JOINT DISEASE AND ITS MEDICAL AND SOCIO-ECONOMIC IMPACT ON HEMOPHILIA CARE IN ROMANIA
Hemophilia is a congenital, hereditary, rare bleeding disorder, which fortunately has nowadays an optimal therapeutical solution, namely a life-long replacement therapy (RT) with the missing coagulation factor VIII (hemophilia A) or IX (hemophilia B). Inappropriate treatment results in secondary morbidity, dominated by the chronic hem arthropathy, with high medical and socioeconomic burden. Objectives: As in our country, RT has been started only in 1997 and a real prophylactic replacement (PR) only in 2016/2017, we aimed at conducting a study of persons mainly with prophylactic RT and of those mainly with on-demand (OD) regimen for obtaining a comparative evaluation of the medical and socio-economic outcomes. Material and methods: This observational cross-sectional patient-reported outcome (PRO) survey included 122 patients with a severe form of the disease, willing to answer to a large questionnaire with 56 items focused on 4 domains: socio-demographic, medical, quality of health and life, and direct costs of care. Results: There have been assessed striking, statistically different results, concerning the markers which reveal clinical severity (annualized joint and non-joint bleeding rate, target joints, hem arthropathy), the need for chronic analgesic therapy and orthopedic interventions, frequency of deficiency, disability, handicap and social assistance in the group of persons with OD treatment vs. PR. The high costs related to surgical interventions and occurrence of inhibitors have been underlined, related to a secondary morbidity of hemophilia. Conclusions: The favorable effects of PR are evident also in our country; its high costs are counterbalanced by the deleterious health and quality of life results of OD treatment, and also by its high costs for the specific secondary morbidity, pleading in the favor of PR, in accordance with the principles of care in Europe.
2. Oldenburg J, Dolan G, Lemm G. Hemophilia care then, now and in the future. Hemophilia 2009; 15(1): 2-7.
3. Giangrande P, Seitz R, Behr-Gross ME, et al. European consensus proposals for treatment of hemo-philia with coagulation factors concentrates. Hemophilia 2014; 20: 322-325.
4. K Knobe. Hemophilia and joint disease: pathophysiology, evaluation and management. J. of comorbidity 2011; 1: 51-59.
5. O’Mahony B, Noone D, Giangrande P, Prihodova L. Hemophilia care in Europe - a survey of 35 countries. Hemophilia 2013; 19(4): 239-247.
6. Mondorf W, Kalnins W, Klamroth R. Patient reported outcome of 182 adults with severe hemophilia in Germany comparing prophylaxis vs. on demand replacement therapy. Hemophilia 2013; 19(4): 558-563.
7. Mannuccio Mannucci P. Hemophilia therapy: the future has begun. Hemophilia 2020; 105(3): 545-553.
8. Makris M. A golden age for Hemophilia treatment? Hemophilia 2018; 24(2): 175-176.
9. Gringeri A, Lundin B, Von Mackensen S, Mantovani L, Mannucci PM and The ESPRIT GROUP. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J of Thromb and Haemost, 2011; 9(4): 700-710.
10. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus Episodic Treatment to Pre-vent Joint Disease in Boys with Severe Hemophilia. The New England Journal of Medicine 2007; 357(6): 535-544.
11. Valentino LA, Rusen L, Elezovic I, et al. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in hemophilia B sub-jects. Hemophilia, 2014; 20(3): 398-406.
12. Manco-Johnson MJ, Kempton CL, Reding MT, et al. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J of Thrombosis and Haemostasis 2013; 11(6): 1119-1127.
13. Fischer K, Steen Carlsson K, Petrini P, Rolf Jung. Intermediate dose versus high dose prophylaxis for severe hemophilia comparing outcome and costs since the 1970. Blood 2013; 122(7): 1129-1135.
14. Yao W, Xiao J, Cheng X, et al. The Efficacy of Recombinant FVIII Low-Dose Prophylaxis in Chinese Pediatric Patients with Severe Hemophilia A: A Retrospective Analysis from the ReCARE Study. Clin Appl Thromb Hemost 2017; 23(7): 851-858.
15. Tagliaferri A, Feola G, Molinari Ac, Santoro C, Coppola and POTTER study group. Benefits of prophylaxis versus OD treatment in adolescents and adults with severe hemophilia A the POTTER study. Thromb Haemost 2015; 114(1), 35-45.
16. Noone D, O’Mahony B, Prihodova I. A survey of the outcome of prophylaxis, on-demand or com-bined treatment in 20-35-year-old men with severe hemophilia in four European countries. Hemophilia 2011; 17(5): 842-843.
17. Feldmann BM, Pai M, Rivald GE, et al. Prophylaxis Study group “Tailored prophylaxis in severe hemophilia A” interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis study. J Thromb Haemost 2006; 4(6): 1228-1236.
18. Jackson S, Ming Yang, Lenard Mimik, et al. Prophylaxis in older Canadian adults with hemophilia A: lessons and more questions. Haematology 2015; 15(4) / doi: 10.1186/s12878-015-0022-8.
19. Steen Carlsson K, Hojgard S, Glomstein A, et al. On-demand vs. prophylactic treatment for severe hemophilia in Norway and Sweden: differences in treatment characteristics and outcome. Hemophilia 2003; 9: 555-566.
20. Manco-Johnson MJ, Sanders J, Ewing N, Rodriguez N, Tarantino M, Humphries T, TEEN/TWEN Study Group. Consequences of switching from prophylaxis to on demand treatment in late teens and early adults with severe hemophilia A, the TEEN/ TWEN study. Hemophilia 2013; 19(5), 725-735.
21. Serban M, Poenaru D, Patrascu J, et al. Current trend of invasive interventions for people with he-mophilia in Romania. Haemostaseology 2019; 39(4): 377-382.
22. Serban M, Mihailov D, Poenaru D, Patrascu J. Development of inhibitors in hemophilia. Haemo-staseologie 2011; 31(1): 320-323.
23. Schramm W, Gringeri A, Ljung R, Berger K. Hemophilia care in Europe: the ESCHOL study. Hemo-philia, 2012; 18(5): 729-737.
24. Farrugia A, Cassars J, Kimber MC, et al. Treatment for life for severe hemophilia A -A cost utility model for prophylaxis vs. on treatment. Hemophilia 2013; 19(4): 228-238.
25. Farrugia A, Cassar J, Kimber MC. Treatment for life. Prophylaxis in Hemophilia A is more cost-effective than on-demand therapy in a cost-utility model. http://www.pptaglobal.org/images/ presenta-tions/11Treat.pdf.
Once an article is accepted for publication, MSJ requests a transfer of copyrights for published articles.
COPYRIGHT TRANSFER FORM FOR
REVISTA MEDICO-CHIRURGICALĂ A SOCIETĂȚII DE MEDICI ȘI NATURALIȘTI DIN IAȘI /
THE MEDICAL-SURGICAL JOURNAL OF THE SOCIETY OF PHYSICIANS AND NATURALISTS FROM IASI
We, the undersigned authors of the manuscript entitled
warrant that this manuscript, which is submitted for publication in the REVISTA MEDICO-CHIRURGICALĂ, has not been published and it is not under consideration for publication in another journal.
- we give the consent for publication in the REVISTA MEDICO-CHIRURGICALĂ, in printed and electronic format and we transfer unconditioned and complete the copyright of this manuscript to the REVISTA MEDICO-CHIRURGICALĂ, in the event of its acceptance.
- the manuscript does not break the intellectual property rights of any other person.
- we have read the submitted version of the manuscript and we are fully responsible for the content.
Names and signatures of authors / copyright owners (the following sequence is the authorship of the article):
N.B. All the authors must sign this form