Chronic Immune Thrombocytopenia In Adults Research Articles

Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center

Objective: This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects. Methods: A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments. Results: Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively (P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively (P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% (P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion: Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Avatrombopag for the Treatment of Adult Patients with Chronic Immune Thrombocytopenia (cITP): Focus on Patient Selection and Perspectives.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduced number of circulating platelets due to immune-mediated destruction and decreased platelet production in the bone marrow. Thrombopoietin receptor agonists (TPO-RAs) are highly effective and widely used in the treatment of patients with steroid treatment failure or dependency. Avatrombopag represents a new supplement to the TPO-RAs family. It was originally approved for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo an invasive procedure. However, labeled indications for avatrombopag have been relatively recently expanded to include treatment of chronic ITP in adults with insufficient response to the previous treatments. In this article, we provide an overview of pharmacodynamics and pharmacokinetics of avatrombopag as well as results of the clinical trials related to safety and efficacy of avatrombopag with a perspective on current clinical use. Available data so far suggests that avatrombopag can be effectively used in ITP patients and has a favorable safety profile. Though further studies are needed to affirm the efficacy and safety, avatrombopag has the potential to become a TPO agonist of choice for many patients with ITP.

A landscape for drug-target interactions based on network analysis.

In this work, we performed an analysis of the networks of interactions between drugs and their targets to assess how connected the compounds are. For our purpose, the interactions were downloaded from the DrugBank database, and we considered all drugs approved by the FDA. Based on topological analysis of this interaction network, we obtained information on degree, clustering coefficient, connected components, and centrality of these interactions. We identified that this drug-target interaction network cannot be divided into two disjoint and independent sets, i.e., it is not bipartite. In addition, the connectivity or associations between every pair of nodes identified that the drug-target network is constituted of 165 connected components, where one giant component contains 4376 interactions that represent 89.99% of all the elements. In this regard, the histamine H1 receptor, which belongs to the family of rhodopsin-like G-protein-coupled receptors and is activated by the biogenic amine histamine, was found to be the most important node in the centrality of input-degrees. In the case of centrality of output-degrees, fostamatinib was found to be the most important node, as this drug interacts with 300 different targets, including arachidonate 5-lipoxygenase or ALOX5, expressed on cells primarily involved in regulation of immune responses. The top 10 hubs interacted with 33% of the target genes. Fostamatinib stands out because it is used for the treatment of chronic immune thrombocytopenia in adults. Finally, 187 highly connected sets of nodes, structured in communities, were also identified. Indeed, the largest communities have more than 400 elements and are related to metabolic diseases, psychiatric disorders and cancer. Our results demonstrate the possibilities to explore these compounds and their targets to improve drug repositioning and contend against emergent diseases.

Thrombopoietin receptor agonist for treatment of immune thrombocytopenia in pregnancy: a narrative review.

The treatment of immune thrombocytopenia (ITP) in adults has evolved rapidly over the past decade. The second-generation thrombopoietin receptor agonists (TPO-RAs), romiplostim, eltrombopag, and avatrombopag are approved for the treatment of chronic ITP in adults. However, their use in pregnancy is labeled as category C by the United States Food and Drug Administration (FDA) due to the lack of clinical data on human subjects. ITP is a common cause of thrombocytopenia in the first and second trimester of pregnancy, which not only affects the mother but can also lead to thrombocytopenia in the neonatal thrombocytopenia secondary to maternal immune thrombocytopenia (NMITP). Corticosteroids, intravenous immunoglobulins (IVIGs) are commonly used for treating acute ITP in pregnant patients. Drugs such as rituximab, anti-D, and azathioprine that are used to treat ITP in adults, are labeled category C and seldom used in pregnant patients. Cytotoxic chemotherapy (vincristine, cyclophosphamide), danazol, and mycophenolate are contraindicated in pregnant women. In such a scenario, TPO-RAs present an attractive option to treat ITP in pregnant patients. Current evidence on the use of TPO-RAs in pregnant women with ITP is limited. In this narrative review, we will examine the preclinical and the clinical literature regarding the use of TPO-RAs in the management of ITP in pregnancy and their effect on neonates with NMITP.

Clinical Outcomes in Patients with Immune Thrombocytopenia Treated with All 3 Approved Thrombopoietin Receptor Agonists

Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by a platelet count &amp;lt; 100 x 109 / L due to accelerated platelet destruction and impaired platelet production (McMillan 1981). At present, there are 3 available thrombopoietin receptor agonists (TPO-RAs) approved for treatment of chronic ITP in adults. All three agents have high response rates, 40-90%, depending on the criteria used to define response (Ghanima et al 2019). Previous studies illustrate efficacy of Romiplostim and Eltrombopag having surprisingly high response rates when switching from one to the other, particularly if there was a response to the first TPO-RA (Gonzalez-Porras et al 2015; Lakhwani et al 2017; Cantoni et al 2018) but no studies have compared all 3 approved TPO-RA. Herein we describe 7 patients with difficult to treat chronic ITP who received all 3 TPO-RA and assess responses of the 7 to each of Eltrombopag, Romiplostim and Avatrombopag. Methods This was a retrospective review of all patients with chronic ITP seen at the Platelet Disorders Program at Weill Cornell Medicine-NY Presbyterian Hospital between July 2019 (following FDA approval of Avatrombopag) and June 2020 who had been treated with Eltrombopag, Romiplostim and Avatrombopag. Seven patients were identified (most had been followed for many years) and information collected on demographics, laboratory results, and clinical data including response and tolerance to ITP treatments, in particular the 3 TPO-RA. Results There were 4 females and 3 males with median age of 64 years (range 33-77). All had primary ITP with median 3 (range 2-13) separate ITP treatments, including investigational therapies, preceding treatment with their first TPO-RA (Table 1). All 7 patients had difficult to treat ITP with episodes of severe thrombocytopenia despite chronic treatments, requiring periodic rescue with IVIg and/or steroids. Three patients received Eltrombopag as their first TPO-RA and 4 patients Romiplostim. All 7 patients received Avatrombopag as their third TPO-RA and all also received other therapies either in conjunction with or in between TPO-RAs (Figure 1). No patient went directly from one TPO-RA to another without intervening treatment. All 7 patients (100%) responded to their first TPO-RA. For the 3 initially on Eltrombopag, duration of treatment ranged from 1 week to 8 years. When these 3 were switched to Romiplostim as a second TPO-RA, they responded with median time on treatment 27 months (range 21-48 months). Reasons prompting the switch from Eltrombopag to Romiplostim included: lost response (1), allergic reaction (1), insurance/financial issues (1). The 4 patients who started with Romiplostim had a median duration on treatment of 18 months (range 4-96 months). Two of these 4 who switched to Eltrombopag as their second TPO-RA responded to Eltrombopag with median time on treatment 5.5 months. Reasons for switching from Romiplostim to Eltrombopag included: unstable platelet response (2), patient preference for an oral agent (2). Prior to taking Avatrombopag, 5 patients returned to a TPO-RA they had previously responded to with 3 requiring higher doses on re-exposure. These patients (4, 6, 7) had switched from that initial agent due to patient preference (1), financial issues (1) and unstable platelet response (1). Five/7 patients (71%) responded to the third TPO-RA, Avatrombopag. Reasons prompting the switch to Avatrombopag from the previous TPO-RA included: patient preference (4), lost response (2), unclear/suboptimal response (1). The 5 responders remain on only Avatrombopag with durations of 3 months to 11 months. Conclusions: All 7 patients responded initially to TPO-RA whereas response rates of around 70% were seen when patients are switched to a second and subsequent third TPO-RA; response was very good to all 3 agents without clear preference of one over the others. Responders to distinct second and third TPO-RAs included patients who switched due to lack of response to a preceding TPO-RA as well as those who switched due to preference (for an oral agent without dietary restrictions) or intolerance/side effects. Loss of response to one TPO-RA should not preclude trying another. Patients may not respond as well on re-exposure to a previously seen TPO-RA; hence, ideally treatment would be maintained if possible with the initial agent. Disclosures Bussel: RallyBio: Consultancy; Momenta: Consultancy; Dova: Consultancy; 3SBios: Consultancy; Regeneron: Consultancy; Principia: Consultancy; Rigel: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Argenx: Consultancy; UCB: Consultancy; CSL Behring: Consultancy; Shionogi: Consultancy.

Fostamatinib, a Spleen Tyrosine Kinase (SYK) Inhibitor, for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): Final Results of the Phase 2, Multicenter, Open-Label Study

Fostamatinib, a Spleen Tyrosine Kinase (SYK) Inhibitor, for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): Final Results of the Phase 2, Multicenter, Open-Label Study

Comparison of treatments for persistent/chronic immune thrombocytopenia: a systematic review and network meta-analysis

Recent studies have indicated that medical options without splenectomy, such as rituximab (RTX) or thrombopoietin receptor agonists (TPO-RAs), can be effective to treat persistent or chronic primary immune thrombocytopenia (ITP). However, it remains to be determined which of these strategies should be the first choice after the first-line treatment for newly diagnosed ITP. We performed a systematic review and network meta-analysis to establish a clinically meaningful hierarchy of the efficacy and safety of medical treatments for persistent or chronic ITP in adults. Randomized controlled trials (RCTs) evaluating medical treatments were included. Reviewers independently extracted data and assessed the risk of bias. The main outcome was the overall response (platelet≥ 50 × 109/L); incidence of bleeding episodes, necessity of rescue treatments, and therapy-related adverse events including thrombosis were the secondary endpoints. A total of 12 randomized controlled trials (N= 1306) were included in this study. Our main finding was an improved overall response in TPO-RA arms (both Eltrombopag and Romiplostim) compared with that of RTX or placebo. There were no significant differences between Eltrombopag and Romiplostim. Moreover, clinically significant bleeding episodes were decreased in TPO-RA arm compared with placebo. Therapy-related adverse events showed similar profiles, and were tolerable in all treatment arms. In conclusion, TPO-RAs can be first choices for the treatment of persistent and chronic ITP, rather than RTX, as alternatives to splenectomy. Future head-to-head trials including TPO-RAs vs. RTX or Eltrombopag vs. Romiplostim are necessary to validate our study findings and determine the most suitable therapy for persistent/chronic ITP.

Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients

AbstractWe conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m2 and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician’s preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 109/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.

Integrated Analysis of Long Term Safety in Patients (pts) with Chronic Immune Thrombocytopenia (ITP) Treated with Romiplostim.

AbstractAbstract 2185 Introduction:ITP is characterized by low platelet counts due to increased platelet destruction and suboptimal platelet production. Romiplostim, which is approved for the treatment of chronic ITP in adults, is an Fc-peptide fusion protein (peptibody) that binds and activates the thrombopoietin receptor to stimulate platelet production. Results from a safety analysis of pooled data from ITP romiplostim clinical studies were previously reported (Rodeghiero et al, Haematologica 2010;95(s2) abstr 0184). Here we update the safety findings with the most inclusive clinical dataset of patients (pts) with ITP. Methods:Data from 13 studies of ITP were analyzed. Pts received romiplostim, placebo or medical standard of care (SOC) treatment at some time from July 2002 to June 2011. Data from the placebo/SOC arms were pooled. Results were adjusted for study duration and reported as rates per 100 patient-years (pt-yr) to reflect the unequal study time between pts given romiplostim and pts given placebo/SOC. In cases where pts enrolled in ≥ 1 study, data from the first and extension studies were combined. Data for pts who started on placebo/SOC and then received romiplostim were recorded as follows: data before pts received the first dose of romiplostim were included in the placebo/SOC group; data on or after the first dose of romiplostim were included in the romiplostim group regardless of any subsequent change in treatment. Results:Pts (N = 1,059) were mostly female (61%) and white (85%); 23 pediatric pts were included in the analysis. All pts had received prior ITP treatment per protocol entry criteria. Age, sex, race and prior ITP treatment were similar between groups. In studies where prior information on splenectomy was collected, 47% of pts had a splenectomy. Mean baseline platelet count: 21×109/L (standard deviation, 17×109/L). In total 921 pts received romiplostim, 65 received placebo/SOC, and 73 received placebo/SOC in the first study and romiplostim in subsequent studies. Mean weekly romiplostim dose: 4.2 μg/kg. Patient exposure to romiplostim: ≤ 1 yr, 47%; >1–2 yr, 26%; >2–3 yr, 15%; >3–4 yr, 6%; > 4 yr, 6%. Nineteen percent and 22% of pts who received romiplostim and placebo/SOC, respectively, did not complete participation in their first ITP study. Adverse events (AE) were reported in 94.2% and 93.5% of pts in the romiplostim and placebo/SOC groups, respectively. Most frequently reported AE (rates per 100 pt-yr) in the romiplostim vs placebo/SOC groups: headache (61 vs 58), contusion (48 vs 50) and epistaxis (35 vs 53). AE with > 10% difference in the romiplostim vs placebo/SOC groups: headache (36% vs 24%), arthralgia (24% vs 12%), nausea (20% vs 9%). Three pts developed neutralizing antibodies to romiplostim but did not develop neutralizing antibodies to thrombopoietin and did not become refractory to romiplostim. The Table summarizes AE.Romiplostim N = 994 pt-yr = 1,520Placebo/SOC N =138 pt-yr = 110nrate per 100 pt-yr95% CInrate per 100 pt-yr95% CISummary of AEAll AE17,1291,1271,110-1,1441,2681,1521,090-1,218Serious AE9106056-641079780-118Fatal AE4032-4873-14Treatment-Related AE1,739114109-120168153131-178Treatment-Related Serious AE11886-9181610-26Treatment-Related Fatal AE50.30.1-0.8000-3AE of InterestHemorrhage EventsAny grade3,115205198-212289263233-295Grade ≥ 31821210-14191710-27Thrombotic Events83a54-76b52-12Bone Marrow Reticulin Eventsc1511-2000-3Solid Tumor Events3422-3441-9Hematopoietic Malignancies/MDS Events7d0.50.2-13e31-8aForty-four events occurred within the first 6 months of treatment, of which 9 were arterial events.bOne event occurred within the first 6 months of treatment, which was an arterial event.cBone marrow biopsies were performed per investigators' discretion. Analysis excludes study 20080009 because bone marrow evaluations were collected differently than in other studies. Romiplostim, N = 825, pt-yr = 1,388; placebo/SOC, N = 138.dIncludes 1 event each of lymphoma, B-cell lymphoma and non-Hodgkin lymphoma.eIncludes 1 event of lymphoma. CI, confidence interval; MDS, myelodysplastic syndrome; n, number of events; pt-yr, total patient yr on study. Conclusions:This integrated analysis of all available clinical studies to date involving the use of romiplostim in ITP provides long term safety information with some pts receiving romiplostim for over five yr. The AE profile was consistent with previously reported studies. Disclosures:Cines:GlaxoSmithKline: Consultancy; Amgen Inc.: Consultancy; Eisai: Consultancy. Gernsheimer:Amgen Inc.: Consultancy, Honoraria; Symphogen: Consultancy; Laboratorios Raffo SA: Honoraria; Clinical Options: Consultancy; Hemedicus Corporation: Honoraria; Glaxo-Smith Kline: Consultancy; Shionogi: Research Funding; Cangene: Consultancy. Wasser:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Altomare:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wang:Amgen Inc.: Employment, Equity Ownership. Woodard:Amgen Inc.: Employment, Equity Ownership.

Comparing the Cost Per Treatment Success of Thrombopoietin Receptor Agonists to Watch & Rescue for the Treatment of Primary Adult Chronic Immune Thrombocytopenia (ITP) in the US

AbstractAbstract 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.

Final Results from an International, Multi-Center, Single-Arm Study Evaluating the Safety and Efficacy of Romiplostim in Adults with Primary Immune Thrombocytopenia (ITP),

Abstract 3279▪▪This icon denotes a clinically relevant abstract Background:ITP is an autoimmune disorder characterized by increased platelet destruction and suboptimal platelet production. Romiplostim stimulates platelet production via the TPO-receptor, and is recommended for second- and third-line treatment of chronic ITP in adults. We report final data from a large prospective study of romiplostim in adults with ITP of varying duration and severity. Methods: Eligibility criteria were broad: patients ≥18 years of age, who had received prior ITP therapies (final protocol amendment: ≥1, previous amendments: ≥3), with low platelet counts (final amendment: ≤ 30 × 109/L, previous amendments: ≤ 10, ≤ 20 × 109/L) or experiencing uncontrolled bleeding. The only excluded comorbidities were: hematological malignancy, myeloproliferative neoplasms, MDS and bone marrow stem cell disorder. Romiplostim was initiated at 1 (final amendment) or 3 (previous amendments) μg/kg/week, with dose adjustments allowed to maintain platelet counts ≥50 × 109/L. Patients could continue on study until they had access to commercially available romiplostim. Rescue medications were allowed at any time; concurrent ITP therapies could be reduced when platelet counts were > 50 × 109/L. Primary endpoint was incidence of adverse events (AEs) and antibody formation. Secondary endpoint was platelet response, defined as either (1) doubling of baseline count and ≥ 50 × 109/L or (2) ≥20 × 109/L increase from baseline. Results: A total of 407 patients received romiplostim, 60% of whom were female. Median (Q1, Q3) time since ITP diagnosis was 4.25 (1.20, 11.40) years (maximum 57.1 years), with 51% of patients splenectomised and 39% receiving baseline concurrent ITP therapies. Seventy-one percent of patients completed the study, with requirement for alternative therapy and withdrawn consent the most common reasons for discontinuation (5% each). Median (Q1, Q3) on-study treatment duration was 44.29 (20.43, 65.86) weeks (maximum 201 weeks), with a total of 20,201 subject-weeks on study. Incidence and type of AEs were consistent with previous studies. The most common serious treatment-related AEs were cerebrovascular accident, headache, bone marrow reticulin fibrosis (with no evidence of positive trichrome staining for collagen and no evidence suggesting primary idiopathic myelofibrosis), nausea, deep vein thrombosis, hemorrhage and pulmonary embolism, with each reported in 2 of 407 (0.5%) patients. All other serious treatment-related AEs were each reported in one patient. Eighteen patients died; 3 deaths (hemolysis, intestinal ischaema, aplastic anemia) were considered treatment-related. No neutralizing antibodies to romiplostim or TPO were reported. Approximately 90% of patients achieved each of the platelet response definitions, regardless of splenectomy status. Overall, median (Q1, Q3) time to response was 2 (1, 4) weeks for response definition 1, and 1 (1, 3) week for response definition 2. Median (Q1, Q3) baseline platelet count was 14 (8, 21) × 109/L. After 1 week of treatment median (Q1, Q3) platelet count had increased to 42 (18, 101) × 109/L. From week 8 onwards, and excluding counts within 8 weeks of rescue medication use, median platelet counts were consistently above 100 × 109/L (range 101.0–269.5 × 109/L). Median (Q1, Q3) average weekly romiplostim dose was 3.62 (1.99, 6.08) μg/kg. Summary/conclusions: This is the largest prospective study in adult ITP reported to date. The data reported here are similar to those reported for previous romiplostim studies, with romiplostim able to safely induce a rapid platelet response in adult ITP patients with low platelet counts or bleeding symptoms. Romiplostim is an important, well-tolerated, treatment option for adult ITP patients, which significantly increases and maintains platelet counts.Adverse Event Subject IncidenceN=407n (%)All AEs377 (93)Most common AEsHeadache119 (29)Arthralgia80 (20)Fatigue75 (18)Nausea72 (18)Epistaxis70 (17)Nasopharyngitis69 (17)Petechiae63 (16)Contusion62 (15)Serious AEs122 (30)Treatment-related AEs193 (47)Serious, treatment-related AEs29 (7)Platelet ResponseSplenectomisedNon-splenectomisedOverallN = 208N = 199N = 407n (%)n (%)n (%)Subjects achieving a doubling of baseline platelet count and a count ≥50 × 109/L183 (88)187 (94)370 (91)95% CI(83, 92)(90, 97)(88, 94)Subjects achieving a ≥20 × 109/L increase from baseline191 (92)189 (95)380 (93)95% CI(87, 95)(91, 98)(90, 96) Disclosures:Janssens:Amgen: Consultancy; Roche: Speakers Bureau; GSK: Membership on an entity’s Board of Directors or advisory committees. Tarantino:Cangene corporation: Research Funding; Baxter: Research Funding; Talecris: Honoraria, Speakers Bureau; Up-to-date: Patents & Royalties; The Bleeding and Clotting Disorders Institute: Board Member. Bird:Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity’s Board of Directors or advisory committees. Boccia:Amgen: Equity Ownership, Honoraria, Speakers Bureau. Lopez-Fernandez:Amgen: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Kozak:Amgen: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Steurer:Amgen: Honoraria. Dillingham:Amgen Limited: Employment, Equity Ownership. Lizambri:Amgen: Employment, Equity Ownership.

Intravenous Immune Serum Globulin in Immune Thrombocytopenia: Clinical Results and Biochemical Evaluation

Intravenous gamma-globulin of the pH 4-treated Swiss Red Cross (SRC) preparation is an effective therapy for acute and chronic immune thrombocytopenia (ITP) of childhood and chronic ITP in adults. Patients who may respond satisfactorily to treatment include those without detectable immune complexes and those with poor response to pretreatment. Results are especially good in children, half of whom with chronic conditions are able to discontinue therapy.

Intravenous Immune Serum Globulin in Immune Thrombocytopenia: Clinical Results and Biochemical Evaluation

Intravenous gamma-globulin of the pH 4-treated Swiss Red Cross (SRC) preparation is an effective therapy for acute and chronic immune thrombocytopenia (ITP) of childhood and chronic ITP in adults. Patients who may respond satisfactorily to treatment include those without detectable immune complexes and those with poor response to pretreatment. Results are especially good in children, half of whom with chronic conditions are able to discontinue therapy.