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G-Taliani
HCV: dalla terapia efficace allo screening di massa? Gloria Taliani Sapienza Università di Roma 1 Treated/cured patients represent only a small proportion of diagnosed ones… Eligibility Reliability Tolerability Efficacy North CS, et al. Gen Hosp Psych 2013;35:122–8. Advances in hepatitis C therapy with respect to tolerability and efficacy Dore GJ and Feld JJ. Clinical Infectious Diseases® 2015;60(12):1829–36 3 New DAAs in GT 1 cirrhotic patients: high rates of SVR with short duration regimens SVR (Compensated) SVR (Decompensated) SOF + PEG-IFN + RBV 12–24 81%1 43% (3/7)*2 SOF + RBV 24–48 36–78%3–5 68% (CTP B) 12–24 86–100%7,8 7/7 17 (CTP B) 79%20 94-100%18 60-86 19 SOF + SOF SMV + DCV ± RBV PTV/ OMV + DSV ± RBV RTV SOF 1. Duration (weeks) LDV ±RBV 12- 24 12–24 89–100%9 No data 12–24 86–100%10–14 60–90%15,16 Lawitz E, et al. N Engl J Med 2013;368:1878–87; 2. Forns X, et al. Hepatology 2015;61: 1485-94; 3. Gilead Sciences Europe Ltd. SOVALDI▼ (sofosbuvir), SmPC, March 2015; 4. Sulkowski MS, et al. JAMA 2014;312:353–61; 5. Molina JM, et al. Lancet. 2015;385:1098–106; 6. Afdhal N, et al. EASL 2014; Oral #68; 7. Lawitz E, et al. Lancet 2014;384:1756–65; 8. Janssen Products LP. OLYSIO▼(simeprevir), US PI, November 2014; 9. • AbbVie Ltd. VIEKIRAX▼ (ombitasvir/paritaprevir/ritonavir), SmPC, January 2015; ▼ 10. Afdhal N, et al. N Engl J Med 2014;370:1889–98; 11. Gilead Sciences Europe Ltd. HARVONI (ledipasvir/sofosbuvir), SmPC, November 2014; 12. Afdhal N, et al. N Engl J Med 2014;370:1483–93; 13. Reddy KR, et al. Hepatology 2015. doi: 10.1002/hep.27826; 14. Bourlière M, et al. Lancet Infect Dis 2015;15:397–404; 15. Flamm S, et al. AASLD 2014; Oral #239; 16. Reddy KR, et al. AASLD 2014; Oral #8 17. Reddy KR EASL 2015 Abst 0007. 18. Pol S et al EASL 2015 Abst LB03 19. Foster G et al EASL 2015 Abst 0002 20. Agel B et al AASLD 2014 Abst 19. *Post-transplant patients (n=22); †On-treatment response 95% at Week 24; ǂSee late breaker presentation (S. Pol; Abstract L03) at this meeting. DCV: daclatasvir; DSV: dasabuvir; GT: genotype; LDV: ledipasvir; OMV: ombitasvir; PEG-IFN: pegylated interferon; PI: prescribing information; PTV: paritaprevir; RBV: ribavirin; RTV: ritonavir; SmPC: Summary of Product Characteristics; 4 SMV: simeprevir; SOF: sofosbuvir Interferon-Free Direct Acting Antiviral Regimens for Chronic Hepatitis C Virus Genotype 1 Dore GJ and Feld JJ. Clinical Infectious Diseases® 2015;60(12):1829–36 5 12-week versus 6-week DAA Therapy naive pts (no cirrhosis). • HCV is a curable disease • No animal reservoir % SVR Kohli A et al. Lancet 2015; 384: 1107-13 In F3/F4 SVR 76% Kattakuzhy S et al. CID 2015 in press. • DAAs may provide nearly 100% efficacy (SVR) • In non-cirrhotic patients, treatment duration may become as short as 6-8 weeks • In cirrhotic patients maximum duration 12-24 weeks DISEASE CONTROL : reduction by ongoing interventions in morbidity and mortality ELIMINATION : No transmission/zero incidence, reduced prevalence to an «acceptable» level in a given region Continued interventions needed ERADICATION : Total absence of human cases. Interventions can be stopped Dowdle WR, WHO Bull 2006 Disease Control Hepatitis C Elimination Hepatitis C Eradication Significant/progressive disease High prevalence cohorts All HCV infected Disease Control Hepatitis C Elimination Hepatitis C Eradication Significant/progressive disease High prevalence cohorts All HCV infected Disease Control Hepatitis C Elimination Hepatitis C Eradication Significant/progressive disease High prevalence cohorts All HCV infected Three biological criteria are deemed important for disease eradication: Human beings the sole pathogen reservoir Existence of accurate diagnostic tests Availability of an effective, practical intervention at reasonable cost HEPATITIS C VIRUS THERAPEUTIC DEVELOPMENT: IN PURSUIT OF “PERFECTOVIR” REQUIREMENTS • Extremely high treatment efficacy (>95%) • Pangenotypic activity (i.e. similar dosing and duration) • Maintenance of high efficacy in all patients cathegories including decompensated and peritrasplant settings • Minimal toxicity and broad documented safety including renal failure, children, and pregnant women • High genetic barrier with minimal HCV resistance • Easy of dosing, preferably 1 table one daily • Limited DDI • Short duration • Affordability 12 Dore GJ and Feld JJ. Clinical Infectious Diseases® 2015;60(12):1829–36 PERSPECTIVES .. .. .. .. __ __ __ __ .__. .__. .__. UNDER-DIAGNOSIS and UNDER-TREATMENT : THE REAL BARRIERS Aghemo A et al. Journal of Viral Hepatitis 2015; 22: 1-3 HIGH-INCOME COUNTRIES DR : 30-60% INTERMEDIATE-INCOME COUNTRIES DR : 20-40% LOW-INCOME COUNTRIES DR : < 20% TR 2-6% TR 1-3% TR <1% Low prevalence Intermediate prevalence High prevalence Limited impact on global HCV disease burden of enhanced HCV treatment efficacy (SVR >90%), under current treatment rates Population impact calculated by multiplying efficacy figures (left) by % of individuals who have started HCV treatment. Thomas DL. Lancet. 2010 ; 376: 1441–1442. Limited impact on global HCV disease burden of enhanced HCV treatment efficacy (SVR >90%), under current treatment rates Population impact calculated by multiplying efficacy figures (left) by % of individuals who have started HCV treatment. Thomas DL. Lancet. 2010 ; 376: 1441–1442. The flow of the HCV disease progression model 16 Razavi H et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 34–59 The present and future disease burden of HCV infection with today’s treatment paradigm The most dramatic example of the impact of treatment rate was observed in France. Using today’s treatment paradigm, the total number of HCV infections is projected to decline slowly or remain flat in all countries. A high level of treatment with Peg-INF/RBV starting in 2000 led to a marked decrease in the number of infections. (Razavi H et al. Journal of Viral Hepatitis, 2014, 21, 34–59) STEPS AND REQUIREMENTS IN HCV ERADICATION/ELIMINATION/CONTROL BY ANTIVIRAL THERAPY • Highly effective/easy to use/universally available therapy: PERFECTOVIR • High diagnosis rates, effective link between diagnosis and treatment • Infra-structures, knowledge and capacity for high volume treatments • Treater’s and patient’s education and adherence • Treatment as prevention (reduced transmission) • Public awareness , strong advocacy and efficacious lobbying • Drug price reform 18 Dore GJ and Feld JJ. Clinical Infectious Diseases® 2015;60(12):1829–36 The estimated prevalence of chronic hepatitis C virus cases in the United States from 2001 to 2050 under different simulation scenarios. Natural History: no screening, no treatment Pre-DAA: risk-based screening and PR treatment Base case: risk-based and birth-cohort screening and Treatment (any kind) Ideal: universal screening, treatment (any kind) 2026 Kabiri M et al. Ann Intern Med. 2014 August 5; 161(3): 170–180. 2036 1/1500 (< 0.066%) FRANCE Wedemeyer H et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89 Scenario Base New DAA Treatment. Rate 5.2% 10.3% SVR 60% 90% Elegibility 60% 2013 90% 2016 FRANCE SPAIN Scenario Base New DAA Treatment Rate 2.1% 4.5% SVR 50% 90% Elegibility 50% 2013 90% 2018 Wedemeyer H et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89 Scenario Base New DAA Treatment. Rate 5.2% 10.3% SVR 60% 90% Elegibility 60% 2013 90% 2016 MAIN CONCLUSIONS ANNUAL TREATMENT RATE OF 10% TREATMENT IN >F2 TREATMENT IN F0-F1 HCV PREVALENCE > 90% BY 2030 LARGEST IMPACT ON DISEASE CONTROL TO REDUCE TRANSMISSION IN IDU TO ACHIEVE HCV ELIMINATION Wedemeyer H et al. Journal of Viral Hepatitis, 2014, 21, (Suppl. 1), 60–89 Mass screening is expensive Before adopting wide-scale screening, we must have a plan in place to care for infected individuals • The World Health Assembly passed two resolutions (63.18, May 2010 and A67/13 maggio 2013) that called for the World Health Organization to develop a comprehensive approach to control of chronic hepatitis. • ITALIAN PLAN “PNEV” launched on 6 November, 2015 EPIDEMIOLOGY PREVENTION SENSITIZATION, INFORMATION, FORMATION CURE and TREATMENT ACCESS SOCIAL IMPACT http://www.quotidianosanita.it/allegati/allegato9642946.pdf PNEV: modello attuativo 3 elementi cardine: 1.Identificazione delle aree prioritarie di intervento, definizione di azioni appropriate, tempi di realizzazione e responsabilità 2.Piena adesione e collaborazione con la Conferenza Stato-Regioni 3.Azione centralizzata di coordinamento e monitoraggio di applicazione/efficacia del PNEV, sotto la guida del Ministero della Salute. STIMA DEI PAZIENTI CON EPATITE C DIAGNOSTICATI ED ELEGGIBILI A UN TRATTAMENTO ANTIVIRALE CON I FARMACI INNOVATIVI (AL 1/1/2016) *E’ ipotizzabile che una percentuale possa essere già inclusa nei pazienti con altra esenzione, carcerati, TD Sono esclusi dal conteggio •Pazienti in tossicodipendenza attiva (non vi è indicazione terapeutica al momento) •Extracomunitari senza permesso di soggiorno (soggetti ad elevatissima mobilità) •Pazienti non ancora diagnosticati Ipotesi spesa farmaceutica cura pazienti HCV 2016 - 2023 1) Non sono conteggiate le nuove infezioni diagnosticate e ed i decessi (effetto compensativo) 2) Al netto delle risorse già stanziate per il 2016 di 500 Milioni * Costo farmaci ipotizzati in base alle informazioni disponibili, al netto dei pay back, rimborsi e note di credito. Nel caso il costo dei farmaci fosse inferiore, la stima si ridurrebbe in proporzione Studio e analisi: Associazione EpaC onlus Centre for Economic Evaluation and HTA (EEHTA), Università di Roma “Tor Vergata” Minimum Costs for Producing Hepatitis C DirectActing Antivirals for Use in Large-Scale Treatment Access Programs in Developing Countries The estimated costs in this analysis can only be justified if the eventual procurement of large (>1 Million) orders is guaranteed Hill A et al. Clinical Infectious Diseases 2014;58(7):928–36 Conclusions • Mass screening is expensive • Before adopting wide-scale screening, we must have a plan in place to care for infected individuals. • This plan should include an effort to improve education about HCV across health professions and to provide universal access to emerging treatments.