6. The University of Western Australia
Structure and function of human albumin
人血白蛋白的结构及功能
Digestive and Liver Disease Volume 48, Issue 1, January 2016, Pages 4-15
消化与肝脏疾病,第48卷,第1版,2016年1月,第4-15页
VOLUME
REPLACEMENT
– TRAUMA,
SHOCK
容量置换-用于创
伤、休克
SEPSIS 脓毒症
LIVER DISEASE 肝病
…………………..
8. The University of Western Australia
Why colloids in sepsis?
为什么在治疗脓毒症时使用胶体?
Possible effects of albumin on the disturbed
microcirculatory effects of sepsis
白蛋白对脓毒症破坏的微循环作用的潜在影响
Albumin decreases neutrophil activation induced by fluid infusion, crystalloids and
synthetic colloids increase it. Rhee P, et al. Crit Care Med 2000; 28(1): 74-78.
白蛋白减弱了由输液引起的中性粒细胞活化作用,而晶体和合成胶体增强了该作
用。Rhee P等人。重症监护医学,2000; 28(1): 74-78。
Albumin reduces TNF induced endothelial activation. Nohe et al Intensive Care Med
1999; 25: 1381-1385; Zhang et al Cardiovasc Res. 2002 Sep;55(4):820-9
白蛋白减弱了TNF诱发的内皮细胞活化。 Nohe 等人。“重症监护医学”,1999;
25: 1381-1385;张等人,“心血管研究”,2002年9月;55(4):820-9
Albumin solution reverses the LPS induced albumin leakage across vessel walls. Powers
KA, et al. Crit Care Med 2003; 31: 2355-63 ;Anning PB et Intensive Care Med. 2004
Oct;30(10):1944-9
白蛋白溶液逆转了LPS诱发的白蛋白穿过血管壁的渗漏。 Powers KA等人。“重症
监护医学”,2003; 2355-63; Anning PB 等人,“重症监护医学”,2004年10月;
30(10):1944-9
Albumin infusion results in sustained thiol levels in septic patients. Quinlan G, et al. Clin
Sci 1998; 95: 459-65.
白蛋白输注导致脓毒症患者持续保持一定的硫醇水平。 Quinlan G等人,“临床科
学”,1998; 95:459-65。
Spronk et al Critical Care 2004, 8:462-468
9. The University of Western Australia
ROC curve analyses for albumin levels on predicting hospital mortality and Multiple organ
dysfunction syndrome (MODS) incidence in surgical sepsis.
关于预测外科脓毒症患者住院死亡率及多器官衰竭症状发生率的白蛋白水平ROC曲线分析
Sun et al. (2015), Risk factors and prognosis of hypoalbuminemia in surgical septic patients. PeerJ 3:e1267 DOI 10.7717/peerj.126
孙等人(2015)。外科脓毒症患者低蛋白血症的风险因素及预后, PeerJ 3:e1267 DOI 10.7717/peerj.126
P<0.001 P<0.001
10. The University of Western Australia
Survival curves of 3 large studies of volume resuscitation with
human albumin solutions in severe sepsis
利用严重脓毒症患者人血白蛋白溶液进行的三大研究的生存曲线
SAFE EARSS ALBIOS
Journal of Critical Care Volume 35, October 2016, Pages 161-167
重症监护杂志,第35卷,2016年10月,第161-167页
11. Fluid Therapy输液疗法
• We recommend crystalloids as the fluid of choice for initial resuscitation
and subsequent intravascular volume replacement in patients with sepsis
and septic shock
• 我们建议将晶体溶液作为脓毒症和感染性休克患者初始复苏和后继血
管内容量置换的首选。
(Strong recommendation, moderate quality of evidence).
(强烈建议,中等水平的证据)。
• We suggest using albumin in addition to crystalloids when patients
require substantial amounts of crystalloids
• 我们建议当患者需要摄入大量的晶体溶液时,除晶体溶液之外,还可
使用白蛋白。
(weak recommendation, low quality of evidence).
(非强烈建议,低水平证据)。
13. Intensive Care Med (1999) 25: 1381±1385
重症监护医学 (1999) 25: 1381±1385
Heterogeneity between albumin products
白蛋白制品间的异质性
Klammt et al Zeitschrift für Gastroenterologie 2001;39
Suppl 2():24-7
Klammt等人,消化内科杂志,2001;39 Suppl 2():24-7
Binding site II for diazepam
安定结合位点II
Expression of endothelial cell adhesion molecules
内皮细胞粘附分子的表达
15. Prevalence of Haemophilia A
甲型血友病的患病率
Effect of FVIII usage
使用凝血因子VIII的作用
FVIII IU/capita
人均凝血因子VIII量
(单位:IU)
Survival from
worse effects
从较坏影响中生存
下来
Adequate episodic therapy
充分的发作性疗法
Joint surgery
关节手术
Secondary prophylaxis in children
Primary prophylaxis with
current protocols
根据现行协议开展的一级预防
Tolerization
耐受
Increased prophylaxis dosage
预防剂量加大
Prophylaxis throughout life
终生预防
16. Growth of Factor VIII in Units over the past 30 years
过去30年来凝血因子VIII的增长
16
0
2,000
4,000
6,000
8,000
10,000
12,000
14,000
1988 1990 1992 1994 1996 1998 2000 2003 2005 2008 2010 2012 2014 2016
IU(M) Worldwide FVIII units sold
全球范围内出售的凝血因子VIII数量 2000-2016 CAGR
2000-2016年的年均复合增长率
rFVIII: 10.9%
pdFVIII: 4.3%
Total FVIII: 7.9%
FVIII总计:7.9%
Recombinant Factor VIII
重组凝血因子VIII
Plasma-derived Factor VIII
血浆凝血因子VIII
17. Impact of inhibitors on hemophilia A mortality in the United States
抑制剂对美国甲型血友病患者死亡率的影响
Soucie et al Am. J. Hematol. 90:400–405, 2015
Soucie等人,Am. J. Hematol。90:400–405,2015
18. Clinical data
The most controversal risk factor for the development of inhibitors in hemophilia patients depends on the type of the therapeutic molecule used, plasma-derived concentrates or recombinant rFVIII
在血友病患者抑制剂开发中,最具争议的风险因素取决于所用治疗分子、血浆浓缩物或重组FVIII的类型。
- Plasma-derived products may vary in purity and VWF content
- 血浆制品的纯度和VWF含量会有所不同
- Recombinant products produced in mammalian tissue culture are of high purity and do not contain VWF
- 在哺乳动物组织培养液中产生的重组产物纯度高,且不含VWF
Type of FVIII concentrates
凝血因子VIII浓缩物的分类
19. Patients treated with plasma-derived factor
VIII containing von Willebrand factor had a
lower incidence of inhibitors than those treated
with recombinant factor VIII.
对于接受含有von Willebrand凝血因子的血
浆凝血因子VIII治疗的患者,抑制剂的发生
率要低于使用重组凝血因子VIII治疗的患
者。
. N Engl J Med 2016;374:2054-2064
J Med Econ. 2018
Apr 21:1-16
医药经济杂志,
2018年4月,
21:1-16
20. SIPPET – Therapeutic Progression
SIPPET-治疗进展
• The SIPPET study is the first RCT to demonstrate that the risk of inhibitor development in PUPs is nearly doubled when
using rVIII vs pdVIII/VWF.
• SIPPET研究是第一个证明当使用rVIII与pdVIII / VWF时PUP中抑制剂生长风险几乎翻倍的随机对照试验。
• Inhibitor development in patients has a catastrophic effect on patient well-being and on health care budgets.
• 患者体内抑制剂的生长对其健康和医疗预算都具有灾难性的影响。
• Minimising the risk of inhibtor through the use of pdVIIIVWF for the first 50 ED of treatment is an evidence-based
measure, reflecting the therapeutic principle of «Primum Non Nocere».
• 通过使用pdVIIIVWF治疗前50个ED可以最大限度地降低抑制剂风险。这是一项基于证据的措施,反映了“患者安
全第一”的治疗原则。
21. Hemophilia A Product Choice in the US since 2000
自2000年以来美国甲型血友病治疗药物的选择
21
*Helixate FS is no longer produced in 2018, but supplies still exist
*2018年已不再生产Helixate FS ,但该药品的供应仍在继续
Jan 2000
2000年1月
Alphanate
Koate DVI
Hemofil M
Monoclate
Recombinate
Kogenate
Helixate
Jan 2010
2010年1月
Alphanate
Koate DVI
Hemofil M
Monoclate
Recombinate
Kogenate FS
Helixate FS
Advate
Xyntha
Jan 2018
2018年1月
Alphanate
Koate DVI
Hemofil M
Monoclate
Recombinate
Kogenate FS
Helixate FS*
Advate
Xyntha
Novoeight
Eloctate
Nuwiq
Adynovate
Kovaltry
Afstyla
Hemlibra
23. IgG Increasingly Dominates
Plasma Protein Sales
免疫球蛋白(IgG)在日益
主宰血浆蛋白的销售额
35.8%
39.3%
42.9%
43.6%
45.8%
47.7%
45.6%
47.3%
2000 2003 2005 2008 2010 2012 2014 2016
IgG as a Percent of Worldwide Plasma
Product Sales (US $)
IgG在全球血浆产品销售额中所占的比例
(单位:美元)Share of IgG went from under 36% in 2000 to
almost 48% in 2016 in US dollars
IgG在蛋白质产品中所占的份额从2000年的不到
36%增至到2016年的将近48%
Average annual growth from 2000 to 2016 for IgG
was 11.0%, compared to 7.7% for all other proteins
2000年至2016年,IgG的平均年度增长率为11.0
%,而所有其他蛋白质的平均年增长率仅为7.7
%
23
24. The University of Western Australia
Mortality in Common Variable Immune deficiency
常见变异型免疫缺陷病患者的死亡率
Mortality by year since diagnosis
自诊断日期开始患者的年度死亡率
Helen Chapel et al. Blood 2008; 112:277-286
Helen Chapel等人。血液,2008;112:277-286
25. The University of Western Australia
CIDP – EBM!
CIDP-循证医学!
«The evidence from RCTs shows that IVIg improves disability for at least
two to six weeks compared with placebo, with an NNTB of three. During
this period it has similar efficacy to plasma exchange, oral prednisolone
and intravenous methylprednisolone. In one large trial, the benefit of IVIg
persisted for 24 and possibly 48 weeks. Further research is needed to
compare the long-term benefits as well as side effects of IVIg with other
treatments.”
“来自随机对照试验的证据表明,与安慰剂相比,IVIg可使至少改善障
碍2周至6周,NNTB为3。 在此期间,它具有与血浆置换、口服泼尼松龙
和静脉注射甲基强的松龙相似的功效。 在一次大型试验中,IVIg的效
果持续了24周,可能会持续48周。我们需要开展进一步的研究来比较
IVIg与其他治疗方法相比的长期效果和副作用。”
26. 26
Other Plasma Proteins with High Growth
增长较快的其他血浆蛋白
• AAT (Alpha-1 Antitrypsin)
• AAT(α-1抗胰蛋白酶)
• 2000-2016 annual growth rate of 13.7%
• 2000-2016年年度增长率:13.7%
• PCC (Prothrombin Complex Concentrate)
• PCC (凝血酶原复合浓缩物)
• 2000-2016 annual growth rate of 16.7% 2000-2016年年度增长率:16.7%
129
1000
42
500
2000 2016
Sales($M)
销售额(单位:百万美元)
AAT PCC
AAT and PCC WW Sales
AAT和PCC WW的销售额
200
1100
2010 2016
Sales($M)
销售额(单位:百万美元)
C1-INH WW Sales
C1-INH WW的销售额
• C1-INH (C1- Esterase Inhibitor)
• C1-1NH(C1-酯酶抑制剂)
• 4th most valuable plasma protein in 2016
• 2016年第四种最有价值的血浆蛋白产品
27. The University of Western Australia
Plasma Protein Therapies – Current reflections
血浆蛋白治疗 – 对当前的反思
The plasma therapeutics industry continues to grow and provide a number of important medicines.
血浆治疗行业继续发展并提供许多重要的药物。
The evidence base for the use of plasma therapies ranges from the robust to the debatable , with chronic, congentital deficiencies having
the highest level of evidence.
使用血浆疗法的循证从有力到有争议,其中,慢性、先天性缺陷的证据水平最高。
The industry’s current driver is immunoglobulin, the consumption of which continues to grow, particularly as a therapy for a number of
automimmune disorders.
该行业目前的驱动力是免疫球蛋白,其消费量在持续增长,特别是用作许多自身免疫性疾病的治疗方法。
While alternative treatments to many plasma therapies have been developed, the financial sector appears to be confident in the industry’s
medium term future.
虽然已经开发了许多血浆疗法的替代治疗方法,但金融行业似乎对该行业的中期前景很有信心。
28. The University of Western Australia
Acknowledgements
鸣谢
Thanks to Dr Matthew Hotchko and the Market Research Bureau
for data and analysis
感谢Matthew Hotchko博士和市场研究局提供的数据及分析。