By Becky McCall
Medscape Medical News
June 12, 2009 (Berlin, Germany) — The platelet-stimulating drug romiplostim (Nplate) prevents a significant number of splenectomies in patients with immune thrombocytopenia (ITP), according to phase?3 study data presented here at the 14th Congress of the European Hematology Association.
Results show that 8% of patients taking the trial drug underwent surgery, compared with 35% of patients treated with standard-of-care (SOC) therapies (odds ratio, 0.17; 95% confidence interval [CI], 0.06 - 0.36). Treatment failure, another primary end point, occurred in 12% of patients in the romiplostim group, compared with 27% of the SOC group (odds ratio, 0.37; 95% CI, 0.12 - 0.74).
Mathias Rummel, MD, from Justus-Liebig University in Giessen, Germany, who led the study, said previous long-term data comparing romiplostim and placebo showed successful treatment of ITP for more than 4 years, but this new study was clinically more meaningful. "It compares the drug against the main standard-of-care treatments rather than placebo, and shows that romiplostim can prevent splenectomies in many patients."
Romiplostim was recently approved for treatment for chronic ITP in the United States, the European Union, Canada, and Australia on the basis of results from a placebo-controlled study and long-term extension studies. Dr. Rummel concluded that longer-term results, over 52 weeks in this analysis, were eagerly awaited.
In the trial, 234 patients were treated either with romiplostim or SOC therapies, such as cyclosporine, rituximab, azathioprine, and corticosteroids. Dr. Rummel noted that 42% of patients in the SOC group and 36% in the romiplostim group had received more than 3 previous ITP therapies. At baseline, patients randomized to romiplostim had a median platelet count of 27?× 109/L, whereas those randomized to SOC had a median platelet count of 33?× 109/L.
Over a 52-week period, romiplostim 3?μg/kg was administered subcutaneously once weekly, with dose adjustments based on platelet counts. Treatment failure was defined as a platelet count of 20?× 109/L or less at the highest recommended dose of romiplostim or SOC, a major bleeding event, or a change in therapy owing to adverse effects or intolerable symptoms.
Romiplostim, an engineered protein that combines the benefits of peptides and antibodies, stimulates platelet production at the thrombopoietin receptor. Similar to the natural growth factor thrombopoietin, romiplostim helps the proliferation and differentiation of cells in the bone marrow, boosting platelet counts.
Current SOC therapies address the destruction of platelets by the immune system but do little to increase platelet production. "The success of romiplostim in treating ITP has led us to rethink the pathophysiology of the disease. Historically, it was considered a disease of platelet destruction by autoantibodies, but now it is thought that reduced platelet production is equally important," Dr. Rummel told Medscape Oncology.
Safety in the romiplostim group was found to be similar to that in the SOC group. Serious treatment-related adverse events occurred in 7% of SOC patients and in 5% of romiplostim patients. In particular, bleeding events were experienced by 52% of the SOC group and 49% of the romiplostim group; bleeding events of grade?3 or above were seen in 8% and 3%, respectively; and thrombotic events were seen in 3% and 4%, respectively.
James Bussel, MD, from Weill Cornell Medical College in New York City, pointed out that these results suggest benefits for patients and providers. "These results describing avoidance of splenectomy in patients receiving romiplostim illustrate specific utility of treatment with this thrombopoietic agent. In addition to improvement in health-related quality of life, the avoidance of splenectomy provides a huge offset in cost for the care of these patients."
Cynthia Dunbar, MD, from the Hematology Branch of the National Heart, Lung and Blood Institute in Bethesda, Maryland, believes the choice of whether to take the drug or have a splenectomy ultimately belongs to the patient. "Splenectomy has a good response rate but, over time, some patients can relapse. I think it will come down to health insurance and national health programs, because these drugs are costly. You would need to be on the drug indefinitely, and we need to ask if stimulating marrow constantly for years is any good."
"What is clear in the [United States], at least, is that we see a lot of patients that are referred for treatment who don't need treatment. Judicious use of the drug is essential; we need to decide whether to do this in place of splenectomy when, in fact, splenectomy could resolve the problem," concluded Dr. Dunbar.
The study was supported by Amgen. Dr. Rummel and Dr. Bussel have disclosed no relevant financial relationships.
14th Congress of the European Hematology Association: Abstract 1059. Presented June 7, 2009.
結果顯示，服用該試驗用藥的病患只有8%接受手術，而以標準照護(SOC)治療的病患有35%進行手術(勝算比為0.17；95%信心區間[CI]為0.06 - 0.36)。另一個初級終點是治療失敗，Romiplostim組有12%病患、SOC組有27%病患(勝算比為0.37；95% CI為0.12 - 0.74)。
在該試驗中，234名病患接受Romiplostim或SOC，如cyclosporine、rituximab、azathioprine以及類固醇治療。Rummel醫師指出，SOC組有42%的病患、Romiplostim組有36%的病患接受過3次以上的ITP治療。開始時，隨機分到Romiplostim組的病患，其平均血小板數量為27 ×109/L，隨機分到SOC組者的平均血小板數量為33 × 109/L。
經過52週，每週皮下給予Romiplostim 3μg/kg ，且根據血小板數量調整劑量。治療失敗定義為，給予最高建議劑量之Romiplostim或SOC時，血小板數量20 × 109/L 以下、嚴重出血、或者因為副作用或無法耐受而改變治療。