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On July 21, 2018, Novartis announced that Eltrombopag (trade name Revolade), the first and only non-peptide oral thrombopoietin receptor agonist (TPO-RA) approved, is available in China. Indications are chronic primary immune thrombocytopenic Purpura (Immunologic Thrombocytopenic Purpura, hereinafter referred to as ITP) after splenectomy.
Eltrombopag, as the first generation of TPO-RA, was recommended by the 2019 ASH guidelines as the preferred regimen for second-line ITP treatment[1]. It not only quickly increases the number of platelets, but also uses a convenient oral method. In the past, the drug of rising platelets was mainly injected, and the listing of edlopipa subverted the traditional route of administration, and its oral administration method greatly improved the patient's medication compliance and created a new era of patient comfort treatment.
What is ITP – the platelet killer around us
Chronic immune (idiopathic) thrombocytopenic purpura (ITP), also known as immune or autoimmune thrombocytopenia, is an autoimmune blood disorder characterized by a low platelet count lasting more than 6 months and accompanied by bleeding from the mucous membranes of the skin. Symptoms range from mild abrasions and mucosal bleeding to bleeding anywhere in the body, with intracranial hemorrhage being the most severe. Studies have shown that there are 236 adult cases per million population [2]. However, the pathogenesis of ITP is not fully understood, and it is currently believed that pathogenic antiplatelet autoantibodies and T cell-mediated platelet destruction and damage to megakaryocyte function are the main pathogenic mechanisms.
The current dilemma of treating ITP
The goal of treatment with ITP is to increase the platelet count, thereby reducing the risk of severe bleeding. The underlying cause of ITP is thought to be rapid platelet destruction, so treatment options focus on slowing platelet destruction by inhibiting platelet autoantibody production or inhibiting macrophage-mediated platelet destruction. Treatment options include glucocorticoids (e.g., prednisone), intravenous immunoglobulins, splenectomy, and the use of immunomodulators such as danazol or azathioprine in the treatment of refractory disease. These treatments are not always effective or can only produce short-lived effects, and treatment-related adverse events tend to limit further use.
Impaired thrombocytopenia may also be a potential pathogenesis of ITP [3]. Therefore, medical scientists have also studied the stimulating effects of growth factors and growth factor analogues on megakaryocyte production, such as recombinant thrombopoietin growth factor. Although these drugs increase platelet counts, some drugs (e.g., polyethylene glycolated recombinant human megakaryocyte growth and development factor, recombinant thrombopoietin) are associated with autoantibodies that cross-react with endogenous thromboplastin and neutralize endogenous thrombopoietin, resulting in severe thrombocytopenia. As a result, researchers began developing other drugs, such as TPO-RA, which can activate thrombopoietin receptors in different sites to produce thrombopoietin.
Treat the itP's breakers – Atropopa
So, is there a drug that treats ITP that can improve the rapid elevation of platelets and reduce the risk of treatment, but also improve the quality of life and comfort of patients? Edrepopa is available in China, bringing new treatment options to ITP patients. As the first and only approved oral small molecule, non-peptide TPO-RA, edlopapaz can not only quickly improve platelets, but also be easy to take, greatly improving patient medication compliance.
Edrepopa selectively binds to the transmembrane domain of platelet, megakaryocytes, and giant nucleus cell precursor cell surface thrombopoietin receptors and functions through the Janus kinase/signal transducer and transcriptional activator (JAK/STAT) signaling pathways. Therefore, edrepopa has a positive effect on the proliferation and differentiation of bone marrow progenitor megakaryocytes.
Advantages of Edlopapa Therapy ITP
(1) It can stimulate and maintain the function of hematopoietic stem cells, and reduce the inhibitory effect of interferon (IFN).
(2) Improve individual immune tolerance in patients with aplastic anemia, inhibit macrophage activity and dendritic cell maturation, and increase the number of regulatory B cells and T cells.
(3) It can effectively regulate the immune system of patients with aplastic anemia, reduce the release of IFN and tumor necrosis factor (TNF), and increase the release of transforming growth factor (TGF).
(4) It has the effect of iron removal ions, which can reduce intracellular iron overload.
(5) Edrepopa has an affirmative effect in the treatment of thrombocytopenia. Novartis announced that a long-term clinical trial called "EXTEND" showed that edopopapia showed long-term safety and efficacy in treating adult ITP, and the results of the study were published online in Blood [4].
Indications and contraindications of edlopapa
Indications:
(1) Adults and children over one year of age ITP patients, especially those who have a poor response to corticosteroids, immunoglobulins and splenectomy.
(2) Thrombocytopenia in patients with chronic hepatitis C can be combined with interferon.
(3) Severe aplastic anemia.
contraindication:
(1) Patients with myelodysplastic syndrome (MDS).
(2) Patients who are allergic to eklopipa.
Usage and dosage of edlopipa
The recommended starting dose is 25 mg / day for patients with general ITP and the maximum dose is 75 mg / day. For patients with chronic ITP who do not respond well to corticosteroids, immunoglobulins, or splenectomy, the recommended starting dose is 50 mg/day and the maximum dose is 75 mg/day. When the platelet count reaches and is maintained at 50,000/ml, the dose is adjusted gradually, and if the platelet count does not increase to a level that can avoid clinically important bleeding after 4 weeks of maximum dose, the drug should be discontinued.
Estrepopa should be taken on an empty stomach (1 hour before or 2 hours after a meal) and more than 4 hours apart from drugs, foods, or supplements containing polyvalent cations (e.g., calcium, iron).
Liver function should be closely monitored during the administration of edlopipra, and patients with moderate or severe hepatic insufficiency should start with a dose of 25 mg / day. If the ALT level rises to 3 times the upper limit of normal or continues to rise for 4 weeks, or is accompanied by a direct increase in bilirubin, or with liver damage, liver decompensation, the drug should be discontinued.
The price of Edupoppa and how to obtain it
In July 2018, Atropopa was approved for marketing by the State Food and Drug Administration (CFDA). In terms of price, novartis group's original research drugs are priced at about 5890 yuan per box, and the drug specification is 25mg *28 tablets. Taken according to the recommended dose, the initial dose for most patients is 25 mg / day, and the economic burden of monthly treatment is heavier. In addition to the original research drug, Edlopapa also has a Bengal version of the generic drug, which is cheaper and has the same effect as the original research drug. Patients in need can be consulted and obtained through regular overseas medical institutions (such as medical companion travel).
Outlook and outlook
In the latest edition of the National Medical Insurance Catalogue released in 2019, Edupopapi was successfully included in medical insurance, which is conducive to the drug entering more hospitals, meeting the medical needs of more patients, and providing patients with affordable high-quality drugs. Professor Hu Yu of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology said that as a recommended drug for ITP second-line treatment, its listing in China will enhance the effect of domestic ITP treatment. It is believed that in the near future, through the negotiation of the National Medical Insurance Bureau, the price of Edupopapia will be further reduced, which will bring good news to more patients!