Long-term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials.
OBJECTIVE
Thrombopoietin receptor agonists (TPOra) are the only treatments for immune thrombocytopenia (ITP) for which evidence of efficacy and safety from randomized, placebo-controlled trials is available. We sought to determine the long-term tolerability of the TPOra romiplostim, with a particular focus on thrombosis, bleeding, bone marrow (BM) reticulin, neoplasms/haematological malignancies and fatal events.


METHODS
Data from 13 romiplostim clinical trials in which 653 patients with ITP received romiplostim for up to 5 yr (921.5 patient-years) were pooled; subject incidence rates and exposure-adjusted event rates (per 100 patient-years) were calculated.


RESULTS
The rate of thrombotic events (6% of patients, 7.5 events per 100 patient-years) did not appear to increase over time; 9 events were associated with platelet counts >400 × 10(9) /L and 10 with romiplostim doses exceeding current recommendations. Serious and grade ≥3 bleeding each occurred in approximately 8% of patients (~11 events per 100 patient-years). Adverse events of BM reticulin were recorded for 12 patients (1.8%, 1.3 events per 100 patient-years, confirmed by bone biopsy in ten patients) and BM collagen for one patient (0.2%, 0.1 event per 100 patient-years, confirmed by trichrome staining). Neoplasms and haematological malignancies occurred in 2.1% and 0.8% of patients, respectively (2.2 and 0.7 events per 100 patient-years). Fatal events occurred in 3.7% of patients (2.6 events per 100 patient-years, four events treatment-related).


CONCLUSIONS
Romiplostim is the TPOra for which the longest duration of safety data is available. Our data demonstrate that long-term romiplostim treatment is well tolerated, with no new safety signals, even in patients treated for up to 5 yr.
San Bortolo Hospital, Vicenza, Italy.
Francesco
F
Rodeghiero
Roberto
R
Stasi
Aristoteles
A
Giagounidis
Jean-François
JF
Viallard
Bertrand
B
Godeau
Ingrid
I
Pabinger
Douglas
D
Cines
Howard
H
Liebman
Xuena
X
Wang
Paul
P
Woodard
D000328:Adult; D000368:Aged; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011961:Receptors, Fc / Q000008:administration & dosage*; D053628:Receptors, Thrombopoietin / Q000819:agonists / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D012155:Reticulin / Q000378:metabolism; D013926:Thrombopoietin / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome
D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D012155:Reticulin; D013926:Thrombopoietin; C488777:romiplostim
adverse events; immune thrombocytopenia; review; romiplostim