LA GOVERNANCE DELL’INNOVAZIONE NELLA GESTIONE DELL’EPATITE C

Appropriatezza e valutazione esitiDr. Moretti Vincenzo

Ancona12 aprile 2017

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)

LA SCELTA DELLO SCHEMA DI TERAPIA

1) Il panel dei farmaci è, al momento, 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

N. di trattamenti nella Ragione Marche per criterio

AIFA al 15/07/2015

N. di trattamenti nella Ragione Marche per criterio

AIFA al 12/04/2017

TRATTAMENTI PER GENOTIPO ad oggi AOR

I farmaci disponibiliSchemi terapeutici ottimali per genotipi

Genotipo Schema terapeutico Durata terapia Note

Genotipo 1

Harvoni +/- RBV 12-set

Harvoni 24-setSe cirrotico

intollerante a RBV

Viekirax+Exviera 12-setGenotipo 1b

Viekirax+Exviera +

RBV12-set

Genotipo 1b con

cirrosi compensata

Child-Pugh A e B

Viekirax+Exviera +

RBV12-setGenotipo 1a

Viekirax+Exviera +

RBV24-set

Genotipo 1b con

cirrosi compensata

Child-Pugh A e B

Sovaldi + Daklinza

+/- RBV12-set

Sovaldi + Daklinza 24-setSe cirrotico

intollerante a RBV

Sovaldi + Olysio +/-

RBV12-set

I farmaci disponibiliSchemi terapeutici ottimali per genotipi

Genotipo Schema terapeutico Durata terapiaNote

Genotipo 2Sovaldi + RBV 12-set

Sovaldi + RBV 16-set Se cirrotico

Genotipo 3

Sovaldi + Daklinza +/-

RBV12-set

Sovaldi + Daklinza +/-

RBV24-set Se cirrotico

Sovaldi + RBV 24-set

I farmaci disponibiliSchemi terapeutici ottimali per genotipi

Genotipo Schema terapeutico Durata terapia Note

Genotipo 4

Harvoni + RBV 12-set

Harvoni 24-setSe cirrotico

intollerante a RBV

Viekirax + RBV 12-set

Viekirax + RBV 24-setSe cirrotico

Sovaldi + Daklinza

+/- RBV12-set

Sovaldi + Daklinza 24-setSe intollerante a RBV

Sovaldi + Olysio +/-

RBV12-set

VALUTAZIONE DELL’EFFICACIA

Oral Direct-Acting Agent Therapy for Hepatitis C Vi rus Infection: A Systematic Review.

Falade-Nwulia et al. Ann Intern Med. 2017 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 res ponse (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.

Efficacia e sicurezza dei DAA nel genotipo 1

con o senza ribavirina

Efficacy and Safety of Ledipasvir/Sofosbuvir with a nd without Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: a meta-analysis .

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 sign ificantly 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 disconti nuation. LDV- SOF plus RBV therapy had significantly higher rate of the ov erall adverse eventsThis 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. 2017 Feb;55:56-71. doi: 10.1016/j.ijid.2016.12.023. Epub 2016 Dec 29.

VALUTAZIONE DELL’EFFICACIA: GENOTIPO 3

Closing the Gap: The Challenges of Treating Hepatit is C Virus Genotype 3 Infection.Martin MT1,2, Deming P3. Pharmacotherapy. 2017 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 treatment-experienced 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 treatmentRESULTS: Given the limited data and observed SVR rates in th is patient population, the optimal therapy for patients with d ecompensated cirrhotic GT 3 HCV infection is not yet established. Newer ag ents and recommendations regarding baseline resistance are l ikely to evolve treatment strategies in the near future.

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 ca re setting..Bach TA1, Zaiken K2Am J Health Syst Pharm. 2017 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 overa ll sustained virologicresponse (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 missin g at least one dose of medication.

Le interazioni ed ADR

World J Gastroenterol. 2017 Mar 7;23(9)Optimizing hepatitis C virus treatment through pharmac ist interventions: Identification and management of drug-drug interactio ns.

Langness JA1, Nguyen M1, Wieland A1, Everson GT1, Kiser JJ1.

664 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 mo nitoring 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.

Dati di efficacia (valutata come pazienti che hanno terminato la terapia o che non hanno interrotto)

464

56

8 3

531

0

100

200

300

400

500

600

a termine

in corso

interruzioe

cambio terapia

totale

Dati di efficacia cumulativa(valutata come pazienti che hanno terminato la terapia o che non hanno interrotto)

87%

10%

2% 1%

a termine

in corso

interruzioe

cambio terapia

Dati di efficacia per i 4 schemi più impiegati in AOR Ancona

DAC+SOF +/-

RIBAVIRINALED/SOF± RIB AVIRINA

SIM+SOF ± RIBAVIRINASOF + RIBAVIRINA

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

In conclusione:

• Nel panorama della terapia per HCV oggi sono disponibili farmaci altamente efficaci

• In base ai criteri AIFA, al genotipo e alle condizio ni cliniche del paziente, sono disponibili diversi regi mi terapeutici efficaci

• La scelta del regime terapeutico tra quelli indicati/efficaci deve essere fatta tenendo conto d el costo che il SSR deve sostenere ed al migliore outcome

• Vanno segnalate tutti i casi di intolleranza o tossi cità(spesso attribuibili alla ribavirina)

• Occorre promuove l’utilizzo appropriato costo/efficace di altri farmaci (LIBERARE RISORSE)

• Senza una collaborazione stretta clinico-paziente-farmacista-regolatorio, si corre il rischio di non spendere in modo costo/efficace accettabile