Signal for Thrombosis with Eltrombopag and Romiplostim: A Disproportionality Analysis of Spontaneous Reports Within VigiBase®.
BACKGROUND
Eltrombopag and romiplostim are thrombopoietin receptor agonists (TPO-RAs) marketed for immune thrombocytopenia (ITP). Thrombotic events have been reported with both drugs. This study was aimed at assessing whether there is a signal for differential risks of thrombosis between these two TPO-RAs.


METHODS
We carried out a disproportionality analysis in the World Health Organization global individual case safety report (ICSR) database (VigiBase(®)). We selected all ICSRs with exposure to a TPO-RA between January 2011 and December 2014. We searched for exposures to eltrombopag or romiplostim in thrombosis reports as compared with other ICSRs, and we calculated adjusted reporting odds ratios (aRORs).


RESULTS
We identified 5850 ICSRs, including 764 cases of thrombosis. In multivariate analyses, there was a signal for an increased risk of thrombosis (venous or arterial; aROR 1.72, 95 % confidence interval [CI] 1.47-2.02), venous thrombosis (aROR 1.88, 95 % CI 1.53-2.31), arterial thrombosis (aROR 1.54, 95 % CI 1.18-2.00), ischaemic stroke (aROR 1.65, 95 % CI 1.13-2.42) and myocardial infarction (aROR 1.50, 95 % CI 1.05-2.13) with eltrombopag as compared with romiplostim. Restriction to ICSRs reported by physicians led to similar results. However, worldwide dispensing data for romiplostim and eltrombopag were not accessible, so the rates of thrombosis with both drugs were not normalized by the daily defined doses and the generalizability of the results is limited.


CONCLUSIONS
This study suggests the presence of a signal for an increased risk of thrombosis with eltrombopag compared with romiplostim. These results must be confirmed and quantified by large aetiological pharmacoepidemiological studies.
INSERM, UMR 1027, Toulouse, France.|Université de Toulouse III, UMR 1027, Toulouse, France.
Thi-Thanh Loan
TT
Nguyen
INSERM, UMR 1027, Toulouse, France.|Université de Toulouse III, UMR 1027, Toulouse, France.
Aurore
A
Palmaro
INSERM, UMR 1027, Toulouse, France.|Université de Toulouse III, UMR 1027, Toulouse, France.|Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.|Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Pharmacopole Midi-Pyrénées, Toulouse, France.
François
F
Montastruc
INSERM, UMR 1027, Toulouse, France.|Université de Toulouse III, UMR 1027, Toulouse, France.|Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Maryse
M
Lapeyre-Mestre
INSERM, UMR 1027, Toulouse, France. guillaume.moulis@univ-tlse3.fr.|Université de Toulouse III, UMR 1027, Toulouse, France. guillaume.moulis@univ-tlse3.fr.|Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, Toulouse, France. guillaume.moulis@univ-tlse3.fr.
Guillaume
G
Moulis
D016907:Adverse Drug Reaction Reporting Systems; D000375:Aging; D001565:Benzoates / Q000009:adverse effects*; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects*; D009203:Myocardial Infarction / Q000139:chemically induced; D011720:Pyrazoles / Q000009:adverse effects*; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects*; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced; D013926:Thrombopoietin / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced* / Q000401:mortality
D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag