Transcript Linee guida a confronto

La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
Massimo Puoti
SC 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 presentazione
Abbvie, BMS, Gilead Sciences, Janssen, MSD, Roche,
Vertex
e
che la presentazione non contiene discussione
di farmaci in studio o ad uso off-label
La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
• Linee guida e raccomandazioni
• Chi deve essere trattato
• Priorità nel trattamento
• Come trattare
• Dalle linee guida alla prescrivibilità
La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
• Linee guida e raccomandazioni
• Chi trattare
• Priorità nel trattamento
• Come trattare
• Dalle linee guida alla prescrivibilità
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 :
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•
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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 La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
• Linee guida e raccomandazioni
• Chi deve essere trattato
• Priorità nel trattamento
• Come trattare
• Dalle linee guida alla prescrivibilità
• 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 All treatment‐naïve and ‐ Treatment is treatment
experienced patients recommended for with compensated patients with disease due to HCV chronic HCV should be considered for infection (IA)
therapy (A1)
La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
• Linee guida e raccomandazioni
• Chi deve essere trattato
• Priorità nel trattamento
• Come trattare
• Dalle linee guida alla prescrivibilità
WHOM TO TREAT:
EASL AND AASLD‐IDSA RECOMMENDATIONS
CIRRHOSIS
Clinical setting
Compensated Cirrhosis
Strongly recommended (A1) Highest priority (IA) Decompensated cirrhosis not on the transplant list
On clinical trial or expanded access
program or within experienced centres (B1) treated by physicians with experience in treating HCV in conjunction with a
liver transplantation center
WHOM TO TREAT:
EASL AND AASLD‐IDSA RECOMMENDATIONS
NON CIRRHOTICS: DISEASE STAGING
Clinical setting
F3
Strongly recommended (A1) Highest priority (IA) F2
Justified (A2) High priority (IB) F0‐F1
Indication for and timing Individual decision (IB) of therapy can be
Individualized (B1) WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONS
HCV related extrahepatic diseases & Comorbidities 1
Clinical setting
Cryoglobulinemia with vasculitis
HCV related immune complex Nephropathy
Highest priority (IB)
Treatment should be prioritized (A1)
Highest priority (IIaB)
Solid Organ Transplant Recipients
No specific priority (A2) considered for individual decision
Highest priority (IB)
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)
WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONS
HCV related extrahepatic diseases & Comorbidities 2
Clinical setting
HBV
No specific priority (B1) considered for individual decision
NASH & other liver disease
No specific priority
Haemoglobinopathies
No specific priority considered for individual decision (B2)
Bleeding disorders
No specific priority considered for individual decision (A1) High priority based on available resources (IIaC)
No specific priority WHOM TO TREAT:EASL AND AASLD‐IDSA RECOMMENDATIONS
HCV related extrahepatic diseases & Comorbidities 3
Clinical setting
Type II Diabetes
Debilitating fatigue
No specific priority considered for individual decision MSM with high risk sexual practices
Prisoners
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)
High priority based on available resources (IIaB)
Consider treatment prioritization In order to yield transmission reduction benefits ( IIaC) La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
• Linee guida e raccomandazioni
• Chi deve essere trattato
• Priorità nel trattamento
• Come trattare
• Dalle linee guida alla prescrivibilità
Treatment of HIV/HCV coinfection
AASLD guidelines 2014
Naïve or Relapsers Eligible to Interferon Yes
Yes HCVG1
HCV G3
PR + Sofo 12 w alt. [IB]
PR + Sime 24‐
48w [IIaC]
No
HCV G2
Sofo + R [IB]
PR+ Sofo 12 w [IIaB]
Sofo + R (cirrh 16 w) [IB] Sofo + R 24 w [I B]
Yes Sofo + Sime + R [IIaC]
No PR + Sime 24‐48w
Sofo + R 24 w [IIaC]
Sofo + Sime +
Riba [IIaC]
No HCV G4
PR + Sofo 12 w [IIaB]
PR + Sofo 12 PR + Sofo 12 w [IIaA]
w [IIaB]
Sofo + R 12 w (16w cirrh.) [IB]
Sofo + R 24 w [IIaB]
Sofo + R 24 w [IIaC]
Treatment Options if Sofosbuvir, Simeprevir and Daclatasvir are available
PegIFN + ribavirin + sofosbuvir
12 weeks
PegIFN + ribavirin + simeprevir
12 weeks
+RGT 12/36
PegIFN + ribavirin + daclatasvir
12 weeks
+ 12
Sofosbuvir + ribavirin
12-24
weeks
Sofosbuvir + simeprevir (± ribavirin)
12 weeks
Sofosbuvir + daclatasvir (± ribavirin) 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 HCV Genotype
1&4
2
3
Decomp. on LT list
1&4
2
3
*
#
§
PR + 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;  2nd choice;  3rd choice
§ 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
La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
• Linee guida e raccomandazioni
• Chi deve essere trattato
• Priorità nel trattamento
• Come trattare
• Dalle linee guida alla prescrivibilità
Treatment of HIV/HCV coinfection
AASLD guidelines 2014
Naïve or Relapse
rs Eligible HCVG1
to Interfer
on Yes
Yes HCV G2
60.000 Euro
No Yes No 120.000 Euro
100.000 Euro
HCV G4
60.000 Euro
120.000 Euro
40.000 Euro
No
HCV G3
60‐80.000 Euro
40.000 Euro
120.000 Euro
60.000 Euro
120.000 Euro
120.000 Euro
National Institute for Health and Care Excellence (NICE)
consults on further draft guidance on the drug
sofosbuvir (Sovaldi) for treating hepatitis C
ICER: £ per QUALY gained with Sofosbuvir HCV G1
PR + SOFO
Vs PR
VS PR + BOC/TEL
Vs PR
Naives 17,500
Exp 12,600 Naives 10,300 / 15,400 Exp 700/8200
Naives With Cirr 6,600
Non cirr 40,600
Exp 19,000
HCV G1
SOFO + R HCV G3
HCV G2
HCV G3
Vs no tx
Vs PR
Vs no Tx Vs no Tx 47,500
Tx naives 46,300
Tx exp 12,500
IFN Intolerant Ineligible 12,500
Cirrhosis Naives 10,500
Exp 19,200
Non cirr Naïve 28,000
Exp 31,400
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
https://www.nice.org.uk/news/press-and-media/NICE-consults-on-draft-guidance-on-the-drugsofosbuvir-for-treating-hepatitis-C last visit August 18th 2014
The cost‐effectiveness of improved hepatitis C virus
therapies 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
F3 F4
Highest priority (IA) F2
High priority (IB) F0‐F1
Individual decision (IB) NYS Medicaid
Rhode Island Medicaid
Pennsylvania Medicaid
Histology Stiffness > 9.5 Fibrosure > 0.58 APRI > 1.5 Portal hypertension on radiological imaging Histology
APRI > 1
Fibroscan > 9.5 Fibrotest > 0.58
Imaging consistent with cirrhosis
Methods not specified
WHOM TO TREAT ACCORDING TO MEDICAID :
FROM GUIDELINES TO PRESCRIPTION AUTHORIZATION
NYS Medicaid
Clinical setting
Cryoglobulinemia with vasculitis
Highest priority (IB)
HCV related immune complex Nephropathy
Highest priority (IIaB)
Solid Organ Transplant Recipients
Highest priority (IB)
Haemodialysis
Consider treatment prioritization In order to yield transmission reduction benefits (IIaC)
HIV
High priority based on available resources(IB)
Rhode Island Mdicaid
Pennsylvania Medicaid
WHOM TO TREAT ACCORDING TO MEDICAID :
FROM GUIDELINES TO PRESCRIPTION AUTHORIZATION
Clinical setting
HBV
NASH & other liver disease
Rhode Island Pennsylvania
Medicaid
High priority based on available resources (IIaC)
Type II Diabetes
Debilitating fatigue
PWID on Opiate subst treatment
PWID, MSM, Prisoners
Yes if no illicit drug use from 6 mo Yes if no illicit drug use from 6 mo La cirrosi da HCV
La selezione del paziente: Linee guida a confronto
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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?