ORLANDO -- Two of the largest studies ever done in chronic immune thrombocytopenia (ITP) continue to show efficacy and safety for two recently approved drugs, according to research presented at the annual meeting here of the American Society of Hematology.
An open-label extension study of romiplostim (Nplate) showed no new safety issues, no increase in adverse events over time, and stability in both dose and efficacy, according to David Kuter, MD, of Massachusetts General Hospital in Boston.
A similar extension analysis of eltrombopag (Promacta) also demonstrated continued efficacy in increasing platelet counts and reducing bleeding, while showing no new safety signals, according to Mansoor Saleh, MD, of Georgia Cancer Specialists in Atlanta.
Both drugs target the thrombopoietin receptor and were approved in 2008 to treat immune thrombocytopenia. Romiplostim is administered subcutaneously once a week, while eltrombopag is given as a daily pill, subject to some dietary restrictions.
The romiplostim extension study began in August 2004 and closed in January 2010, enrolling a total of 292 patients over that time. When the trial closed, some patients had had up to 277 weeks of exposure to the drug, Kuter said.
The primary goal of the study was to assess long-term safety of romiplostim, but the researchers also analyzed response to the drug, the use of concomitant medications for ITP, and how the dose of the drug changed over time.
- 98% of patients reported at least one adverse event, but only 35% reported a treatment-related event and only 8% experienced a serious event related to the treatment.
- There were 16 deaths on the trial, including two -- caused by a heart attack and unstable angina -- that were considered to be related to the drug.
- There were 25 thromboembolic events, including seven thought to be related to the study drug. But there was no association with any particular platelet count and the events occurred with a wide variety of exposure durations.
- Of patients receiving concurrent ITP medication at baseline, 81% were able to discontinue or reduce their dose by more than 25%.
- The median of the average weekly dose of all patients was 4 mcg/kg, and after 12 weeks of therapy doses remained relatively constant, with 78% of patients getting within 2 mcg/kg of their most frequent dose at least 90% of the time.
Out of the 292 patients enrolled in the study, 91 discontinued. That figure includes 15 deaths and 25 withdrawals of consent; in addition, 11 patients withdrew due to adverse events, and another 11 withdrew to try an alternative therapy.
The eltrombopag study -- dubbed EXTEND -- included 299 patients who had taken part in a previous study of the drug, either in the placebo or study drug arm, Saleh said. The primary goal was to analyze long-term efficacy and safety; the study is still under way although 41% have withdrawn, mainly due to adverse events (11%), patient choice (11%), and lack of efficacy (10%).
The researchers found:
- 88% of patients reached a platelet count of at least 50,000 per microliter of plasma, regardless of baseline count, use of concomitant medications at baseline, or whether they had undergone a splenectomy.
- Platelet counts rose sharply in the first two weeks of treatment and then plateaued after four weeks.
- Within four weeks, bleeding scores dropped by 50%, and after that there was very little clinically relevant bleeding.
- 37% of patients stopped at least one concomitant medication.
- There were 21 thromboembolic events in 16 patients, similar to what is seen in untreated people with the condition. As with romiplostim, there was no association with platelet count.
- There was no indication of myelofibrosis associated either with dose or duration of therapy.
- 10% patients met at least one criterion for drug-induced liver injury, but the symptoms were mild, reversible, and were not associated with symptoms of liver damage.
The studies are the largest ever done in immune thrombocytopenia but don't give much guidance as to which drug to choose, according to Terry Gernsheimer, MD, of the University of Washington in Seattle, who was not part of the research but who was one of the moderators of the session at which the studies were presented.
The bottom line, she told MedPage Today, is that the difference between them will come down to patient preference.
"These are extremely active agents," Gernsheimer said, "and they appear to be relatively safe," with the important effect of allowing many patients to come off steroid therapy.
But their clinical use, she said, will probably depend on whether patients prefer a once-weekly injection or a daily pill that has to be taken at odd hours to meet dietary restrictions.
The studies seem small compared with those seen in some other disorders, but they're large enough to avoid any concerns that they lack statistical power, according to Bethan Psaila, MD, PhD, of Imperial College London. Psaila was not part of the studies but was the other moderator of the session at which they were presented.
The numbers are a reflection of the fact that many people with immune thrombocytopenia do well without therapy, so that severe cases are relatively rare, she told MedPage Today.