La cirrosi da HCV La del paziente: Linee guida a confronto · La selezione del paziente: Linee...

La cirrosi da HCVLa selezione del paziente: Linee guida a confronto

Massimo PuotiSC Malattie Infettive

AO Ospedale Niguarda Cà Granda

Massimo Puoti MD

Il sottoscritto dichiara di aver avuto negli ultimi 12 mesi conflitto d’interesse in relazione a questa presentazioneAbbvie, BMS, Gilead Sciences, Janssen, MSD, Roche,

Vertex e

che la presentazione non contiene discussione di farmaci in studio o ad uso off-label


• Linee guida e raccomandazioni• Chi deve essere trattato

• Priorità nel trattamento

• Come trattare• Dalle linee guida alla prescrivibilità


• Linee guida e raccomandazioni• Chi trattare



Guidelines

• A guideline is a statement by which to determine a course of action. A guideline aims to streamline particular processes according to a set routine or sound practice. ( U.S. Dept. of Veterans Affairs)

• Guidelines may be issued by and used by any organization (governmental or private) to make the actions of its employees or divisions more predictable, and presumably of higher quality

MAP

Recommendations

• Something (as a course of action) that is recommended as advisable to provide healthcare professionals with timely guidance

• Sentences of practical import, oriented to effecting an action

• Recommendations imply "ought‐to" types of statements and assertions, in distinction to sentences that provide "is" types of statements and assertions.

Linee guida e raccomandazioni

• Linee guida per la pratica clinica :• Punti fermi in un mondo in evoluzione lenta• Metodologia rigorosa e complessa• Benchmarking stabile per stakeholders• Base per la buona pratica clinica universale e quotidiana

• Raccomandazioni• Indicazioni di comportamento in un mondo che cambia rapidamente

• Metodologia agile ma autoreferenziale • Danno indicazione su nuove strade da percorrere

• All treatment‐naive patients with compensated disease due to HCV should be considered for therapy (recommendation A1)

• •Treatment should be scheduled, not deferred, for patients with significant fibrosis (METAVIR score F3 to F4) (recommendation A1)

• In patients with less severe disease, the indication for and timing of therapy can be individualized (recommendation B1)

• Cirrhosis • Patients with compensated cirrhosis should be treated, in the absence of contraindications, in order to prevent short‐to mid‐term complications (recommendation B2)

• In patients with Child‐Pugh B cirrhosis, antiviral therapy is offered on an individual basis in experienced centres, preferentially in patients with predictors of good response (recommendation C2)

• Patients with Child‐Pugh C cirrhosis should not be treated with the current IFN‐α‐based antiviral regimens, due to a high risk of life‐threatening complications (recommendation A1)

• Special populations • Indications for HCV treatment in HCV/HIV co‐infected persons are identical to those in patients with HCV mono‐infection (recommendation B2

• Hemodialysis patients, particularly those who are suitable candidates for renal transplantation, should be considered for antiviral therapy (recommendation A2). Antiviral therapy should be given to potential transplant recipients before listing for renal transplantation (recommendation B1)

• HCV treatment for PWID should be considered on an individualized basis and delivered within a multidisciplinary team setting (recommendation A1)

SELEZIONE DEI PAZIENTI: INIZIO O DIFFERIMENTO DELLA TERAPIA

Nel periodo di tempo che intercorre sino alla disponibilità di farmaci con maggiore efficacia si ritiene che alcune categorie di pazienti non debbano essere differiti, ma piuttosto ricevere un trattamento con i regimi basati su PegIFN/RBV ± TVR/BOC:

1. Pazienti con elevate probabilità di guarigione: ‐ pazienti naive con genotipo 1 e 4, con genotipo IL28 CC e/o RVR, bassa carica virale (HCV<400000 UI/ml); ‐ pazienti con genotipo 2/3 naive con segni di malattia; ‐ pazienti genotipo 1 relapsers non cirrotici

2. Pazienti naive con cirrosi epatica compensata senza segni diretti e indiretti di ipertensione portale (con valori di piastrine >100.000/mm3 e livelli sierici di albumina >35 gr/L) solo in centri con epatologi specializzati nella terapia antivirale di pazienti con malattia epatica avanzata e/o con epatologi esperti nell’ambito del trapianto di fegato.

3.Riceventi naive con epatite ricorrente post trapianto epatico con severità ≥F2 soprattutto se verificatasi entro il primo anno post trapianto, solo in centri con epatologi esperti nella gestione dei pazienti sottoposti a trapianto di fegato e in ogni caso in stretta collaborazione con l’epatologo di riferimento del centro trapianti .

4. Pazienti naive con manifestazione extra‐epatiche di HCV, specialmente con sindrome crioglobulinemica sintomatica

WHO GUIDELINES

• WHO recommends that all adults and children with chronic HCV infection, including people who inject drugs, should be assessed for receiving treatment for HCV. (Strong recommendation, moderate quality of evidence)

• Based on these considerations, currently patients with more advanced fibrosis and cirrhosis (METAVIR F3 and F4 stages) should be prioritized for treatment.

• However, there are no population‐based data to indicate how many persons meet these criteria. Furthermore, this prioritization may change, as safer and more effective medicines become available, assuming that they are affordable.

WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONS

Indications to treatment

All treatment‐naïve and ‐experienced patients with compensated disease due to HCV should be considered for therapy (A1)

Treatment is recommended for patients with chronic HCV infection (IA)

WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONSCIRRHOSIS

Clinical setting

Compensated Cirrhosis

Strongly recommended (A1)

Highest priority (IA)

Decompensated cirrhosis not on the transplant list

On clinical trial or expanded accessprogram or within experienced centres (B1)

treated by physicians with experience in treating HCV in conjunction with aliver transplantation center

WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONSNON CIRRHOTICS: DISEASE STAGING

Clinical setting

F3 Strongly recommended (A1)

Highest priority (IA)

F2 Justified (A2) High priority (IB)

F0‐F1 Indication for and timing of therapy can beIndividualized (B1)

Individual decision (IB)

WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONSHCV related extrahepatic diseases & Comorbidities 1

Clinical setting

Cryoglobulinemia with vasculitis Treatment should be

prioritized (A1)

Highest priority (IB)

HCV related immune complex Nephropathy

Highest priority (IIaB)

Solid Organ Transplant Recipients

No specific priority (A2) considered for individual decision


Haemodialysis Should be considered (B1)

Consider treatment prioritization In order to yield transmission reduction benefits (IIaC)

HIV No specific priority (A1) considered for individual decision

High priority based on available resources(IB)

Clinical setting

HBV No specific priority (B1) considered for individual decision

High priority based on available resources (IIaC)

NASH & other liver disease No specific priority

Haemoglobinopathies No specific priority considered for individual decision (B2)

No specific priority

Bleeding disorders No specific priority considered for individual decision (A1)


Clinical setting

Type II Diabetes No specific priority considered for individual decision

High priority based on available resources (IIaB)

Debilitating fatigue

MSM with high risk sexual practicesPrisoners Consider treatment

prioritization In order to yield transmission reduction benefits ( IIaC)

Persons Who Inject Drugs On an individualized basis,but those with early liver disease can be advised to await further data and/or potential development of improved therapies (B2)


Treatment of HIV/HCV coinfectionAASLD guidelines 2014

Naïve or Relapsers

Eligible to Interferon

HCVG1 HCV G2 HCV G3 HCV G4

Yes Yes PR + Sofo 12 w alt. [IB]

Sofo + R (cirrh 16 w) [IB]

Sofo + R 24 w [I B]

PR+ Sofo 12 w [IIaB]

PR + Sime 24‐48w [IIaC]

PR + Sime 24‐48w

No Sofo + R [IB]Sofo + R 24 w [IIaC]

Sofo + Sime +Riba [IIaC]

No Yes Sofo + Sime + R

[IIaC]

PR + Sofo 12 w [IIaB]

PR + Sofo 12 w [IIaA]

PR + Sofo 12 w [IIaB]

Sofo + R 12 w (16w cirrh.) [IB]

Sofo + R 24 w [IIaB]

Sofo + R 24 w [IIaC]No

Treatment Options if Sofosbuvir, Simeprevir and Daclatasvir are available

PegIFN + ribavirin + sofosbuvir

PegIFN + ribavirin + simeprevir

PegIFN + ribavirin + daclatasvir

Sofosbuvir + ribavirin

Sofosbuvir + simeprevir (± ribavirin)

Sofosbuvir + daclatasvir (± ribavirin)

12 weeks

12 weeks+RGT 12/36

12 weeks+ 12

12-24 weeks

12 weeks

12-24 weeks

Courtesy from JM Pawlotsky: EASL 2014; available on www.easl.ch

Anti HCV Tx in patients with Cirrhosis

Regimen Compensated also on LT list

Decomp. on LT list

HCV Genotype 1&4 2 3 1&4 2 3PR + SOFO 12 w §

PR + SIME 48 w @PR + DAC 24 w ^SOFO + R 12‐24 w # * # * #

SOFO + DAC + R 12‐24 w°SOFO + SIME + R 12‐24 w°

§ 1st choice in experienced; # for 24 weeks; * for 16 weeks in experienced; ° 24 weeks in pts with poor predictors of response: HCVG1a and/or experienced@ not indicated in HCV G1a Q80K+ ^ not indicated in HCV G1a

1st choice; 2nd choice; 3rd choice

Treatment of HIV/HCV coinfectionAASLD guidelines 2014

Naïve or Relapsers

Eligible to Interferon

HCVG1 HCV G2 HCV G3 HCV G4

Yes Yes 60.000 Euro

60‐80.000 Euro

120.000 Euro

60.000 Euro

40.000 Euro 40.000 Euro

No 120.000 Euro 120.000 Euro

100.000 EuroNo Yes 60.000 Euro

120.000 Euro

120.000 EuroNo

National Institute for Health and Care Excellence (NICE) consults on further draft guidance on the drug

sofosbuvir (Sovaldi) for treating hepatitis CICER: £ per QUALY gained with Sofosbuvir

HCV G1 HCV G3

Vs PR VS PR + BOC/TEL Vs PR

PR + SOFO Naives 17,500Exp 12,600

Naives 10,300 / 15,400 Exp 700/8200

Naives With Cirr 6,600Non cirr 40,600Exp 19,000

HCV G1 HCV G2 HCV G3

Vs no tx Vs PR Vs no Tx Vs no Tx

SOFO + R 47,500 Tx naives 46,300Tx exp 12,500

IFN Intolerant Ineligible 12,500

Cirrhosis Naives 10,500Exp 19,200Non cirr

Naïve 28,000Exp 31,400

https://www.nice.org.uk/news/press-and-media/NICE-consults-on-draft-guidance-on-the-drug-sofosbuvir-for-treating-hepatitis-C last visit August 18th 2014

Cost of sofosbuvir 11,660.98 £ + VAT per 28-tablet pack (BNF May 2014). 12-week course 34,982.94 £ + VAT and a 24-week course 69,965.88 £ + VAT

The cost‐effectiveness of improved hepatitis C virustherapies in HIV/hepatitis C virus coinfected patients

Linas BP et al AIDS 2014, 28:365–376

MEDICAID

• Medicaid è un programma federale sanitario degli Stati Uniti d'America che provvede a fornire aiuti agli individui e alle famiglie con basso reddito salariale.

• È finanziato sia dal governo federale che dai governi dei singoli stati ed è gestito da questi ultimi. La partecipazione degli stati però, secondo la legge, è volontaria ma tutti gli stati lo hanno adottato; l'ultimo è stato l'Arizona nel 1982.

WHOM TO TREAT ACCORDING TO MEDICAID :FROM GUIDELINES TO PRESCRIPTION AUTHORIZATION

Clinical setting NYS Medicaid Rhode Island Medicaid

Pennsylvania Medicaid

F3 F4 Highest priority (IA)

Histology Stiffness > 9.5 Fibrosure > 0.58 APRI > 1.5 Portal hypertension on radiological imaging

HistologyAPRI > 1

Fibroscan > 9.5 Fibrotest > 0.58

Imaging consistent with

cirrhosis

Methods not specified

F2 High priority (IB)

F0‐F1 Individual decision (IB)


Clinical setting Rhode Island Mdicaid

Pennsylvania Medicaid

Cryoglobulinemia with vasculitis


HCV related immune complex Nephropathy

Highest priority (IIaB)

Solid Organ Transplant Recipients


Haemodialysis Consider treatment prioritization In order to yield transmission reduction benefits (IIaC)

HIV High priority based on available resources(IB)

NYS Medicaid

Clinical setting

Rhode Island Medicaid

Pennsylvania

HBV High priority based on available resources (IIaC)

NASH & other liver disease

Type II Diabetes

Debilitating fatigue

PWID on Opiate subst treatment

Yes if no illicit drug use from 6 mo

Yes if no illicit drug use from 6 mo

PWID, MSM, Prisoners


La cirrosi da HCVLa selezione del paziente: Linee guida a confronto• Linee guida: mappe• Raccomandazioni: bussola per un viaggio in territori poco conosciuti• Chi trattare: la terapia va considerata in tutti i pazienti

• Tutti i cirrotici compensati che hano la priorità più elevata • Cirrotici scompensati non in lista trapianto: indicazioni discordanti• Priorità in pazienti non cirrotici:

• Concordanza su Crioglobuinemia sintomatica e Nefropatie HCV correlate• Discordanza sulle altre categorie

• Come trattare: • diverse opzioni di terapia basate sul genotipo • IFN free: terapia preferenziale ove disponibile nel cirrotico

• Dalle linee guda alla prescrivibilità: • Entrano in campo “cost effectiveness”(ICER per QUALY) e sostenibilità• Medicaid: Interpretazione eterogenea e contradittoria• Un esempio per il SSN italiano?

La cirrosi da HCV La del paziente: Linee guida a confronto · La selezione del paziente: Linee...

Documents

Transcript of La cirrosi da HCV La del paziente: Linee guida a confronto · La selezione del paziente: Linee...