Rusotinib tablettes (ruxolitinib / Jakafi) pour le traitement de la fibrose médullaire à risque modéré ou élevé, y compris la fibrose médullaire primitive, la myélofibrose après polyglobulie primitive et la myélofibrose après thrombocytose idiopathique. Les patients présentant une fibrose de la moelle osseuse à risque modéré ou élevé se réfèrent aux patients de plus de 65 ans ou qui présentent l'une des affections suivantes: anémie, symptômes physiques, diminution du nombre de globules blancs, diminution du nombre de cellules embryonnaires ou diminution du nombre de plaquettes. 80% à 90% des cas.
Rusotinib tablets (ruxolitinib / Jakafi) are currently marketed in the United States, Europe and other places, but are still not marketed in mainland China. Rusolitinib is the first Janus associated kinase (JAK) inhibitor approved in the world so far, and the first specific myelofibrosis treatment drug approved by the FDA and the world. Rusotinib is available in 5 doses of 5, 10, 15, 20, and 25 mg / tablet, and is administered as an oral regimen twice a day. Bone marrow fibrosis is a progressive and potentially life-threatening rare blood system disease, which is a myeloproliferative tumor and is estimated to affect 1.60-18.5 million people in the United States. Bone marrow fibrosis patients are gradually replaced by scar tissue, so that blood cell production has to be carried out in organs such as liver and spleen. Anemia, leukopenia, and thrombocytopenia occur. Patients with bone marrow fibrosis are characterized by bone marrow failure and splenomegaly, as well as fatigue, musculoskeletal pain, abdominal discomfort, severe itching, night sweating, and satiety, which seriously impair the quality of life. Splenomegaly and systemic symptoms in patients with myelofibrosis are associated with JAK pathway signaling dysfunction. Rusotinib is an oral JAK1 and JAK2 inhibitor, and JAK1 and JAK2 are involved in the regulation of blood and immune function.
FDA The decision to approve the above lusotinib was mainly based on data from two phase III randomized, double-blind, and controlled clinical trials with two codenames, COMFORT-I and COMPORT-Ⅱ. The COMFORT-I study included a total of 309 patients with uncomfortable or resistant allogeneic bone marrow transplantation, or relapsed primary bone marrow fibrosis, myelofibrosis after polycythemia and idiopathic thrombocythemia, and the results showed The proportion of patients who achieved the primary end point after 24 weeks of treatment with lusotinib or placebo, even if the spleen volume decreased by ≥35%, was 41.9% and O. respectively. 7% (P <0.000 1). In addition, the proportion of patients with an improvement of ≥50% in the improved Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS) in the two groups of lusotinib or placebo was 45.9% and 5.3% (P <0.001), and the median time to response was less than 4 weeks. The C0MPORT-11 study included 219 patients with uncomfortable or allogeneic bone marrow transplantation, or relapsed primary bone marrow fibrosis, myelofibrosis after polycythemia and idiopathic thrombocytosis, and the results showed that The proportion of patients with sotinib or the best therapy hydroxyurea (hydroxyurea) or glucocorticoid after 48 weeks of treatment to reduce the spleen volume ≥35% was 28.5% and 0 (P <0.001). Les effets indésirables hématologiques les plus courants du traitement par le lusotinib observés dans C0MPORT — I et COMPORT-11 étaient la thrombopénie et l'anémie liées à la dose, mais ces deux effets indésirables sont faciles à gérer et poussent rarement les patients à arrêter le traitement; les effets secondaires non sanguins les plus courants sont la diarrhée, les étourdissements, les maux de tête, la fatigue et les nausées.
