The thrombopoietin mimetic romiplostim produced a higher rate of platelet response, a lower incidence of treatment failure, less need for splenectomy, and less bleeding than did a variety of standard-of-care therapies in patients with immune thrombocytopenia, according to a report in the Nov. 11 issue of the New England Journal of Medicine.
At the same time, romiplostim produced fewer adverse effects than did the traditional treatments, leading to an improved quality of life, wrote Dr. David J. Kuter of Massachusetts General Hospital, Boston, and his associates.
To assess the efficacy and safety of romiplostim for immune thrombocytopenia, the investigators compared it with standard medical therapies in 234 patients treated at 85 medical centers throughout North America, Europe, and Australia. The study subjects were adults who had not undergone splenectomy and who had failed to respond to at least one traditional treatment. They were randomly assigned to receive open-label romiplostim (157 patients) or standard-of-care therapy (77 patients) for 1 year, and then followed for an additional 6-month safety monitoring period.
The study was designed and sponsored by Amgen, maker of romiplostim, and Amgen also gathered the data, conducted the statistical analyses, and interpreted the results.
Patients in both study groups were allowed to receive additional therapies, such as intravenous immune globulin or glucocorticoids, if they were deemed necessary.
The two main end points were the rate of treatment failure and the need for splenectomy, both of which were significantly better with romiplostim.
Treatment failure rates were 11% (18 of 157 subjects) with romiplostim and 30% with traditional therapies (23 of 77 subjects). Patients receiving romiplostim fared better with every component of treatment failure, including major bleeding episodes, lack of efficacy, and severe adverse effects. The time to treatment failure also was significantly longer with romiplostim.
The incidence of splenectomy was 9% (14 of 157 patients) with romiplostim and 36% (28 of 77 patients) with traditional therapies. The time to splenectomy also was "markedly prolonged" longer with romiplostim. "Avoidance of splenectomy may allow for a spontaneous remission in a substantial number of patients and may benefit those who are not surgical candidates," Dr. Kuter and his colleagues said (N. Engl. J. Med. 2010;363:1889-99).
Additional treatments were needed in significantly more subjects in the standard-of-care group (79%) than in the romiplostim group (44%).
Moreover, patients receiving romiplostim were 2.3 times more likely to show a platelet response than those in the standard-of-care group. The proportion of patients showing a platelet response ranged from 71% to 92% with romiplostim, compared with 26% to 51% with standard-of-care treatments. Also, the mean platelet count was higher with romiplostim for the entire duration of the study.
Treatment-related serious adverse events occurred in 5% of patients taking romiplostim and 8% of those taking standard-of-care therapies. Headache and fatigue were the most frequent mild adverse effects.
Adverse events considered to be "of interest" with thrombopoietin mimetics include bleeding, thrombosis, increased bone marrow reticulin, hematologic cancer, or myelodysplastic syndromes.
The rates of overall bleeding and serious bleeding both were significantly lower in the romiplostim group, and twice the proportion of patients receiving traditional therapies required transfusions (17% vs. 8%). The only hematologic cancers that developed were in the standard-of-care group. And there were no abnormal nonhematologic lab results and no neutralizing antibodies to romiplostin or thrombopoietin.
One patient in the romiplostim group showed bone marrow reticulin during the 6-month safety follow-up, but the level was within normal limits.
Both study groups showed improved quality of life after treatment, with the romiplostin group showing significantly greater benefits. However, the magnitude of this effect "is of uncertain clinical benefit," the investigators said.
"Our results show that romiplostim not only maintains platelet counts more effectively than standard medical therapies but also reduces the overall rate of treatment failure and the need for splenectomy," they noted.
This study was sponsored and designed by Amgen, which also gathered the data, conducted the statistical analyses, and interpreted the results. Dr. Kuter and his associates reported ties to numerous industry sources.