1. Challenges in the treatment of hemophilia Renchi Yang, MD Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

2. Healthcare Delivery System Developed countries Emerging countries Developing countries Undeveloped countries

3. Challenges Complications: inhibitor development, viral infections (HIV, Hepatitis, etc) ； hemarthropathy/pseudotumor Aging issue Affordable? Available? Compliance

4. Adherence rate to secondary prophylaxis among patients with severe hemophilia A Ono O et al., Haemophilia 2009;15:1032–8 100％ 90％ 80％ 70％ 60％ 50％ 40％ 30％ 20％ 10％ 0％0％ 3-56-1213-1819-2930-3940-4950- yrs of age ＞＝ 50 ％ 75-51 ％ 90-76 ％＞ 90 ％

5. Obstacles against introduction of the prophylaxis by age Ono O et al., Haemophilia 2009;15:1032–8 yrs of age Total score Difficulty in venous access Risk for appearance of inhibitors Mental stress on the patient Unwillingness of family members Feeling no necessity Inadequate system for guidance Problems with drug safety Poor adherence to replacement therapy Others 250 200 150 100 50 0 ＜3＜3 3-56-1213-

6. Hemarthropathy in different age goups Zhang L, et al. Hemophilia 2003,9(6):696-702

7. Pseudotumor

8. Beijing Tianjin Hefei Jinan Guangzhou Hong Kong Shanghai CHINA Area: 9 600 000 Km 2 Population: 1.3 billion

9. ● 6 initial network ● 17 new centres Haemophilia care situation Low diagnosis rate Lack of specialised hospitals –clinical and lab expertise Complex medical insurance system Access and availbility of treatment Lack of awareness

10. Current Status of treatment Ø Low supply of plasma derived concentrates Ø High cost of concentrates Ø Low coverage and reimbursement by Insurance

11. “Planned care is more effective than random care”

12. WFH HTCCNC Secretary: Renchi Yang Vice secretary: Xuefeng Wang Tianjin Institute of Hematology Beijing PUMC Hospital Shanghai Ruijin Hospital Guangzhou Nanfang Hospital Hefei Anhui Provincial Hospital Jinan Shandong Blood center National Hemophilia Registry Center Coagulation Testing Training Center Hemophilia Nurse Training Center Physiotherapist Training Center Chinese Society of Hematology Thrombosis and Hemostasis Committee

13. Regional Hemophilia Network Beijing ： Henan, Shanxi, Gansu Qinghai, Ningxia, Xinjiang Tianjin ： Hebei, Shaanxi, Inner Mongolia Liaoning, Jilin, Helongjiang Guangzhou ： Guangxi, Hainan Yunnan, Guizhou Shanghai ： Jiangsu, Zhejiang, Fujian Sichuan, Chongqing Anhui ： Jiangxi, Hunan Hubei Shandong ： Tibet

14. HTCCNC meeting 1st HTCCNC meeting: Jinan, 2004 2nd HTCCNC meeting: Shanghai, 2005 3rd HTCCNC meeting: Hefei, 2006 4th HTCCNC meeting: Beijing, 2007 5th HTCCNC meeting: Tianjin, 2008 6th HTCCNC meeting: Guangzhou, 2009 7th HTCCNC meeting: Jinan, 2010 8th HTCCNC meeting: Wuhan, 2012

15. Evolution of Product Availability –Before 1995 ： Cryoprecipitates, FFP, plasma derived concentrates (non virus- inactivated) –1995 ： Domestic produced plasma derived concentrates (virus-inactivated) –2002 ： rhFVIIa （ NovoSeven ） –2007 ： rhFVIII （ Kogenate FS® ） –2013: Adavate, Xyntha, Benefix

16. Evolution of Medical Insurance –Before 2001 ： No national medical insurance program –2002 ： Some hemophilia patients covered by medical insurance –2003 ： FVIII concentrates / PCC covered by medical insurance in some cities (Tianjin, Beijing, Shanghai, etc.) –2005 ： FVIII concentrates covered by national medical insurance all over the country –2007 ： outpatient covered as inpatient –2008 ： rhFVIII concentrates covered by medical insurance in some cities (Guangzhou, Tianjin, etc.)

17. Electronic patient registry

18. 2010-Q4 ：各中心 电脑和打印机到位 2010-3-7 ：血友病病例信 息报送培训会 2010-4-16 ：人民网 “ 名 医大讲堂 ” 介绍国家血友 病登记系统 2010-1-12 ：百特与卫生部 签署捐赠协议 2010-4-13 ， News conference 2010-7-6, Provincial center workshop

19. Inhibitor rate in China 1435 hemophilia （ 16/3/2007-5/6/2008 ） ： 1108 severe ， 249 moderate ， 78 mild. 1363 no relation. 56/1435 （ 3.9% ） inhibitor ， 18/56 （ 32.1% ） high titer （ ≥5BU/ml ）. Severe ： 48/1108 （ 4.3% ）； Moderate ： 6/249 （ 2.4% ）； Mild ： 2/78 （ 2.5% ）。 Wang XF, et al. Haemophilia 2010, 16(4):632-9

20. Key players & contributers Organizations National Haemophilia Study Group since 1985 Haemophilia Home of China established in 2000 Haemophilia Treatment Centre Collaborative Network of China established in 2004 Development support WFH since 2001 NNHF fellowships & projects since 2006 GAP programme started in 2009 Grants by pharmaceutical companies

21. Acknowledgement Members of the HTCCNC: Dr. Xinsheng Zhang, Dr. Jing Sun, Dr. Xuefeng Wang, Dr. Jingsheng Wu, Dr. Runhui Wu, Dr. Renchi Yang and Dr. Yongqiang Zhao Consultants: Prof. Man-Chiu Poon, Calgary, CANADA, Dr. K.H. Luke, Ottawa, CANADA, Prof. Changgeng Ruan and Prof. Hongli Wang Hemophilia Patients Union of China World Federation of Hemophilia, Novo Nordisk Hemophilia Foundation Baxter, Bayer, Novo Nordisk, Pfizer Ministry of Health, PRC

22. THANKS ！ THANKS ！