Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009–2013 French PharmacoVigilance assessment

• The risk of gastrointestinal ADRs seems higher with eltrombopag.
• The risk of hematological ADRs seems higher with romiplostim.
• The risk of thrombosis between the two TPO-RAs seems similar.
• Another risk factor was present in four-fifths of the cases.

BackgroundRomiplostim 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.MethodsWe 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.ResultsWe 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.ConclusionsThis study suggests different ADR patterns between romiplostim and eltrombopag.