Utfallsdata inom hemofili. Erik Berntorp Lunds universitet Klinisk koagulationsforskning, Malmö

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1 Utfallsdata inom hemofili Erik Berntorp Lunds universitet Klinisk koagulationsforskning, Malmö

2 Vad är hemofili? Recessiv, X-kromosomalt nedärvd åkomma som i princip endast drabbar män Brist/avsaknad av koagulationsfaktor VIII (hemofili A 80%) eller IX (hemofili B 20%) Incidens ca 1/5000 födda pojkar. I Sverige finns ca 1000 fall varav 350 med svår form Stort antal mutationer Svårighetsgrad anges som % faktornivå i blodet jmf med normalbefolkningen Svår <1 %; moderat 1-5 %; mild >5-<40 %

3 Hemofili Igår Idag Imorgon Pictures from Dept of Coag Disorders, Malmö with permission, and from Kulturen Lund

4 Osooli & Berntorp JIM 2016

5 Average Joint Physical-Examination Score Det tar ett antal år innan skillnad mellan behandlingsmetoder visar sig Prophylaxis Episodic Therapy 0 Manco-Johnson et al. NEJM 2007;357: N=25 N=25 N=29 N=33 N=27 N=29 N=26 N=27 N=22 N=25 N=22 N= Age (Yr)

6 Journal of Internal Medicine 1992; 232: Twenty-Five Years Experience of Prophylactic Treatment in Severe Haemophilia A and B Inga Marie Nilsson I.M. NILSSON, E. BERNTORP, T. LÖFQVIST * & H. PETTERSSON From the Department of Coagulation Disorders and the * Department of Orthopaedics, University of Lund, Malmö General Hospital, Malmö, and the Department of Radiology, University Hospital, Lund, Sweden

7 Assessment A Prerequisite for Developing Prophylaxis

8 The Pettersson X-Ray Score was Endorsed by WFH in 1982 Clin Orthop Relat Res Jun;(149): A Radiologic Classification of Hemophilic Arthropathy. Holger Pettersson Pettersson H, Ahlberg A, Nilsson IM. 8

9 Hemophilia Joint Health Score World Federation of Hemophilia Haemophilia Sep; 12(5): Semin Hematol Jul;30(3 Suppl 2):3-6. Hemophilia Joint Health Score Reliability Study. Prophylaxis: Musculoskeletal Evaluation. Gilbert MS. Department of Orthopedics, Mount Sinai School of Medicine, New York, NY. Berlin. Heidelberg: Springer-Verlag. 1985: Hilliard P, Funk S, Zourikian N, Bergstrom BM, Bradley CS, McLimont M, Manco-Johnson M, Petrini P, van den Berg M, Feldman BM. Department of Rehabilitation Service, the Division of Rheumatology, The Hospital for Sick Children, University of Toronto, Canada. Diagnostic Imaging in Hemophilia; Musculoskeletal and Other Hemorrhagic Complications. Petterson H, Gilbert M. 9

10 Assessment of prophylaxis in hemophilia: Important for optimized cost effectiveness ABR Physical score HJHS Imaging score Pettersson score MRI score Ultrasound Functional score Quality of life Health-economy Pharmacokinetics Survival studies Population PK/Bayesian analysis Computerized dose simulations Years/decades of follow-up needed Berntorp E. Haemophilia 2013;19:163 5.

11 Idag viktigaste utfallsdata ABR (årligt antal blödningar) Ledstatus (HJHS) Ultraljudbedömning under snabb utveckling Faktorkonsumtion QoL Hälsoekonomiskt utfall

12 Registries Web-based registries now available With time more and more countries will join these Patients will become better known and available for Education Diagnostic procedures treatment

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14 Osooli & Berntorp JIM 2016

15 Några exempel på vad som uppnåtts med register och utfallsdata inom hemofili

16 Total number of surgical procedures On Demand n=61 Prophylaxis n=95 Arthrodeses Prostheses 63 7 Synovectomies 25 2 Miscellaneous minor surgeries including tooth extractions Port implantations/extractions 16 Total number of procedures Number of procedures divided by group size Steen Carlsson et al Haemophilia 2003

17 Individualized prophylaxis: potential for cost savings while maintaining efficacy Direct comparison between two prophylaxis regimens (Dutch intermediate-dose and Swedish high-dose ) in patients with severe hemophilia born Dutch intermediate dose : Small increase in annual bleed rate (median 1.3 vs 0; p <0.01) Small increase in bleeds over 5 years (median 10 vs 2.5; p <0.01) Slightly more limitations in daily activities (median HJHS 9.0 vs 7.0 points / 144; p=0.01) Swedish high dose: Median costs per patient over 5 years were 73% higher Group level: Incremental benefits of high-dose prophylaxis appear to be limited Fischer K et al. Blood 2013 (doi: /blood ). Patient level: Prophylaxis should be tailored individually

18 Percent Alive Percent Alive Before Replacement Treatment Early Period of Replacement Treatment 100 Current Survival for Severe Haemophilia Malmö /UK Age Age Severe no factor Severe Men UK excl HIV Malmö Malmö excl HIV Men 2009 Osooli et al Haemophilia 2017 Darby et al 2007

19 Kaplan Meier Joint Survival Estimate Kaplan Meier Joint Survival Estimate 1.00 First Joint Undergo Surgery Born p=0.017 Born Born < Age Second Joint Undergo Surgery Born 1980+; born p=0.214 Born < Age Osooli et al Haemophilia 2017

20 Proportion With a Joint Score of Zero When to Start: The Swedish Experience yrs P= yrs 3-5 yrs Age at First Joint Score Conclusion: Prophylaxis should be started in the first years of life, before age 3. Astermark et al. Br J Haematol.1999;105:

21 Register måste utvecklas ytterligare Myndighetskrav Krav från behandlare Krav från patienter Krav från industri

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24 Sammanfattning Hemofili är en sällsynt sjukdom Nationellt och globalt samarbete Centralsiering Många års uppföljning nödvändigt för att se behandlingseffekter/skillnader Långtidsuppföljning av nyckelparametrar på stora material helt nödvändig Sådan har tidigare bara funnits vid få centra (Malmö, Utrecht bla) Svenskt nationellt register nu börjat etableras (äntligen!) Ett måste för att se vad den kostsamma svenska hemofilivården ger patienterna och samhället Man måste veta för att kunna se ("Man sieht nur, was man weiß Goethe)

25 The Ultimate Prophylaxis