-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and increased risk of bleeding.
It accounts for about 30% of bleeding diseases and seriously endangers human health
.
The pathogenesis of ITP is complex and heterogeneous, and a single target is difficult to cover.
Observational studies have shown that the effectiveness of combination therapy is better than single-agent therapy
.
On November 13-14, 2021, the "2021 Coagulation Disease Summit Forum" will be held in Tianjin
.
At the meeting, Professor Ming Hou from Qilu Hospital of Shandong University gave a report on "New Exploration of ITP Combination Therapy" and introduced the exploration and progress of ITP combination therapy in recent years from "First-line Combination Therapy Program" and "Second-line Combination Therapy Program".
, Xiaobian organizes the main content as follows for readers
.
First-line combined treatment strategy 1.
A prospective study of high-dose dexamethasone (HD-DXM) combined with recombinant human thrombopoietin (rhTPO) compared with HD-DXM in the treatment of initial ITP by Professor Ming Hou’s team of DXM+rhTPO/TPO-RA The results of a sexual, multi-center, open randomized controlled clinical study were published in American Journal of Hematology in 2020.
The experimental group of this study was oral DXM 40mg/d for 4 consecutive days, and at the same time subcutaneous injection of rhTPO 300U/kg/d.
For 14 consecutive days, the control group received oral DXM 40 mg/d for 4 consecutive days
.
The results show that the initial treatment and long-term efficacy of the combined therapy are significantly better than that of single-agent therapy.
The 6-month continuous effective rate is 51%, which is significantly higher than 36.
5% of the single-agent group, and the 1-year continuous effective rate is 46%, which is also significant It was higher than 31.
2% in the single-drug group
.
And there is no statistical difference between the two groups in terms of safety
.
Professor Ming Hou said here that some basic studies have found that rhTPO or TPO receptor agonist (TPO-RA) not only promotes the proliferation and differentiation of megakaryocytes, but also has a certain immunomodulatory effect, which can improve sustained remission by inducing immune tolerance.
Therefore, short-term (14 days) use can achieve long-term relief in some patients
.
Professor Ming Hou said that this program is suitable for new-onset and severe ITP patients
.
In addition, two foreign studies using DXM and TPO-RA in the first-line treatment of ITP also achieved excellent effects of continuous remission for 6 months
.
2.
DXM+RTX About ten years ago, Italian researchers led a prospective, multi-center, open randomized controlled clinical study to compare HD-DXM combined with rituximab (RTX) and HD-DXM treatments For the curative effect of initial ITP treatment, 49 patients were enrolled in the DXM+RTX group, and 52 patients were enrolled in the DXM group.
RTX 375mg/m2 was given on 28 days, and the control group was given DXM 40mg/d on days 1-4
.
The results showed that at 6 months, the incidence of platelet counts >50×109/L, >100×109/L, and >150×109/L in the combination treatment group and the single-agent group were 63% vs 36% (P =0.
004), 53% vs 33% (P=0.
019), 43% vs 25% (P=0.
029), indicating that the efficacy of combination therapy is significantly better than that of single agent
.
In terms of safety, no adverse events (AEs) above grade 4 occurred, and there was no significant difference between the two groups of serious AEs, grade 3-4 AEs, and grade 3-4 AEs related to the study drug
.
In another randomized controlled study conducted by German researchers comparing HD-DXM combined with RTX and HD-DXM in the treatment of newly-treated ITP, 63 patients were enrolled in the DXM+RTX group and 74 patients were enrolled in the DXM group.
The results also proved The continuous effective rate of the combined treatment group for 6 months (58% vs 37%, P=0.
02) and 12 months (53% vs 33%, P<0.
05) was higher than that of the single agent group, and the duration of remission (DOR) It was also significantly higher than the single-drug group
.
Professor Ming Hou said that DXM combined with RTX treatment for newly treated ITP patients can achieve a higher remission rate without significantly increasing the incidence of AEs
.
3.
DXM+Oseltamivir In April this year, the team of Professor Ming Hou published a prospective, multi-center, open randomized control of HD-DXM combined with oseltamivir in the treatment of initial ITP in Lancet Haematology.
Clinical research results
.
Regarding why it should be combined with oseltamivir, Professor Ming Hou said that oseltamivir is an influenza virus neuraminidase inhibitor.
The results of a retrospective survey in the Netherlands showed that oseltamivir is used for treatment After prevention and prevention of influenza A, the platelet counts of patients were significantly increased, and the results of previous preclinical studies have shown that oseltamivir can induce platelet reactions in the treatment of ITP
.
However, its clinical application prospects in patients with ITP are currently unclear
.
Therefore, the team of Professor Ming Hou conducted the study to explore the efficacy of DXM combined with oseltamivir in the first-line treatment of ITP
.
The results showed that the combined treatment group had a higher 14-day initial remission rate (86% vs 66%, P=0.
030) and a higher 6-month sustained remission rate (53% vs 30%, P=0.
032) than the single-agent group.
, And the risk of bleeding was significantly reduced in the combined treatment group at 6 months
.
The adverse reactions were mild and short-lived, and there was no significant difference between the two groups
.
4.
DXM+ATRA Recently, the team of Professor Zhang Xiaohui from the Institute of Hematology, Peking University People’s Hospital conducted a prospective, multi-center, open randomized HD-DXM combined with all-trans retinoic acid (ATRA) versus HD-DXM in the treatment of initial ITP The results of the controlled clinical study were published on Lancet Haematology
.
Regarding the mechanism of ATRA to improve ITP, Professor Ming Hou said that ATRA can balance the polarization of macrophages, reduce the phagocytic destruction of platelets, and improve the hematopoietic microenvironment; secondly, ATRA has an immunomodulatory effect and can improve the number and function of regulatory T cells.
.
The results of the study showed that the 6-month sustained remission rate in the combined treatment group was significantly higher than that in the single-agent group (68% vs 41%, p=0.
0017)
.
In terms of safety, adverse reactions were mild, and there was no significant difference between the two groups
.
5.
DXM+MMF In September this year, the results of a prospective, multi-center, open randomized controlled clinical study of HD-DXM combined with mycophenolate mofetil (MMF) compared with HD-DXM in the treatment of newly-treated ITP conducted by British researchers were announced In the New England Journal, the results showed that the long-term efficacy of combination therapy was significantly better than that of monotherapy.
There was no significant difference in the initial response between the two groups.
There were no significant differences in adverse reactions, bleeding time, rescue treatment and hospitalization rates.
The combination therapy reduced the risk of recurrence and also May reduce the quality of life
.
Second-line combination therapy strategy 1.
In the exploration of the second-line treatment of ITP with RTX+rhTPO, Professor Ming Hou’s team published in Blood in 2015 the multi-center, prospective, randomized RTX combined with rhTPO versus RTX for hormone-ineffective or recurrent ITP Compared with the results of the clinical study, the results of the study showed that compared with the single-agent group, the combined treatment group significantly increased the complete remission (CR) rate (45.
4% vs 23.
7%, P=0.
026), and significantly shortened the time to remission (TTR; 7d vs.
28d, P=0.
004), but there was no significant difference in long-term efficacy between the two groups
.
And there was no significant difference in adverse reactions between the two groups
.
It shows that RTX combined with rhTPO can achieve rapid and sustained efficacy, and the long-term efficacy difference needs to be further confirmed by a larger randomized controlled study
.
2.
RTX+ATRA In addition, in October this year, Professor Zhang Xiaohui’s team once again published a major article on Blood, exploring the efficacy of low-dose RTX (LD-RTX) combined with ATRA and LD-RTX monotherapy for hormone resistance/relapsed ITP
.
A total of 168 patients with hormone resistance/relapsed ITP over 18 years old were enrolled in this study.
They were divided into two groups according to the ratio of 2:1: receiving ATRA (20mg/m2qd, oral for 12 weeks) + LD-RTX (100mg/week, continuous intravenous Infusion for 4 weeks) or LD-RTX alone
.
The main endpoint is the 1-year total remission rate (platelet count ≥30×109/L, at least two times apart [at least 7 days apart], and ≥2 times the baseline platelet count, no bleeding symptoms, no rescue treatment required)
.
The results showed that the 1-year total remission rate of the combined treatment group was significantly higher than that of the single-agent group (80% vs 59%); the 6-month sustained remission rate was also significantly higher than that of the single-agent group (61% vs 41%)
.
The most common adverse reactions in the combination treatment group were dry skin and headache/dizziness
.
It shows that ATRA combined with LD-RTX provides a promising combination treatment plan for hormone resistant/relapsed ITP patients, which can improve the overall remission rate and the sustained remission rate
.
In conclusion, Professor Ming Hou said that the combination therapy of ITP should choose drugs with different mechanisms and different side effects for multi-target combination therapy, and multi-target combination therapy is expected to change the treatment model of ITP in the future
.
Professor Ming Hou Taishan Scholar, Second-level Professor of Shandong University, Doctoral Supervisor, Director of Tumor Center, Qilu Hospital of Shandong University, Director of Department of Hematology, Director of Shandong Provincial Key Laboratory of Blood Immunity, Member of ITP International Working Group Guideline Development Expert Group Member, ASH Senior Member, APSTH Executive Committee Member of the Standing Committee of the Chinese Society of Hematology, Member of the Standing Committee of the Chinese Society of Pathophysiology of Experimental Hematology, and Vice President of the Chinese Society of Hematologists
It accounts for about 30% of bleeding diseases and seriously endangers human health
.
The pathogenesis of ITP is complex and heterogeneous, and a single target is difficult to cover.
Observational studies have shown that the effectiveness of combination therapy is better than single-agent therapy
.
On November 13-14, 2021, the "2021 Coagulation Disease Summit Forum" will be held in Tianjin
.
At the meeting, Professor Ming Hou from Qilu Hospital of Shandong University gave a report on "New Exploration of ITP Combination Therapy" and introduced the exploration and progress of ITP combination therapy in recent years from "First-line Combination Therapy Program" and "Second-line Combination Therapy Program".
, Xiaobian organizes the main content as follows for readers
.
First-line combined treatment strategy 1.
A prospective study of high-dose dexamethasone (HD-DXM) combined with recombinant human thrombopoietin (rhTPO) compared with HD-DXM in the treatment of initial ITP by Professor Ming Hou’s team of DXM+rhTPO/TPO-RA The results of a sexual, multi-center, open randomized controlled clinical study were published in American Journal of Hematology in 2020.
The experimental group of this study was oral DXM 40mg/d for 4 consecutive days, and at the same time subcutaneous injection of rhTPO 300U/kg/d.
For 14 consecutive days, the control group received oral DXM 40 mg/d for 4 consecutive days
.
The results show that the initial treatment and long-term efficacy of the combined therapy are significantly better than that of single-agent therapy.
The 6-month continuous effective rate is 51%, which is significantly higher than 36.
5% of the single-agent group, and the 1-year continuous effective rate is 46%, which is also significant It was higher than 31.
2% in the single-drug group
.
And there is no statistical difference between the two groups in terms of safety
.
Professor Ming Hou said here that some basic studies have found that rhTPO or TPO receptor agonist (TPO-RA) not only promotes the proliferation and differentiation of megakaryocytes, but also has a certain immunomodulatory effect, which can improve sustained remission by inducing immune tolerance.
Therefore, short-term (14 days) use can achieve long-term relief in some patients
.
Professor Ming Hou said that this program is suitable for new-onset and severe ITP patients
.
In addition, two foreign studies using DXM and TPO-RA in the first-line treatment of ITP also achieved excellent effects of continuous remission for 6 months
.
2.
DXM+RTX About ten years ago, Italian researchers led a prospective, multi-center, open randomized controlled clinical study to compare HD-DXM combined with rituximab (RTX) and HD-DXM treatments For the curative effect of initial ITP treatment, 49 patients were enrolled in the DXM+RTX group, and 52 patients were enrolled in the DXM group.
RTX 375mg/m2 was given on 28 days, and the control group was given DXM 40mg/d on days 1-4
.
The results showed that at 6 months, the incidence of platelet counts >50×109/L, >100×109/L, and >150×109/L in the combination treatment group and the single-agent group were 63% vs 36% (P =0.
004), 53% vs 33% (P=0.
019), 43% vs 25% (P=0.
029), indicating that the efficacy of combination therapy is significantly better than that of single agent
.
In terms of safety, no adverse events (AEs) above grade 4 occurred, and there was no significant difference between the two groups of serious AEs, grade 3-4 AEs, and grade 3-4 AEs related to the study drug
.
In another randomized controlled study conducted by German researchers comparing HD-DXM combined with RTX and HD-DXM in the treatment of newly-treated ITP, 63 patients were enrolled in the DXM+RTX group and 74 patients were enrolled in the DXM group.
The results also proved The continuous effective rate of the combined treatment group for 6 months (58% vs 37%, P=0.
02) and 12 months (53% vs 33%, P<0.
05) was higher than that of the single agent group, and the duration of remission (DOR) It was also significantly higher than the single-drug group
.
Professor Ming Hou said that DXM combined with RTX treatment for newly treated ITP patients can achieve a higher remission rate without significantly increasing the incidence of AEs
.
3.
DXM+Oseltamivir In April this year, the team of Professor Ming Hou published a prospective, multi-center, open randomized control of HD-DXM combined with oseltamivir in the treatment of initial ITP in Lancet Haematology.
Clinical research results
.
Regarding why it should be combined with oseltamivir, Professor Ming Hou said that oseltamivir is an influenza virus neuraminidase inhibitor.
The results of a retrospective survey in the Netherlands showed that oseltamivir is used for treatment After prevention and prevention of influenza A, the platelet counts of patients were significantly increased, and the results of previous preclinical studies have shown that oseltamivir can induce platelet reactions in the treatment of ITP
.
However, its clinical application prospects in patients with ITP are currently unclear
.
Therefore, the team of Professor Ming Hou conducted the study to explore the efficacy of DXM combined with oseltamivir in the first-line treatment of ITP
.
The results showed that the combined treatment group had a higher 14-day initial remission rate (86% vs 66%, P=0.
030) and a higher 6-month sustained remission rate (53% vs 30%, P=0.
032) than the single-agent group.
, And the risk of bleeding was significantly reduced in the combined treatment group at 6 months
.
The adverse reactions were mild and short-lived, and there was no significant difference between the two groups
.
4.
DXM+ATRA Recently, the team of Professor Zhang Xiaohui from the Institute of Hematology, Peking University People’s Hospital conducted a prospective, multi-center, open randomized HD-DXM combined with all-trans retinoic acid (ATRA) versus HD-DXM in the treatment of initial ITP The results of the controlled clinical study were published on Lancet Haematology
.
Regarding the mechanism of ATRA to improve ITP, Professor Ming Hou said that ATRA can balance the polarization of macrophages, reduce the phagocytic destruction of platelets, and improve the hematopoietic microenvironment; secondly, ATRA has an immunomodulatory effect and can improve the number and function of regulatory T cells.
.
The results of the study showed that the 6-month sustained remission rate in the combined treatment group was significantly higher than that in the single-agent group (68% vs 41%, p=0.
0017)
.
In terms of safety, adverse reactions were mild, and there was no significant difference between the two groups
.
5.
DXM+MMF In September this year, the results of a prospective, multi-center, open randomized controlled clinical study of HD-DXM combined with mycophenolate mofetil (MMF) compared with HD-DXM in the treatment of newly-treated ITP conducted by British researchers were announced In the New England Journal, the results showed that the long-term efficacy of combination therapy was significantly better than that of monotherapy.
There was no significant difference in the initial response between the two groups.
There were no significant differences in adverse reactions, bleeding time, rescue treatment and hospitalization rates.
The combination therapy reduced the risk of recurrence and also May reduce the quality of life
.
Second-line combination therapy strategy 1.
In the exploration of the second-line treatment of ITP with RTX+rhTPO, Professor Ming Hou’s team published in Blood in 2015 the multi-center, prospective, randomized RTX combined with rhTPO versus RTX for hormone-ineffective or recurrent ITP Compared with the results of the clinical study, the results of the study showed that compared with the single-agent group, the combined treatment group significantly increased the complete remission (CR) rate (45.
4% vs 23.
7%, P=0.
026), and significantly shortened the time to remission (TTR; 7d vs.
28d, P=0.
004), but there was no significant difference in long-term efficacy between the two groups
.
And there was no significant difference in adverse reactions between the two groups
.
It shows that RTX combined with rhTPO can achieve rapid and sustained efficacy, and the long-term efficacy difference needs to be further confirmed by a larger randomized controlled study
.
2.
RTX+ATRA In addition, in October this year, Professor Zhang Xiaohui’s team once again published a major article on Blood, exploring the efficacy of low-dose RTX (LD-RTX) combined with ATRA and LD-RTX monotherapy for hormone resistance/relapsed ITP
.
A total of 168 patients with hormone resistance/relapsed ITP over 18 years old were enrolled in this study.
They were divided into two groups according to the ratio of 2:1: receiving ATRA (20mg/m2qd, oral for 12 weeks) + LD-RTX (100mg/week, continuous intravenous Infusion for 4 weeks) or LD-RTX alone
.
The main endpoint is the 1-year total remission rate (platelet count ≥30×109/L, at least two times apart [at least 7 days apart], and ≥2 times the baseline platelet count, no bleeding symptoms, no rescue treatment required)
.
The results showed that the 1-year total remission rate of the combined treatment group was significantly higher than that of the single-agent group (80% vs 59%); the 6-month sustained remission rate was also significantly higher than that of the single-agent group (61% vs 41%)
.
The most common adverse reactions in the combination treatment group were dry skin and headache/dizziness
.
It shows that ATRA combined with LD-RTX provides a promising combination treatment plan for hormone resistant/relapsed ITP patients, which can improve the overall remission rate and the sustained remission rate
.
In conclusion, Professor Ming Hou said that the combination therapy of ITP should choose drugs with different mechanisms and different side effects for multi-target combination therapy, and multi-target combination therapy is expected to change the treatment model of ITP in the future
.
Professor Ming Hou Taishan Scholar, Second-level Professor of Shandong University, Doctoral Supervisor, Director of Tumor Center, Qilu Hospital of Shandong University, Director of Department of Hematology, Director of Shandong Provincial Key Laboratory of Blood Immunity, Member of ITP International Working Group Guideline Development Expert Group Member, ASH Senior Member, APSTH Executive Committee Member of the Standing Committee of the Chinese Society of Hematology, Member of the Standing Committee of the Chinese Society of Pathophysiology of Experimental Hematology, and Vice President of the Chinese Society of Hematologists
