Melissa Eisen

Long-Term Use of the Thrombopoietin-Mimetic Romiplostim in Children With Severe Chronic Immune Thrombocytopenia (ITP)

Treatment of chronic severe pediatric ITP is not well studied. In a phase 1/2 12–16‐week study, 15/17 romiplostim‐treated patients achieved platelet counts ≥50 × 109/L, and romiplostim treatment was well tolerated. In a subsequent open‐label extension (≤109 weeks), 20/22 patients received romiplostim; all achieved platelet counts >50 × 109/L. Twelve patients continued in a second extension (≤127 weeks). Longitudinal data from start of romiplostim treatment through the two extensions were evaluated to investigate the safety and efficacy of long‐term romiplostim treatment in chronic severe pediatric ITP.

Case study of remission in adults with immune thrombocytopenia following cessation of treatment with the thrombopoietin mimetic romiplostim

Objectives: In adults, immune thrombocytopenia (ITP), characterized by platelet counts <100 × 109/l, is typically chronic, with remission reported infrequently ≥3 years post-diagnosis. The thrombopoietin mimetic romiplostim increases platelet counts and reduces use of concomitant ITP medications in chronic ITP. While often perceived as a long-term treatment, dose-adjustment rules allow romiplostim to be discontinued when hemostatic platelet counts are reached, as reported in Amgen trials. Methods: Eight romiplostim trials were examined for remission, defined as ≥26 consecutive weeks of platelets ≥50 × 109/l without treatment. Results: Remission was identified in 27 patients; median (quartile 1 [Q1], quartile 3 [Q3]) ITP duration of 2.1 (0.5, 4.2) years, 17/27 (63%) having ITP for >1 year, mean baseline platelets 20.9 × 109/l, median preremission maximum dose 3.0 µg/kg, 12/27 (44%) were splenectomized at baseline, and there were 40–276 cumulative weeks of romiplostim with median time to remission 7.1 months. Discussion/Conclusion: No clear-cut predictors of remission were apparent; however, a number of patients had ITP for <1 year and received romiplostim for <1 year.

A Phase 3, Randomized, Double‐Blind, Placebo‐Controlled Study to Determine the Effect of Romiplostim on Health‐Related Quality of Life in Children with Primary Immune Thrombocytopenia and Associated Burden in Their Parents

Chronic immune thrombocytopenia (ITP) in children can negatively impact their health‐related quality of life (HRQoL) and impose a burden on their parents. This study sought to examine the effect of romiplostim on HRQoL and parental burden in children with primary ITP.

Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia

Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet destruction and insufficient platelet production without another identified underlying disorder. Splenectomy may alter responsiveness to treatment and/or increase the risk of thrombosis, infection, and pulmonary hypertension. The analysis herein evaluated the safety and efficacy of the thrombopoietin receptor agonist romiplostim in splenectomized and nonsplenectomized adults with primary immune thrombocytopenia. Data were pooled across 13 completed clinical studies in adults with immune thrombocytopenia from 2002–2014. Adverse event rates were adjusted for time of exposure. Results were considered different when 95% confidence intervals were non-overlapping. Safety was analyzed for 1111 patients (395 splenectomized; 716 nonsplenectomized) who received romiplostim or control (placebo or standard of care). At baseline, splenectomized patients had a longer median duration of immune thrombocytopenia and a lower median platelet count, as well as a higher proportion with >3 prior immune thrombocytopenia treatments versus nonsplenectomized patients. In each treatment group, splenectomized patients used rescue medications more often than nonsplenectomized patients. Platelet response rates (≥50×109/L) for romiplostim were 82% (310/376) for splenectomized and 91% (592/648) for nonsplenectomized patients (P<0.001 by Cochran-Mantel-Haenszel test). Platelet responses were stable over time in both subgroups. Exposure-adjusted adverse event rates were higher for control versus romiplostim for both splenectomized (1857 versus 1226 per 100 patient-years) and nonsplenectomized patients (1052 versus 852 per 100 patient-years). In conclusion, responses to romiplostim were seen in both splenectomized and nonsplenectomized patients, and romiplostim was not associated with an increase in the risk of adverse events in splenectomized patients. clinicaltrials.gov Identifier: 00111475(A)(B), 00117143, 00305435, 01143038, 00102323, 00102336, 00415532, 00603642, 00508820, 00907478, 00116688, and 00440037.

Hospitalizations in pediatric patients with immune thrombocytopenia in the United States

Abstract To examine utilization and outcomes in pediatric immune thrombocytopenia (ITP) hospitalizations, we used ICD-9 code 287.31 to identify hospitalizations in patients with ITP in the 2009 HCUP KID, an all-payer sample of pediatric hospitalizations from US community hospitals. Diagnosis and procedure codes were used to estimate rates of ITP-related procedures, comorbidity prevalence, costs, length of stay (LOS), and mortality. In 2009, there were an estimated 4499 hospitalizations in children aged 6 months–17 years with ITP; 43% in children aged 1–5 years; and 47% with emergency department encounters. The mean hospitalization cost was

Appropriateness of granulocyte colony-stimulating factor use in patients receiving chemotherapy by febrile neutropenia risk level

5398, mean LOS 2.0 days, with 0.3% mortality (n = 13). With any bleeding (15.2%, including gastrointestinal 2.0%, hematuria 1.3%, intracranial hemorrhage [ICH] 0.6%), mean hospitalization cost was

Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study

7215, LOS 2.5 days, with 1.5% mortality. For ICH (0.6%, n = 27), mean cost was

Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies

40 209, LOS 8.5 days, with 21% mortality. With infections (14%, including upper respiratory 5.2%, viral 4.9%, bacterial 1.9%), the mean cost was

A Randomized, Double-Blind, Placebo-Controlled Phase 1/2 Study to Determine the Safety and Efficacy of Romiplostim in Children with Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP).

6928, LOS 2.9 days, with 0.9% mortality. Septic shock was reported in 0.3% of discharges. Utilization included immunoglobulin administration (37%) and splenectomies (2.3%). Factors associated with higher costs included age >6 years, ICH, hematuria, transfusion, splenectomy, and bone marrow diagnostics (p < 0.05). In conclusion, of the 4499 hospitalizations with ITP, mortality rates of 1.5%, 21%, and 0.9% were seen with any bleeding, ICH, and infection, respectively. Higher costs were associated with clinically significant bleeding and procedures. Future analyses may reveal effects of the implementation of more recent ITP guidelines and use of additional treatments.

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of Romiplostim in Children with Immune Thrombocytopenia (ITP)

Objective Inappropriate granulocyte colony-stimulating factor use with myelosuppressive chemotherapy has been reported. Using the Oncology Services Comprehensive Electronic Records electronic medical record database, prophylactic granulocyte colony-stimulating factor (pegfilgrastim/filgrastim) use in cancer patients was assessed by febrile neutropenia risk level. Methods Patients with nonmetastatic or metastatic breast, head/neck, colorectal, ovarian/gynecologic, lung cancer, or non-Hodgkin’s lymphoma who received myelosuppressive chemotherapy from June 2013 to May 2014 were included. Prophylactic granulocyte colony-stimulating factor use with high-risk, intermediate-risk, and low-risk chemotherapy and distribution of National Comprehensive Cancer Network risk factors with intermediate-risk regimens were assessed. Results Overall, 86,189 patients received ∼4.2 million chemotherapy cycles (high risk, 9%; intermediate risk, 48%; low risk, 43%). Prophylactic granulocyte colony-stimulating factor was given in 24% of cycles (high risk, 59%; intermediate risk, 29%; low risk, 11%). For nonmetastatic solid tumors, granulocyte colony-stimulating factor was given in 78% (high risk), 31% (intermediate risk), and 6% (low risk) of cycles. For metastatic solid tumors or non-Hodgkin’s lymphoma, granulocyte colony-stimulating factor was given in 50% (high risk), 27% (intermediate risk), and 11% (low risk) of cycles. Among patients receiving intermediate-risk regimens with granulocyte colony-stimulating factor, febrile neutropenia risk factors were identified in 56% (95% confidence interval, 51.1–60.9%) of patients with nonmetastatic solid tumors (n = 400) and in 70% (64.5–73.5%) of patients with metastatic solid tumors or non-Hodgkin’s lymphoma (n = 400). Conclusion Prophylactic granulocyte colony-stimulating factor use was appropriately highest for high-risk regimens and lowest for low-risk regimens yet still potentially underused in high risk regimens, overused in low-risk regimens, and not appropriately targeted in intermediate-risk regimens, indicating a need for further education on febrile neutropenia risk evaluation and appropriate granulocyte colony-stimulating factor use.