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Z Gastroenterol 2016; 54(08): 760-769
DOI: 10.1055/s-0042-105655
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Kosten einer leitliniengerechten Versorgung von Hepatitis-C-Patienten im Zeitalter Interferon-freier Therapien

Costs of a guideline-based treatment of patients with chronic hepatitis C in the era of interferon-free treatment
J. T. Stahmeyer
1   Institut für Epidemiologie Sozialmedizin und Gesundheitssystemforschung, Medizinische Hochschule Hannover, Germany
,
S. Rossol
2   Innere Medizin, Krankenhaus Nordwest, Frankfurt, Germany
,
F. Bert
2   Innere Medizin, Krankenhaus Nordwest, Frankfurt, Germany
,
S. Liersch
1   Institut für Epidemiologie Sozialmedizin und Gesundheitssystemforschung, Medizinische Hochschule Hannover, Germany
,
C. Krauth
1   Institut für Epidemiologie Sozialmedizin und Gesundheitssystemforschung, Medizinische Hochschule Hannover, Germany
› Author Affiliations
Further Information

Publication History

08 January 2016

23 March 2016

Publication Date:
16 August 2016 (online)

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Zusammenfassung

Die Therapie der chronischen Hepatitis-C-Infektion hat sich mit der Zulassung neuer direkt antiviral wirkender Substanzen grundlegend verändert. Sie erlauben Heilungsraten von über 90 %, weisen ein akzeptables Nebenwirkungsprofil auf und ermöglichen eine erhebliche Verkürzung der Therapiedauer. Daher empfehlen auch die aktuellen deutschen Leitlinienergänzungen ausschließlich den Einsatz dieser neuen Interferon-freien Therapien. Die Fortschritte in der Therapie wurden jedoch von einem erheblichen Anstieg der Therapiekosten begleitet, was sowohl national als auch international zu Diskussionen geführt hat. Ziel der Arbeit war die systematische Kostenanalyse für die nach aktueller Leitlinienergänzung empfohlenen Therapieregime sowie die Ableitung der durchschnittlichen Kosten pro Therapieerfolg. Die Kostenkalkulation wurde nach Genotyp, Behandlungs- (naiv/erfahren) und Zirrhosestatus des Patienten stratifiziert. Dabei erfolgte eine Unterteilung in (1.) basisdiagnostische Maßnahmen, (2.) Monitoring und (3.) Arzneimittel. Die Kostenbewertung wurde aus Perspektive der gesetzlichen Krankenversicherung vorgenommen. Für therapienaive nicht zirrhotische Genotyp-1-Patienten wurden mittlere Kosten von 41 766 €/SVR für die Therapie mit SOF/LDV ermittelt (PTV/r/OMV+DSV: 53 129 €/SVR). Für zirrhotische Patienten ergaben sich Kosten von 60 323 €/SVR (SOF/LDV+RBV) bzw. 80 604 €/SVR (PTV/r/OMV+DSV+RBV). Für therapieerfahrene nicht zirrhotische Genotyp-1-Patienten wurden Kosten von 60 366 €/SVR für SOF/LDV bzw. 53 134 €/SVR für PTV/r/OMV+DSV±RBV ermittelt (zirrhotische Patienten: 62 208 €/SVR für SOF/LDV+RBV; 80 824 €/SVR für PTV/r/OMV+DSV+RBV). Für therapienaive Genotyp 1-Patienten lagen die Kosten pro geheiltem Patienten im Bereich der bisherigen Therapien, bei therapieerfahrenen Patienten noch darunter. Für die anderen Genotypen lagen sowohl die Kosten als auch die Kosten pro SVR über denen der bisherigen Standardtherapie. Erste internationale langfristige Kosten-Effektivitäts-Analysen zeigen jedoch, dass die Therapien als kosteneffektiv angesehen werden können.

Abstract

The treatment of chronic hepatitis C has considerably changed with the introduction of recent direct acting antivirals. These antivirals have sustained virologic response (SVR) rates above 90 % as well as reduced toxicity and treatment duration. Therefore, current German guidelines recommend these interferon-free regimens as first-choice treatment. Nevertheless, recent developments were accompanied by a significant increase in treatment costs, which led to extensive discussions on reasonable pharmaceutical prices. The aim of the current study was to analyze the average treatment costs and costs per patient cured for guideline treatment recommendations. Analyses were stratified according to genotype, treatment status (naive/experienced), and presence/absence of cirrhosis. Costs were separated in (1.) basic diagnostic procedures, (2.) monitoring, and (3.) pharmaceuticals. The calculation is based on a remuneration scheme in the statutory health insurance system. In treatment-naïve non-cirrhotic patients, the average cost is 41 766 €/SVR for the treatment with SOF/LDV calculated (PTV/r/OMV+DSV: 53 129 €/SVR). In treatment-naive cirrhotic patients, costs were 60 323 €/SVR (SOF/LDV+RBV) and 80 604 €/SVR (PTV/r/OMV+DSV+RBV). Treatment-experienced genotype 1 patients had average costs of 60 366 €/SVR for SOF/LDV treatment as well as 53 134 €/SVR for PTV/r/OMV+DSV±RBV treatment (cirrhotic patients: 62 208 €/SVR for SOF/LDV+RBV; 80 824 €/SVR for PTV/r/OMV+DSV+RBV). The average treatment costs per SVR in treatment-naive genotype 1 patients are comparable to previous standard of care treatments and lower in treatment-experienced patients. In other genotypes, treatment costs and costs per cure are significantly higher compared to previous standard of care. However, long-term modelling studies show that new regimens are cost-effective.

Schlüsselwörter

Hepatitis C - Leitlinie - Kosten - Kosten pro SVR - Kosteneffektivität

Key words

hepatitis C - guideline - costs - costs per SVR - cost effectiveness
 

  • Literatur

  • 1 Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014; 61: S58-S68
    CrossrefPubMedGoogle Scholar
  • 2 Robert Koch-Institut. Hepatitis C im Jahr 2014. Epi Bull 2015; 2015: 289-302
    PubMedGoogle Scholar
  • 3 Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology 2014; 146: 1176-1192
    CrossrefPubMedGoogle Scholar
  • 4 Bruggmann P, Berg T, Ovrehus AL et al. Historical epidemiology of hepatitis C virus (HCV) in selected countries. J Viral Hepat 2014; 21: 5-33
    PubMedGoogle Scholar
  • 5 Razavi H, Waked I, Sarrazin C et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014; 21: 34-59
    PubMedGoogle Scholar
  • 6 Sarrazin C, Berg T, Ross RS et al. Prophylaxis, diagnosis and therapy of hepatitis C virus (HCV) infection: the German guidelines on the management of HCV infection. Z Gastroenterol 2010; 48: 289-351
    Google Scholar
  • 7 McCombs J, Matsuda T, Tonnu-Mihara I et al. The risk of long-term morbidity and mortality in patients with chronic hepatitis C: results from an analysis of data from a Department of Veterans Affairs Clinical Registry. JAMA Intern Med 2014; 174: 204-212
    CrossrefPubMedGoogle Scholar
  • 8 Singal AG, Volk ML, Jensen D et al. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol 2010; 8: 280-288
    CrossrefPubMedGoogle Scholar
  • 9 Camma C, Di Bona D, Schepis F et al. Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data. Hepatology 2004; 39: 333-342
    CrossrefPubMedGoogle Scholar
  • 10 van der Meer AJ, Veldt BJ, Feld JJ et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 2012; 308: 2584-2593
    CrossrefPubMedGoogle Scholar
  • 11 van der Meer AJ, Veldt BJ, Feld JJ et al. The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection. J Viral Hepat 2014; 21: 568-577
    CrossrefPubMedGoogle Scholar
  • 12 Dieperink E, Pocha C, Thuras P et al. All-cause mortality and liver-related outcomes following successful antiviral treatment for chronic hepatitis C. Dig Dis Sci 2014; 59: 872-880
    CrossrefPubMedGoogle Scholar
  • 13 Backus LI, Boothroyd DB, Phillips BR et al. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol 2011; 9: 509-516
    CrossrefPubMedGoogle Scholar
  • 14 Sarrazin C, Berg T, Cornberg M et al. Expert opinion on boceprevir- and telaprevir-based triple therapies of chronic hepatitis C. Z Gastroenterol 2012; 50: 57-72
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Sarrazin C, Berg T, Buggisch P et al. S3 guideline hepatitis C addendum. Z Gastroenterol 2015; 53: 320-334
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Stahmeyer JT, Rossol S, Bert F et al. Costs of a guideline-based treatment of patients with chronic hepatitis C in Germany. Z Gastroenterol 2014; 52: 1041-1049
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Stahmeyer JT, Rossol S, Krauth C. Outcomes, costs and cost-effectiveness of treating hepatitis C with direct acting antivirals. J Comp Eff Res 2015; 4: 267-277
    CrossrefPubMedGoogle Scholar
  • 18 Hoofnagle JH, Sherker AH. Therapy for hepatitis C--the costs of success. N Engl J Med 2014; 370: 1552-1553
    CrossrefPubMedGoogle Scholar
  • 19 Cohen J. Pharmaceuticals. Advocates protest the cost of a hepatitis C cure. Science 2013; 342: 1302-1303
    CrossrefPubMedGoogle Scholar
  • 20 Braun S, Prenzler A, Mittendorf T et al. Bewertung von Ressourcenverbräuchen im deutschen Gesundheitswesen aus Sicht der Gesetzlichen Krankenversicherung. Gesundheitswesen 2009; 71: 19-23
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 EASL. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015; 63: 199-236
    CrossrefPubMedGoogle Scholar
  • 22 AASLD. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology 2015; 62: 932-954
    CrossrefPubMedGoogle Scholar
  • 23 Gane EJ, Hyland RH, An D et al. High Efficacy of LDV/SOF Regimens for 12 Weeks for Patients With HCV Genotype 3 or 6 Infection. 65th Annual Meeting of theAmerican Association for theStudy of Liver Diseases. Boston, MA: Nov 7–11 2014, Abstract LB-11 2014
    PubMedGoogle Scholar
  • 24 Kowdley KV, Gordon SC, Reddy KR et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014; 370: 1879-1888
    CrossrefPubMedGoogle Scholar
  • 25 Gilead Sciences GmbH. Fachinformation – Harvoni® 90 mg/400 mg Filmtabletten. 2014
    PubMedGoogle Scholar
  • 26 Afdhal N, Zeuzem S, Kwo P et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370: 1889-1898
    CrossrefPubMedGoogle Scholar
  • 27 Feld JJ, Kowdley KV, Coakley E et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1594-1603
    CrossrefPubMedGoogle Scholar
  • 28 Ferenci P, Bernstein D, Lalezari J et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014; 370: 1983-1992
    CrossrefPubMedGoogle Scholar
  • 29 AbbVie Ltd. Fachinformation – Viekirax® 12,5 mg/75 mg/50 mg Filmtabletten. 2015
    PubMedGoogle Scholar
  • 30 AbbVie Ltd. Fachinformation – Exviera® 250 mg Filmtabletten. 2015
    PubMedGoogle Scholar
  • 31 Bourliere M, Sulkowski M, Omata M et al. An Integrated Safety and Efficacy Analysis of >500 Patients With Compensated Cirrhosis Treated With Ledipasvir/Sofosbuvir With or Without Ribavirin, AASLD 2014. 2014
    PubMedGoogle Scholar
  • 32 Poordad F, Hezode C, Trinh R et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014; 370: 1973-1982
    CrossrefPubMedGoogle Scholar
  • 33 Afdhal N, Reddy KR, Nelson DR et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370: 1483-1493
    CrossrefPubMedGoogle Scholar
  • 34 Zeuzem S, Jacobson IM, Baykal T et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1604-1614
    CrossrefPubMedGoogle Scholar
  • 35 Andreone P, Colombo MG, Enejosa JV et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology 2014; 147: 359-365
    CrossrefPubMedGoogle Scholar
  • 36 Zeuzem S, Dusheiko GM, Salupere R et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014; 370: 1993-2001
    CrossrefPubMedGoogle Scholar
  • 37 Lawitz E, Gane EJ. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 369: 678-679
    CrossrefPubMedGoogle Scholar
  • 38 Gilead Sciences GmbH. Fachinformation – Sovaldi® 400 mg Filmtabletten. 2014
    PubMedGoogle Scholar
  • 39 Jacobson IM, Gordon SC, Kowdley KV et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013; 368: 1867-1877
    CrossrefPubMedGoogle Scholar
  • 40 Nelson DR, Cooper JN, Lalezari JP et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015; 61: 1127-1135
    CrossrefPubMedGoogle Scholar
  • 41 Foster GR, Pianko S, Brown A et al. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology 2015; 149: 1462-1470
    CrossrefPubMedGoogle Scholar
  • 42 Hezode C, Asselah T, Reddy KR et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet 2015; 385: 2502-2509
    CrossrefPubMedGoogle Scholar
  • 43 Leroy V, Angus P, Bronowicki JP et al. Daclatasvir, Sofosbuvir, and Ribavirin for Hepatitis C Virus Genotype 3 and Advanced Liver Disease: A Randomized Phase III Study (ALLY-3+). Hepatology 2016; DOI: 10.1002/hep.28473.
    PubMedGoogle Scholar
  • 44 Curry MP, Bacon B, Dieterich D et al. Effectiveness of 8 or 12 week LDV-SOF in Treatment-Naïve Patients with Non-Cirrhotic, Genotype 1 Hepatitis C: Real-World Experience from the TRIO Network. AASLD 2015 2015;
    PubMedGoogle Scholar
  • 45 Stahmeyer JT, Krauth C, Bert F et al. Costs and outcomes of treating chronic hepatitis C patients in routine care – results from a nationwide multicenter trial. J Viral Hepat 2016; 23: 105-115
    CrossrefPubMedGoogle Scholar
  • 46 Kassenärztliche Bundesvereinigung. Rahmenvorgaben 2015: 1,8 Milliarden Euro mehr für Arzneimittel. 2014 http://www.kbv.de/html/1150_12036.php [Zugriff: 04.02.2016]
    PubMedGoogle Scholar
  • 47 Steinebrunner N, Sprinzl MF, Zimmermann T et al. Early virological response may predict treatment response in sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center “real-life” cohort. BMC Gastroenterol 2015; 15: 97
    CrossrefPubMedGoogle Scholar
  • 48 Wehmeyer MH, Jordan S, Luth S et al. Efficacy and safety of sofosbuvir-based triple therapy in hepatitis C genotype 4 infection. Dig Liver Dis 2015; 47: 811-814
    CrossrefPubMedGoogle Scholar
  • 49 Hüppe D, Wiebner B, Wedemeyer H. Das Deutsche Hepatitis C-Register: erste Daten. HepNet Journal 2015; 9: 12-13
    PubMedGoogle Scholar
  • 50 Curry MP, Bacon B, Dieterich D et al. Effectiveness of 12 or 24 week LDV-SOF and 12 week LDV-SOF + RBV in Treatment-Experienced Patients with Cirrhotic, Genotype 1 Hepatitis C: Real-world Experience from the TRIO Network. AASLD 2015 2015;
    PubMedGoogle Scholar
  • 51 Mauss S, Schewe K, Rockstroh JK et al. Sofosbuvir-based treatments for patients with hepatitis C virus (HCV) mono-infection and human immunodeficiency virus (HIV)-HCV co-infection with genotype 1and 4 in clinical practice – Results from the GErman hepatitis C COhort (GECCO). AASLD 2015 2015;
    PubMedGoogle Scholar
  • 52 Backus LI, Belperio PS, Shahoumian TA et al. Effectiveness of sofosbuvir-based regimens in genotype 1 and 2 hepatitis C virus infection in 4026 U. S. Veterans. Aliment Pharmacol Ther 2015; 42: 559-573
    CrossrefPubMedGoogle Scholar
  • 53 Dieterich D, Bacon B, Flamm S et al. Final evaluation of 955 HCV patients treated with 12 week regimens containing sofosbuvir +/- simeprevir in the TRIO network: Academic and community treatment of a real-world, heterogeneous population. Gastroenterology 2015; 148: S1001
    PubMedGoogle Scholar
  • 54 Gissel C, Gotz G, Mahlich J et al. Cost-effectiveness of Interferon-free therapy for Hepatitis C in Germany – an application of the efficiency frontier approach. BMC Infect Dis 2015; 15: 297
    CrossrefPubMedGoogle Scholar
  • 55 Stahmeyer JT, Rossol S, Bert F et al. P0817: Cost-effectiveness of treating chronic hepatitis C genotype-1 with Ledipasvir and Sofosburvir in Germany. J Hepatol 2015; 62: S642-S643
    PubMedGoogle Scholar
  • 56 Najafzadeh M, Andersson K, Shrank WH et al. Cost-effectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med 2015; 162: 407-419
    CrossrefPubMedGoogle Scholar
  • 57 Younossi ZM, Park H, Saab S et al. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther 2015; 41: 544-563
    CrossrefPubMedGoogle Scholar
  • 58 Zhang S, Bastian ND, Griffin PM. Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US. BMC Gastroenterol 2015; 15: 98
    CrossrefPubMedGoogle Scholar
  • 59 Wiegand J, van Bömmel F, Duarte-Rojo A et al. Clinical Trial Watch: Reports from the Liver Meeting, AASLD, San Francisco, November 2015. J Hepatol 2016; pii: S0168-8278(16)00151-3 DOI: 10.1016/j.jhep.2016.02.020. [Epub ahead of print]
    PubMedGoogle Scholar
  • 60 Midgard H, Bjøro B, Mæland A et al. Hepatitis C reinfection after sustained virological response. J Hepatol 2016; pii: S0168-8278(16)00003-9 DOI: 10.1016/j.jhep.2016.01.001.
    PubMedGoogle Scholar