all observational studies). These studies represent 1,223 laparoscopic splenectomies (71 or 5.6% were converted to open splenectomy during surgery). The pooled short-term surgical non-response rate among the 18 studies reporting data was 8.2% (95% CI 5.4-11.0). The pooled long-term relapse rate across all 23 studies was 43.6 per 1,000 patient years (95% CI 28.2-67.2). This translates to an approximate failure rate of 28% at 5 years for all patients undergoing splenectomy. Studies with shorter durations of follow-up had significantly higher pooled relapse rates than studies with longer follow-up (P = 0.04). Laparoscopicsplenectomy is effective for most patients. Splenectomy may have higher initial relapse rates, particularly, in the first 2 years after surgery, and the rate may decline over time. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.

Abstract Abstract 891 Background: Chronic Immune thrombocytopenia (ITP) is characterized by low platelet counts and increased risk of bleeding. Rescue medications used to treat or prevent bleeding produce transient increases in platelet counts but may be associated with additional toxicities and costs. Romiplostim, approved for the treatment of adult chronic ITP, is a TPO mimetic peptibody protein that increases platelet production. Previously published data from phase 3 romiplostim trials showed that despite the increased use of rescue medication in the placebo arm, patient (pt) incidence of bleeding was reduced in the romiplostim arm vs placebo arm: 15% vs 34% (p = 0.02) for bleeding of grade ≥2 severity and 7% vs 12% (p=0.36) for grade ≥3 severity. Objective: To evaluate the effects of romiplostim treatment on bleeding outcomes in the phase 3 placebo controlled studies in chronic ITP pts with and without previous splenectomy. Bleeding events were captured as adverse events making it difficult to identify a single event reported multiple times versus persistent or recurrent bleeding. Further, we have developed a composite endpoint, termed bleeding-related episodes (BREs), which combines bleeding events and rescue medication administration to account for use of rescue medications to prevent bleeding. Methods: Adults with chronic ITP and a mean baseline platelet count <30 × 109/L were eligible. The previously published studies were conducted separately in splenectomized and nonsplenectomized populations. Pts were randomized (2:1) to receive romiplostim or placebo by subcutaneous injection once weekly for 24 weeks, with dose adjustments to maintain platelet counts between 50-200 × 109/L. Rescue medications were permitted to treat or prevent bleeding and included immunoglobulins, platelet transfusions, corticosteroids, or an increase in dose or frequency of a concurrent ITP medication. A BRE was defined as an actual bleeding event and/or the use of rescue medication. To collapse related events into episodes, events (bleeding events and/or the use of rescue medication) that occurred concurrently or within 3 days of each other were considered a single BRE. Bleeding events beginning 7 or more days after the start of the initial bleeding event were considered a new BRE. To account for differences in time spent on-study, rates of BRE per 100 pt-weeks were calculated. Results: A total of 125 pts (41 placebo, 84 romiplostim) were enrolled in the two studies. Baseline characteristics were well-balanced between the placebo and romiplostim-treated groups. During the treatment period, the rate of BREs was lower in the romiplostim group than in the placebo group, and results were consistent between splenectomized and nonsplenectomized pts (Table). Across both studies, the rate of BREs was reduced by 55% in pts receiving romiplostim compared to those receiving placebo (95% CI, 41% to 65%). BREs were more frequent at platelet counts <50 × 109/L (Table). BREs associated with hospitalizations were less common among romiplostim- than placebo-treated pts, and occurred at platelet counts <50 × 109/L in 10 of 11 cases. Corticosteroids (58 romiplostim, 38 placebo) and immunoglobulins (30 romiplostim, 73 placebo), were the most commonly used rescue medications and the rate of BREs including immunoglobulins was reduced by 88% in pts receiving romiplostim compared to placebo. Conclusions: In adults with chronic ITP, romiplostim was associated with a significant reduction in BREs compared to placebo. There was a marked reduction in BREs requiring immunoglobulins in the romiplostim arm compared to the placebo arm. Results were comparable in splenectomized and nonsplenectomized populations. The platelet count for a BRE starting ≥1 day after a platelet count measurement was calculated from the 2 proximal weekly measurements. Disclosures: Weitz: Amgen Inc.: Speakers Bureau. Sanz:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Henry:Amgen Inc.: Research Funding, Speakers Bureau; Orthobiotech: Research Funding, Speakers Bureau; Watson Pharma: Research Funding, Speakers Bureau. Schipperus:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees. Godeau:Amgen Inc.: Consultancy, Research Funding; Laboratoire Français de Fractionnement et de Biotechnologies (LFB): Consultancy; Roche: Research Funding. Gleeson:Amgen Inc.: Consultancy, Research Funding. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

Background: Corticosteroid (CS) therapy is effective in many patients with immune thrombocytopenic purpura (ITP), although it is associated with adverse effects.Objective: This study was conducted to describe the CS-related symptom experience of adult patients with ITP and to compare the symptom experience of current users of CS, previous users of CS, and those who have never used CS.Methods: In 2006, adult members of the Platelet Disorder Support Association (PDSA) who were listed in the organization's database, resided in the United States, and had a diagnosis of ITP were invited to participate in a Web-based survey. Symptom experience was assessed using 33 CS-related symptoms derived from a scale developed for use in patients undergoing organ transplantation. Symptom experience over the past 4 weeks was measured in terms of the occurrence of symptoms (rated on a 5-point scale from 1 [never occurring] to 5 [always occurring]) and the distress associated with those symptoms (rated on a 5-point Likert scale from 0 [not at all distressing] to 4 [extremely distressing]). Respondents were categorized according to 4 patterns of CS use: current users, nonusers, previous users who stopped CS use < 6 months earlier, and previous users who stopped CS use >= 6 months earlier.Results: The survey was completed by 985 patients with ITP (8.2% of the PDSA membership). The median age of the sample was 47 years, and the ratio of women to men was 3:1. One hundred sixteen patients (11.8%) were current CS users, 171 (17.4%) were nonusers, 99 (10.1%) had stopped CS use < 6 months earlier, and 599 (60.8%) had stopped CS use >= 6 months earlier. In all 4 groups, back pain, fatigue, sleep difficulties, muscle weakness, and difficulty seeing well were reported to be the most frequently occurring and most distressing symptoms. Current CS users and those who stopped CS treatment < 6 months earlier also reported bruises to be among their most frequent and distressing symptoms. Twenty-five of the 33 symptoms occurred more frequently in current CS users than in nonusers, and 30 symptoms occurred more frequently in current users than in previous users who had stopped CS use >= 6 months earlier. Symptom occurrence was significantly greater for current users compared with those who stopped CS use < 6 months earlier for puffy face (q = 0.003), excessive appetite (q = 0.002), changed facial features (q = 0.033), and buffalo hump (q = 0.048). Patients who had stopped CS use < 6 months earlier reported 20 of the 33 symptoms significantly more often than those who had stopped CS use >= 6 months earlier (q < 0.05). The only symptoms reported significantly more often in patients who had stopped CS use >= 6 months earlier compared with nonusers were buffalo hump and bruises (q < 0.05). The distress associated with bruises was significantly higher in current users compared with nonusers and compared with previous users who had stopped CS use >= 6 months earlier (both, q = 0.047). Current users also reported significantly greater distress than nonusers for puffy face and excessive appetite (both, q = 0.047). Changed facial features was significantly more distressing in current users compared with those who had stopped CS use >= 6 months earlier (q = 0.047).Conclusions: Different symptom profiles emerged based on the pattern of CS use. Patients who were currently using CS or who had stopped CS treatment < 6 months earlier reported more symptoms than did patients who had never received CS or who had stopped CS treatment >= 6 months earlier.

ITP is an autoimmune disease characterized by low platelet counts due to increased platelet destruction and inadequate platelet production. It is often a chronic disorder that requires long-term treatment. Current common treatment therapies for chronic ITP include corticosteroids, intravenous immunoglobulins (IVIG), rituximab, and anti-D antibody. Splenectomy may be required for those patients who do not respond or relapse after these medical therapies, or require intolerable doses to achieve safe platelet counts. Few studies have reported treatment pattern of current therapies for ITP. We report results of an international multi-center retrospective and prospective observational study of adult patients receiving treatments and/or splenectomy for chronic ITP. Patients with a diagnosis of ITP were enrolled from 100 community and academic centers. Date of 1st ITP diagnosis, treatments received and medical history were obtained retrospectively from patient chart data. ITP treatments, dose, response, and duration of response were collected prospectively for 12 months. Among 326 patients with ITP studied (mean age=54 years, male 40.2%), 24% received a splenectomy during this study. In patients who were not splenectomized (n=248), 77% received ITP medications with corticosteroids being the most frequently prescribed medication among patients who received 1 type of ITP treatment. IVIG was most frequently prescribed in patients who received 2 types of ITP treatments, and patients were most likely to receive a splenectomy after receiving 2 or more types of ITP treatments (table). In splenectomized patients, the average duration from ITP diagnosis to splenectomy was 2.79 years (n=74, SD=4.42, min=0, max=23.38). Prior to surgery, splenectomized patients were most likely to receive corticosteroids in patients receiving 1 type of treatment, and IVIG in patients receiving 2 types of ITP treatments. Following surgery, splenectomized patients were also most likely to receive corticosteroids in patients receiving 1 type of ITP medication, and rituximab in patients with 2 types of ITP medications. Overall, patients with ITP are exposed to numerous ITP treatments, among which, corticosteroids were most frequently used in both splenectomized and non-splenectomized patients. All patients receiving a splenectomy also required 1 or more ITP treatments following surgery. These results demonstrate that current ITP therapies are limited in efficacy and durability and often lead to patients receiving multiple types of ITP treatments. Novel ITP therapies with better efficacy and durable response are needed.

Splenectomy serves as a common therapy in treating adults with chronic ITP. Laparoscopic splenectomy was introduced in 1991 with the goal of reducing complication rates. This study was designed to estimate both the initial surgical non-response rate and the long-term relapse rate of splenectomy in the post-laparoscopic era. A systematic literature review was conducted by searching PubMed for articles published between January 1, 1991 and October 3, 2006. Selection criteria included: chronic ITP, study enrollment in 1990 or later, ≥12 months of follow-up, ≥15 patients with ITP, ≥75% of patients at least 14 years of age, not HIV positive, and not undergoing a second splenectomy. Response rates for surgery were collected according to an author-defined platelet response criterion (platelet counts <50x109/L or <30x109/L in 75% of studies). Relapse rates post-splenectomy (using the same platelet response criteria) were also collected. A meta-analysis was conducted to estimate a pooled surgical non-response rate as well as a pooled relapse rate in responders by weighting the study-specific estimates by the inverse of their variances, using Stata 9™. The pooled relapse rate was converted to a probability using the exponential formula, e(-rate x time). We identified 161 articles for detailed review. Of these, 24 met our inclusion criteria, all of which were observational studies. These studies represent 1,138 laparoscopic splenectomies (66 or 5.8% were converted to open splenectomy during surgery), and 317 open or undefined splenectomies. The average surgical non-response rate across 21 studies reporting data was 12.2% (95% CI: 10.3–14.3%). The average long-term relapse rate per person year across all studies was 53 per 1,000 patient years (95% CI: 45.0–62.0%). This corresponds to a 5% per year failure rate, or 32% failure rate after 5 years, for all patients initiating surgery. Initial non-response rate to planned splenectomy is 12% in adults with ITP. For patients undergoing laparoscopic splenectomy, 6% required conversion to open splenectomy. The 5 year relapse rate post-splenectomy is 32%. Splenectomy, although the current standard of care, is not always initially successful and does not provide a durable response in all patients. The benefits and risks of splenectomy must be weighed in light of newer options of therapy currently available.