Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP).
BACKGROUND
Romiplostim is a peptibody protein that raises platelet counts during long-term treatment of patients with chronic immune thrombocytopenia (ITP). Clinical outcomes related to increased platelet counts include a reduced risk of bleeding and a potential risk of thrombosis.


OBJECTIVE
To evaluate bleeding and thrombotic events occurring in chronic ITP patients during two phase 3, randomized, placebo-controlled, 24-week studies of romiplostim and during subsequent treatment in an open-label extension study.


METHODS
In the phase 3 trials, 125 patients were randomized to romiplostim or placebo; romiplostim dose was adjusted to maintain platelet counts of 50-200 x 10(9) L(-1). Patients who completed the phase 3 trials could enroll in the extension study in which all patients received romiplostim.


RESULTS
In the phase 3 trials, a significantly greater percentage of patients treated with placebo (34%) had bleeding adverse events of moderate or greater severity than did patients treated with romiplostim (15%, P = 0.018). In the extension study, the incidence of bleeding adverse events of moderate or greater severity decreased from 23% of patients in the first 24 weeks to 12% after 24-48 weeks, remaining < or = 6% thereafter. The exposure-adjusted incidence of thrombotic events was 0.1 per 100 patient-weeks in the phase 3 studies, and 0.08 per 100 patient-weeks in the extension study where patients received romiplostim for up to 144 additional weeks.


CONCLUSIONS
The incidence and severity of bleeding was decreased in chronic ITP patients treated with romiplostim compared with placebo, and the incidence of thrombotic events was not different between the two groups.
Gernsheimer
T B
TB
Puget Sound Blood Center, 1100 Fairview Avenue North, LM-200, Seattle, WA 98109, USA. bldbuddy@u.washington.edu
George
J N
JN
Aledort
L M
LM
Tarantino
M D
MD
Sunkara
U
U
Matthew Guo
D
D
Nichol
J L
JL
D002908:Chronic Disease; D004311:Double-Blind Method; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D010919:Placebos; D011446:Prospective Studies; D011961:Receptors, Fc / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000503:physiopathology; D013926:Thrombopoietin / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000139:chemically induced*
D010919:Placebos; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim