The Evaluation Of Safety And Efficacy Of Romiplostim And Placebo In The Treatment Of Adult ITP

BackgroundPrimary immune thrombocytopenia(ITP)is an acquired autoimmune disease with clinical manifestations of varying degrees of thrombocytopenia with or without cutaneous mucosal bleeding.ITP is the most common cause of clinical thrombocytopenia,accounting to about 1/3 of the total number of bleeding disorders.The current consensus is that ITP is an immune-mediated thrombocytopenia due to autoantibody-mediated platelet damage caused by excessive destruction of mononuclear macrophage system.Studies have also shown that platelet production is reduced in patients with ITP.Thrombopoietin(TPO)is a major regulator of platelet production.Romiplostim is a human TPO mimetic peptide that competes with endogenous TPO to bind to the TPO receptor on the surface of megakaryocytes and activate its endogenous pathway to promote megakaryocyte platelet production.A series of clinical studies have shown that Romiplostim can significantly increase platelet counts with good safety and effectiveness.Romiplostim became a new treatment option for ITP patients after the US Food and Drug Administration(FDA)first approved it for adult chronic ITP treatment in 2008.Objective1.To evaluate the efficacy of injectable romiplostim and placebo for the treatment of persistent or chronic ITP in adults.2.To evaluate the safety and efficacy of romiplostim at the 21st week of continuous administration.MethodThe enrolled subjects were?18-year-old adults with chronic or persistent ITP with platelet counts?30×10~9/L during the screening period.Subjects were randomized,double-blindwithRomiplostim(KyowaFermentationKirin Pharmaceutical Co.,Ltd.Products)and placebo(Romiplostim mimetic for injection:placebo without Romiplostim active ingredient)by 3:1.The starting dose was1?g/kg.w.During the treatment period,the blood routine was rechecked weekly.The dosage was adjusted from 1?g/kg to 10?g/kg according to the platelet count to maintain the platelet count at 50-200×109/L.If the platelet count is less than50×10~9/L,the dosage will be increased by 1?g/kg;if the platelet count maintaine at50-200×10~9/L,the dosage will not be changed;if the platelet count maintaine at200-400×10~9/L,the dosage will be decreased by 1?g/kg;if the platelet count>400×10~9/L,treatment will be discontinued until platelet count<50×10~9/L,and then re-administered from 1?g/kg.After 9 weeks of blinding,all subjects were treated with romimistin until the 21-week trial cycle was completed.Efficacy and safety evaluations were performed at the 7th and 21st week respectively.The evaluation criteria were based on expert consensus.Results1.After 6 weeks of treatment,the average platelet count in the romimistin group was 51.75(0-132)×10~9/L.Among them,4 cases were CR(20%),9 cases were R(45%),and 7 cases were NR(35%).The total effective rate was 65%.The average number of peripheral platelet counts in the placebo group was 14(1-32)×10~9/L,and platelet counts were no more than 50×10~9/L in all patients.All patients were NR(100%)in 5 patients.There was a significant difference in the effective rate and peripheral platelet count between the two groups(P<0.05).2.After 21 weeks of treatment with romimissetin,the average platelet count in peripheral blood was 63(0-132)×10~9/L with a total efficiency of 74%.Among them,4(21%)cases were CR,10(53%)cases were R,and 5(26%)cases were NR.3.Drug-related adverse events(AE)were dizziness(50%),muscle aches(25%),fatigue(25%),pruritus(15%),joint pain(10%),etc.The above AE were mild to moderate,and could be improved after symptomatic treatment or self-recovered within a short time.Bone marrow biopsy MF staining was 0-2 in 10 cases(40%),ITP deteriorated in 2 cases,and there was no thromboembolic event.ConclusionRomiplostim is a new option in management of persistent or chronic ITP in adults with high response rate,rapid effect,considerable tolerability,and slight adverse effects.