Appropriatezza e valutazione esiti

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1 Ancona12 aprile 2017 LA GOVERNANCE DELL INNOVAZIONE NELLA GESTIONE DELL EPATITE C Appropriatezza e valutazione esiti Dr. Moretti Vincenzo

2 introduzione Le diverse angolature del trattamento: i soggetti(paziente, specialista, MMG, il personale sanitario) le risorse(indispensabili) i costi(importanti) l approccio terapeutico appropriato(criteri AIFA e sostenibilità dei regimi terapeutici) efficacia vs tossicità vs tollerabilità vs costi(il punto di vista dello specialista, dell amministratore, del paziente) le regole(una gabbia, una sicurezza, una burocrazia)

3 LA SCELTA DELLO SCHEMA DI TERAPIA 1) Ilpaneldeifarmaciè,almomento,adeguato: Il clinico ha a disposizione nuove opzioni terapeutiche; Si determina una maggiore concorrenza tra ditte e la riduzione dei prezzi 2) Non esistono studi testa a testa di efficacia tra i vari farmaci/regimi terapeutici disponibili 3) E lecito affermare che, tra i regimi terapeutici attualmente disponibili, debbano essere scelti quello/i che, a parità di efficacia, sicurezza e tollerabilità, presentano il miglior rapporto costo/opportunità

4 N. di trattamenti nella Ragione Marche per criterio AIFA al 15/07/2015

5 N. di trattamenti nella Ragione Marche per criterio AIFA al 12/04/2017

6 TRATTAMENTI PER GENOTIPO ad oggi AOR

7 Schemi terapeutici ottimali per genotipi I farmaci disponibili Genotipo Schema terapeutico Durata terapia Note Genotipo 1 Harvoni +/- RBV Harvoni Viekirax+Exviera Viekirax+Exviera + RBV Viekirax+Exviera + RBV Viekirax+Exviera + RBV Sovaldi + Daklinza +/-RBV Sovaldi + Daklinza Sovaldi + Olysio +/- RBV 12-set Se cirrotico 24-set intollerante a RBV 12-set Genotipo 1b Genotipo 1b con 12-setcirrosi compensata Child-Pugh A e B 12-set Genotipo 1a Genotipo 1b con 24-setcirrosi compensata Child-Pugh A e B 12-set Se cirrotico 24-set intollerante a RBV 12-set

8 Schemi terapeutici ottimali per genotipi Genotipo Schema terapeutico Durata terapia I farmaci disponibili Note Genotipo 2 Genotipo 3 Sovaldi + RBV Sovaldi + RBV Sovaldi + Daklinza +/- RBV Sovaldi + Daklinza +/- RBV Sovaldi + RBV 12-set 16-set Se cirrotico 12-set 24-set Se cirrotico 24-set

9 Schemi terapeutici ottimali per genotipi I farmaci disponibili Genotipo Schema terapeutico Durata terapia Note Genotipo 4 Harvoni + RBV Harvoni Viekirax + RBV Viekirax + RBV Sovaldi + Daklinza +/-RBV Sovaldi + Daklinza Sovaldi + Olysio +/- RBV 12-set Se cirrotico 24-set intollerante a RBV 12-set 24-set Se cirrotico 12-set 24-set Se intollerante a RBV 12-set

10 VALUTAZIONE DELL EFFICACIA Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review. Falade-Nwulia et al. Ann Intern Med Mar 21 STUDY SELECTION: 42 studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs. RESULTS: Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without.

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13 Efficacia e sicurezza dei DAA nel genotipo 1 con o senza ribavirina Efficacy and Safety of Ledipasvir/Sofosbuvir with and without Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: a metaanalysis. We performed a meta-analysis to assess the efficacy and safety of the LDV- SOF with and without RBV in treating HCV genotype 1 patients. Seven studies involving 2,626 patients. The addition of RBV to LDV- SOF regimen neither significantly improved sustained viral response at 12 weeks (SVR12) after the last dose of treatment, nor decreased virologic breakthrough and relapse. There was no significant difference in the incidence of discontinuation. LDV- SOF plus RBV therapy had significantly higher rate of the overall adverse events This meta-analysis suggests that LDV-SOF based therapy is a safe and effective treatment for patients with GT 1 HCV. The addition of RBV to LDV-SOF may increase toxicity without achieving improved efficacy. Tao T1, Jiang X1, Chen Y2, Song Y3. Int J Infect Dis Feb;55: doi: /j.ijid Epub 2016 Dec 29.

14 VALUTAZIONE DELL EFFICACIA: GENOTIPO 3 Closing the Gap: The Challenges of Treating Hepatitis C Virus Genotype 3 Infection. Martin MT1,2, Deming P3. Pharmacotherapy Apr 4 CONTEST:The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatmentexperienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Our objective was to review the SVR rates with available and late-pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment RESULTS: Given the limited data and observed SVR rates in this patient population, the optimal therapy for patients with decompensated cirrhotic GT 3 HCV infection is not yet established. Newer agents and recommendations regarding baseline resistance are likely to evolve treatment strategies in the near future.

15 VALUTAZIONE DELL EFFICACIA NEL GENOTIPO 1 E 4 Outcomes of treatment with direct-acting antivirals for infection with hepatitis C virus genotypes 1-4 in an ambulatory care setting.. Bach TA1, Zaiken K2 Am J Health Syst Pharm Mar 1;74(5 Supplement 1) STUDY: A total of 360 patients at 36 clinical sites in Massachusetts with HCV genotypes 1-4 and a prescription for at least one DAA medication between May 2011 and October 2015 were included RESULTS: About half of the patients were treatment naive (TN), and 40% of patients had documented cirrhosis. TN patients without cirrhosis had the highest overall sustained virologic response (SVR) rate at 107 of 109 (98.2%), followed by treatment-experienced (TE) patients without cirrhosis at 59 of 63 (93.7%), TN patients with cirrhosis at 40 of 46 (87.0%). A total of 7 of 360 (1.9%) patients reported missing at least one dose of medication.

16 Le interazioni ed ADR World J Gastroenterol Mar 7;23(9) Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions. Langness JA1, Nguyen M1, Wieland A1, Everson GT1, Kiser JJ patients: 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients.

17 Dati di efficacia (valutata come pazienti che hanno terminato la terapia o che non hanno interrotto) a termine in corso interruzioe cambio terapia totale

18 Dati di efficacia cumulativa(valutata come pazienti che hanno terminato la terapia o che non hanno interrotto) 2% 1% 10% a termine in corso interruzioe cambio terapia 87%

19 Dati di efficacia per i 4 schemi più impiegati in AOR Ancona DAC+SOF +/- RIBAVIRINA LED/SOF± RIB AVIRINA SIM+SOF ± RIBAVIRINA SOF + RIBAVIRINA

20 SINERGIA TRA: Medico specialista Amministratore Farmacia Agenzie sanitarie regionali Paziente e familiari Industria farmaceutica Associazioni di pazienti GESTIRE IL PRESENTE E PROGRAMMARE IL FUTURO Programmare per quanto possibile l accesso alle cure Attivare percorsi diagn.ter.assist. condivisi Monitorare l efficacia e la tollerabilità Gestire la logistica, gli acquisti, le registrazioni, i rimborsi

21 In conclusione: Nel panorama della terapia per HCV oggi sono disponibili farmaci altamente efficaci In base ai criteri AIFA, al genotipo e alle condizioni cliniche del paziente, sono disponibili diversi regimi terapeutici efficaci La scelta del regime terapeutico tra quelli indicati/efficaci deve essere fatta tenendo conto del costo che il SSR deve sostenere ed al migliore outcome Vanno segnalate tutti i casi di intolleranza o tossicità (spesso attribuibili alla ribavirina) Occorre promuove l utilizzo appropriato costo/efficace di altri farmaci (LIBERARE RISORSE) Senza una collaborazione stretta clinico-pazientefarmacista-regolatorio, si corre il rischio di non spendere in modo costo/efficace accettabile