Bidirectional inefficacy or intolerability of thrombopoietin receptor agonists: new data and a concise review.
There is evidence that the thrombopoietin-receptor agonists romiplostim and eltrombopag may have different therapeutic values and adverse reaction profiles. Here we present new data and provide a review of all studies dealing with switching between these two drugs.



A total of 89 patients (38 males and 51 females, aged between 14-87 years) were treated with eltrombopag and/or romiplostim between 2007 and 2016 at our institution. Eltrombopag was switched to romiplostim or vice versa in 32 patients. In addition, all published data concerning patients treated sequentially with different thrombopoietin-receptor agonists were identified via a computer-assisted search and summarised in this article.



Thirty-two of 89 patients treated with a thrombopoietin-receptor agonist in our institution were given both eltrombopag and romiplostim sequentially. Therapy was switched to the alternate thrombopoietin-receptor agonist 36 times, due to inefficacy (n=21), adverse reactions (n=14), and a patient's preference (n=1). In addition, data from 126 patients who have been treated with both agonists have been published by other groups. In total eltrombopag was replaced by romiplostim in 56 cases due to poor or no response or to adverse reactions. Forty-five patients responded to treatment with romiplostim, 11 patients shared cross-resistance and nine had adverse reactions to romiplostim. In contrast, romiplostim was replaced by eltrombopag in 106 cases. Seventy-eight patients responded to eltrombopag, 27 shared cross-resistance and 19 had adverse reactions to eltrombopag.



Eltrombopag and romiplostim often share bidirectional cross-resistance and/or adverse reactions. Both drugs appear to cause more adverse reactions than have been previously reported.
Institute of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.|Department of Cardiology and Pneumology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany.
Fabian
F
Depré
Institute of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
Nasra
N
Aboud
Institute of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
Beate
B
Mayer
Institute of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
Abdulgabar
A
Salama
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D011961:Receptors, Fc / Q000008:administration & dosage*; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D013926:Thrombopoietin / Q000008:administration & dosage* / Q000009:adverse effects*
D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag