The treatment of immune thrombocytopenia (ITP)—focus on thrombopoietin receptor agonists

Exacerbation of immune thrombocytopenia following COVID‐19 vaccination

“…Since ITP is a disorder of both increased platelet destruction as well as impaired platelet production, 10 the rapid exacerbation of thrombocytopenia by vaccination might occur by either mechanism. Vaccines prepared from dead bacteria or viruses are potent stimulators to the immune system in general and many adjuvants (for example aluminium salts, DNA and lipids) are commonly added to other vaccines to enhance the immune system 11–13 .…”

Chemically modified in-vitro-transcribed mRNA encoding thrombopoietin stimulates thrombopoiesis in mice

“…Since TPO affects nearly all stages of thrombopoiesis to stimulate the proliferation and maturation of megakaryocytes and subsequent platelet production, TPO and its receptor have been the main focus for the development of pharmacological treatment for thrombocytopenia. 36 The development of recombinant human TPO (rhTPO) and pegylated rhTPO (PEG-rhTPO) has been halted because anti-TPO antibodies have been shown to develop in healthy individuals; these can cross-react with endogenous TPO to induce thrombocytopenia. 7 Second-generation TPO-RAs romiplostim and eltrombopag have been demonstrated to be highly effective 10,37 ; however, there are several major concerns regarding the use of TPO-RAs in patients with ITP, including the risk of bone marrow fibrosis, rebound thrombocytopenia when TPO-RA is abruptly stopped, and increased thrombosis in patients with underlying hypercoagulable statuses.…”

Novel therapies for immune thrombocytopenia

“…While current therapies such as TPO‐RA may have long‐term response rates of over 80% 6 with eventual treatment‐free remissions in at least half of all patients, 7,8 some patients fail these therapies, have adverse responses to treatment, or lack access to these treatments. There remains an unmet medical need for new treatments of ITP in both the early stages of disease, 9 i.e.…”

“…Of the four current TPO receptor agonists, three have been approved by multiple regulatory agencies for treating ITP (romiplostim, eltrombopag, avatrombopag) and the fourth (lusutrombopag) only for patients with chronic liver disease undergoing procedures. 6,131,132 A fourth non-peptide TPO receptor agonist, hetrombopag olamine, is currently under development in China for several indications and was approved in China for second-line treatment of ITP on 16 June 2021. 133 Its structure and function are similar to those of eltrombopag (Fig 4).…”

“…For example, prednisone has been long thought to reduce platelet destruction 5 but platelet kinetic studies have suggested that it mainly increases the rate of platelet production. 4 While current therapies such as TPO-RA may have longterm response rates of over 80% 6 with eventual treatmentfree remissions in at least half of all patients, 7,8 some patients fail these therapies, have adverse responses to treatment, or lack access to these treatments. There remains an unmet medical need for new treatments of ITP in both the early stages of disease, 9 i.e.…”