title: Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009-2013 French PharmacoVigilance assessment.
abstract: BACKGROUND
  Romiplostim and eltrombopag, the two marketed thrombopoietin receptor agonists (TPO-RAs), have distinct binding sites and might have distinct pharmacodynamic mechanisms. The aim of this study was to compare their adverse drug reaction (ADR) patterns.
  
  
  METHODS
  We selected in the French PharmacoVigilance Database all ADRs associated with TPO-RAs from TPO-RA marketing until the 31st of December 2013. Medical charts were reviewed. We conducted disproportionality analyses comparing romiplostim exposure in the reports of a given ADR pattern (thrombosis, neurological, cutaneous, gastrointestinal or hematological) to romiplostim exposure in all other TPO-RA-related ADR reports. Reporting Odds Ratios (RORs) were adjusted for age and gender. We also compared the number of reports of a given ADR pattern per million daily defined doses (DDDs) dispensed in France during the study period.
  
  
  RESULTS
  We described 45 reports (53 ADRs) with romiplostim and 26 reports (37 ADRs) with eltrombopag. There were 19 venous thromboses. At least one other risk factor was present in 83.3% of the cases. Ten (55.6%) patients had been splenectomized previously. There were eight arterial thromboses. Another risk factor was noticed in all cases. There was no signal for an excess risk of thrombosis with romiplostim versus eltrombopag (ROR: 1.45, 95% CI [0.48-4.45]). There was a signal for a higher risk of gastrointestinal ADRs with eltrombopag (ROR: 30.28, 95% CI [3.23-383.86]) and of hematological ADRs with romiplostim (ROR: 14.36, 95% CI [1.73-119.08]). Dispensing data-adjusted comparisons led to similar results.
  
  
  CONCLUSIONS
  This study suggests different ADR patterns between romiplostim and eltrombopag.
authors.affiliation: Laboratoire de Pharmacologie Médicale et Clinique, Université Paul Sabatier, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Equipe de Pharmacoépidémiologie de l'INSERM U 1027, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France. Electronic address: guillaume.moulis@univ-tlse3.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moulis
authors.affiliation: Laboratoire de Pharmacologie Médicale et Clinique, Université Paul Sabatier, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Equipe de Pharmacoépidémiologie de l'INSERM U 1027, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: Haleh
authors.initials: H
authors.lastname: Bagheri
authors.affiliation: Equipe de Pharmacoépidémiologie de l'INSERM U 1027, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sailler
authors.affiliation: Service de Pharmacologie Clinique, Centre Régional de Pharmacovigilance, Centre Hospitalier Universitaire de Tours, 2 bd Tonnellé, 37044 Tours Cedex 9, France.
authors.forename: Annie-Pierre
authors.initials: AP
authors.lastname: Jonville-Bera
authors.affiliation: Service de Médecine Interne, Hôpital Nord, Centre Hospitalier Universitaire de Saint-Etienne, 42055 Saint-Étienne Cedex 02, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Weber
authors.affiliation: Centre Régional de Pharmacovigilance et de Renseignements sur le Médicament, Hôpital Nord, Centre Hospitalier Universitaire de Saint-Etienne, 42055 Saint-Étienne Cedex 02, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Guy
authors.affiliation: Service de Pharmacologie Clinique, Centre Régional de Pharmacovigilance de Lorraine, Centre Hospitalier Universitaire de Nancy, 29 Avenue du Maréchal-de-Lattre-de-Tassigny, 54035 Nancy Cedex, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Petitpain
authors.affiliation: Service de Pharmacologie, Toxicologie et Pharmacovigilance, Centre Régional de Pharmacovigilance, de Pharmacoépidémiologie et d'Information sur les Médicaments, Centre Hospitalier Universitaire de Limoges, 2 Avenue Martin-Luther-King, 87042 Limoges Cedex, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Laroche
authors.affiliation: Centre Régional de Pharmacovigilance, Centre Hospitalier Universitaire de Poitiers, BP 577, 86021 Poitiers Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Favrelière
authors.affiliation: Centre Régional de Pharmacovigilance, Centre Hospitalier Universitaire de Lille, 1 Place de Verdun, 59045 Lille Cedex, France.
authors.forename: Johana
authors.initials: J
authors.lastname: Béné
authors.affiliation: Centre Régional de Pharmacovigilance, Centre Hospitalier Universitaire de Nice, 4 Avenue Reine Victoria, BP 1179, 06003 Nice Cedex 1, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Baldin
authors.affiliation: Service de Médecine Interne, Clinique Adassa, 13 Place de Haguenau, 67000 Strasbourg, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Villeval-Federici
authors.affiliation: Centre Régional de Pharmacovigilance, Centre Hospitalier Universitaire de Strasbourg, 1 Place de l'Hôpital, BP 426, 67091 Strasbourg Cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Tebacher-Alt
authors.affiliation: Département de Pharmacologie Médicale et Toxicologie, Centre Régional de Pharmacovigilance de Languedoc-Roussillon, Centre Hospitalier Universitaire de Montpellier, 371 Avenue du Doyen-Gaston-Giraud, 34295 Montpellier Cedex 5, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bres
authors.affiliation: Service de Pharmacologie Clinique, UF de Pharmacovigilance, Institut de Biologie, Centre Hospitalier Universitaire de Nantes, 9 Quai Moncousu, 44093 Nantes Cedex 01, France.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Veyrac
authors.affiliation: Centre Régional de Pharmacovigilance de Bourgogne, EA 4184, Centre Hospitalier Universitaire de Dijon, 14 rue Paul-Gaffarel, BP 77908, 21079 Dijon Cedex, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Grandvuillemin
authors.affiliation: Centre Régional de Pharmacovigilance de Paris-Cochin, Assistance Publique - Hôpitaux de Paris, 27 rue du Faubourg-Saint-Jacques, 75014 Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Mauprivez
authors.affiliation: Laboratoire de Pharmacologie Médicale et Clinique, Université Paul Sabatier, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Equipe de Pharmacoépidémiologie de l'INSERM U 1027, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lapeyre-Mestre
authors.affiliation: Laboratoire de Pharmacologie Médicale et Clinique, Université Paul Sabatier, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Equipe de Pharmacoépidémiologie de l'INSERM U 1027, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France; Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Faculté de Médecine, 37 Allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
mesh_terms: D000368:Aged; D001565:Benzoates / Q000009:adverse effects*; D005260:Female; D005602:France; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D011720:Pyrazoles / Q000009:adverse effects*; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects*; D013926:Thrombopoietin / Q000009:adverse effects*
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag
keywords: Adverse drug reaction; Disproportionality analysis; Eltrombopag; Pharmacovigilance; Romiplostim; Thrombopoietin receptor agonist