Summary
First generation thrombopoietic growth factors (rhTPO and PEG-rHuMGDF), investigated
in the early 2000s, proved effective in increasing platelet count in normal volunteers,
in thrombocytopenia due to chemotherapy and also in a few cases of immune thrombocytopenic
purpura (ITP). These agents did not complete their clinical development since one
of them induced antibodies in the recipients that cross reacted with endogenous thrombopoietin
(TPO), thus causing thrombocytopenia. This promoted the ingenious design of a new
generation of thrombopoietic growth factors having no sequence homology with natural
TPO. The two main agents are romiplostim, a peptibody already approved for clinical
use in USA and eltrombopag, a non-peptide, orally active small molecule. In open label
and placebo-controlled trials both agents proved to predictably increase platelet
count in normal volunteers and in patients with ITP. With appropriate dosages (1–10
µg/kg weekly sub cutaneously for romiplostim; 50–75 mg/die per os for eltrombopag
) a platelet increase becomes significant after 7–10 days and peaks between 10–14
days. By dis -continuing treatment, platelet count returns to baseline level in 10–15
days. The response rate with both agents is above 70–80%, also in patients that had
undergone several lines of treatment, or that have failed splenectomy. The response
is maintained during the treatment, but is almost invariably lost even after several
months of successful administration. Due to the lack of a curative potential and to
the incomplete knowledge of long-term side effects, the place of these new drugs in
the management of ITP is still unsettled and their use is best restricted to refractory
patients or in preparation of splenectomy. It seems however that a new paradigm in
the treatment of ITP has been established where the focus is not on reducing platelet
consumption but on increasing platelet production.
Keywords
Immune thrombocytopenia - thrombopoietin receptor agonist - therapy
