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Kings College Hepatitis C Outreach


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Kings College Hepatitis C Outreach

  1. 1. Hepatitis C (Treatments & how to give them…) Current and upcoming treatments Outreach into drug and alcohol centres Peer Advocacy Stephanie Broughton, GSTT BBV CNS Rebecca Hawley, KCH Viral Hepatitis CNS Sarah Hodges, KCH Viral Hepatitis CNS Ala Miah, Groundswell Peer Mentor
  2. 2. Antiviral Therapy for the treatment of chronic HCV Sarah Hodgson Viral Hepatitis CNS, Kings College Hospital. March 2015
  3. 3. ANTIVIRAL TREATMENTS FOR HCV ARE EVOLVING RAPIDLY • Pegylated Interferon+ Ribavirin +/- first generation DAA’s (PI’s) - Telaprevir (TPV) or Boceprevir (BCV) for 24-48 weeks depending on medication, prior treatment status, disease stage and on treatment response • Simeprevir (Olysio) NICE approved in the past two months or so with accompanying NHSE statement, given with Pegylatd Inteferon and Ribavirin MOST PATIENTS ARE CHOOSING TO WAIT FOR ANTIVIRAL MEDICATIONS WITH SHORTER DURATIONS, FEWER SIDE EFFECTS AND HIGHER RESPONSE RATES Current NICE approved G1 treatment regimes:
  4. 4. SIMEPREVIR – AS NHSE STATEMENT ONLY • HCV genotype 1, treatment naïve, prior relapsers and non responders. • HIV co-infection, but there are drug to drug interactions with certain antiretroviral drugs such as Effavirenz • NOT for PI failures • G1a – need to be Q80 k negative • NOT for cirrhosis Child-Pugh B 7 or above, or cirrhosis with signs of decompensation • 12 weeks triple therapy with Pegylated Interferon and Ribavirin + Simeprevir then 12 weeks Pegylated Interferon and Ribavirin in treatment naïve patients and relapsers or 24 weeks in non responders • Some DDI’s • Side effects similar to Telaprevir but much milder – anaemia, rash, pruritis, hypersensitivty, photosensitivity, dyspnoea NHSE (January 2015): Interim Clinical Commissioning Statement: Simprevir for treating Genotype 1 Chronic Hepatitis C
  5. 5. SIMEPREVIR STOPPING RULES Treatment week HCV RNA Action 4 Greater than or equal to 25 IU/Ml Discontinue treatment, drug company will reimburse Simeprevir 12 Greater than or equal to 25 IU/Ml Discontinue treatment, drug company will reimburse Simeprevir 24 Greater than or equal to 25 IU/Ml Discontinue Pegylated Interferon and Ribavirin
  6. 6. Treatment-naive pts with GT 1 HCV (N = 391) Simeprevir 150 mg QD + P/R† (n = 257) Randomized 2:1*; stratified by GT 1 subtype, IL28B genotype P/R *63% of patients in each arm were randomly assigned to receive pegIFN alfa-2a or pegIFN alfa-2b; the remainder were assigned pegIFN alfa-2a. † RGT: Patients with HCV RNA < 25 IU/mL at Wk 4 and HCV RNA undetectable at Wk 12 received a total of 24 wks of therapy. Those not achieving this on-treatment response received 48 wks of therapy. Placebo + P/R (n = 134) P/R P/R QUEST-2: SIMEPREVIR + P/R RGT IN TREATMENT-NAIVE GT 1 HCV  Phase III, randomized, double-blind, placebo-controlled trial  7% to 11% had cirrhosis, 58% had GT 1b HCV Wk 24 Wk 48Wk 12 Manns M, et al. EASL 2013. Abstract 1413.
  7. 7. QUEST-2: VIROLOGIC RESPONSE TO SIMEPREVIR + P/R TREATMENT Manns M, et al. EASL 2013. Abstract 1413. Reproduced with permission. SMV Arm: Total Duration of RGT 91% of pts in SMV arm met RGT criteria n/N = SMV + P/R P/R Overall 24 wks 48 wks 100 80 60 40 20 0 SVR12(%) 81 50 86 32 209/257 67/134 202/235 7/22
  8. 8. NON G1 CURRENTLY NICE APPROVED THERAPIES • Pegylated Interferon and Ribavirin only • Genotype 2 – usually 24 weeks, around 80% SVR rates • Genotype 3 – usually 24-36 weeks, 60-70% SVR rates but G3a may be less • Genotype 4 – usually 48 weeks, 66% SVR rates, SMV now NICE approved but no NHSE statement • Many patients are choosing to wait for new therapies due to the side effects of Pegylated Interferon and Ribavirin
  9. 9. Type of hepatitis C Sofosbuvir with peginterferon alfa and ribavirin Sofosbuvir with ribavirin alone Genotype 1 Recommended by NICE Not recommended by NICE Genotype 2 Not licensed Recommended only if: •the person’s hepatitis C has not been treated before and they cannot have interferon or •the person’s hepatitis C has been treated before but has not responded well enough. Genotype 3 Recommended only if: •the person’s hepatitis C has not been treated before and they have cirrhosis or •the person’s hepatitis C has been treated before but has not responded well enough. Recommended only if the person has cirrhosis and cannot have interferon. Genotype 4, 5 or 6 Recommended only if the person has cirrhosis. Not recommended by NICE NICE technology appraisal guidance (Feb 2015)
  10. 10. NEUTRINO: SOFOSBUVIR + P/R FOR 12 WKS IN TREATMENT-NAIVE GT 1/4/5/6 HCV PATIENTS• Open-label, single-arm study of sofosbuvir 400 mg QD + P/R for 12 wks in treatment-naive patients with GT 1/4/5/6 HCV • 17% had cirrhosis; 89% had GT 1, 9% had GT 4, < 1% had GT 5, 2% had GT 6 HCV Lawitz E, et al. EASL 2013. Abstract 1411. Reproduced with permission. P/R: pegIFN alfa-2a 180 µg/wk + RBV 1000-1200 mg/day HCVRNA<LLOQ(%) 99 99 90100 80 60 40 20 0 Wk 4 EOT SVR12 321/325 326/327 295/327n/N =
  11. 11. SIDE EFFECTS OF PEGYLATED INTERFERON• Flu like symptoms • Headaches • Forgetfulness • Insomnia, mood swings, depression or exacerbation of pre-existing psychiatric disorders • Rash, dry skin, slow healing • Myalgia, arthralgia • Nausea and vomiting, weight loss, loss of appetite • Thyroid dysfunction • Neutropenia • Injection site reactions • Hair thinning MANY ANTIVIRAL TREATMENT REGIMES IN THE NEAR FUTURE WILL CONTAIN PEGYLATED INTERFERON BUT TREATMENT IS LIKELY TO BECOME PEG FREE EVENTUALLY
  12. 12. SIDE EFFECTS OF RIBAVIRIN • Anaemia • Dry cough and thick phlegm • Mood swings • Haemolytic anaemia • Teratogenicity – two forms of contraception needed during treatment and for six months post treatment MANY ANTIVIRAL TREATMENT REGIMES IN THE FUTURE WILL ALSO CONTAIN RIBAVIRIN BUT EVENTUALLY REGIMES MAY BECOME RIBAVIRIN FREE
  13. 13. >95% SVR Preclinical Phase I Phase II Phase III Filed Telaprevir (TVR) Boceprevir (BOC) Simeprevir (SMV) Faldaprevir (FDV) Asunaprevir (ASV) ABT450r Danoprevir (DNVr) Sovaprevir Vaniprevir Vedroprevir IDX320 MK5172 Neceprevir Ciluprevir Narlaprevir VX985 Sofosbuvir (SOF) Mericita- bine (MCB) VX135 BMS986094 IDX184 PSI938 Ombitasvir ABT072 Deleobuvir GS9669 Tegobuvir BMS791325 Setrobuvir Lomibuvir TMC647055 Daclatasvir (DCV) Dasabuvir Ledipasvir (LDV) GSK2336805 Samatasvir PPI668 PPI461 ACH2928 BMS824393 ACH3102 MK8742 GS5816 Alisporivir (ALV) SCY635 PEG-IFN λ Mira- virsen GS9620 BIT225 ITX5061 IDN6556 LDV SOF Coformulation Status 09/2014 (selection) Ombitasvir Dasabuvir ABT450r FDVDBV ASV DCV MK5172MK8742 GS9669 LDVSOF MCB DNVr ASV DCV BMS791325 THE TORNADO OF HCV DRUG DEVELOPMENT Graphic includes several investigational agents which are not approved for use in HCV by the EMA/FDA; P: pegylated interferon; R: ribavirin
  14. 14. HEP C DIRECT ACTING ANTIVIRALS (DAAS) • Is there a need for so many treatments? • How are physicians going to determine which regimen for which patient? Will interferon still be present? • 50% depression rate in our outreach population – Peg is known to cause exacerbations of neuro psychiatric Symptoms. Concept of Pegylated interferon intolerability or ineligibility • Will it just come down to cost? 1. NCT02133131 SMV + PR + SOF ± RBV + DCV ± RBV + samatasvir + RBV DCV + PR + SMV ± RBV + SOF ± RBV + ASV ± BMS-791325 3D ± RBV SOF + PR + SMV + RBV + DCV ± RBV + LDV ± RBV + MK-5172 + MK-87421 MK-5172 + MK-8742 ± RBV + SOF1
  15. 15. MEDICATIONS LICENSED AND GOING THROUGH NICE APPROVAL •Ledipasvir •Daklinza (Daclatasvir) •3D (viekirax and Exviera plus Ribavirin if indicated) •Harvoni (Sofosbuvir and Ledipasvir) •NICE are expected to approve treatment for cirrhotic patients as a priority
  16. 16. EXPANDED ACCESS PROGRAMME (EAP) • NHSE commissioned • 600 patients in the UK would receive pre-NICE access to 12 weeks of oral therapy with Sofosbuvir + Ledipasvir or Daclatasvir + Ribavirin • All applications went through an exceptions panel • Criteria for patients to receive antiviral therapy through the EAP: Evidence of decompensated cirrhosis with an episode of ascites, variceal bleeding or encephalopathy; Childs Pugh Score > 7 (not suitable for other types of therapy); Exceptional circumstances (at risk of death in the next twelve months) • ? patients with cirrhosis are now going to be treated with these medications pre-NICE • Abvie 3D now becoming available pre-NICE NHSE (2014) Interim Clinical Commissioning Statement: Sofosbuvir Daclatasvir/Ledipasvir +/- Ribavirin for defined patients with Hepatitis C
  17. 17. Antiviral Therapy Outreach Service for HCV infected patients Rebecca Hawley Viral Hepatitis CNS, Kings College Hospital. March 2015
  18. 18. NATURAL HISTORY OF HCV INFECTION Exposure (Acute phase) ResolvedResolved Chronic CirrhosisStableStable SlowlySlowly ProgressiveProgressive HCC Transplant Death 20% (17) 15% (15) 85% (85) 25% (4) 80% (68) 75% (13) HIV andHIV and AlcoholAlcohol Alter MJ Semin Liver Dis 1995; 15: Management of Hepatitis C NIH Consensus Statement 1997; March 24-26:15(3).
  19. 19. HOW MANY PEOPLE ARE INFECTED WITH HCV IN LAMBETH? All persons aged 15-59 Estimated HCV positive Prevalence Estimated HCV- G1 (50% of HCV positive3 ) London 5,114,500 57,875 1.13% 28,938 Lambeth 205,500 3,154 1.53% 1,577 Health Protection Agency. Commissioning template for estimating HCV prevalence by DAT and numbers eligible for treatment. 2011 (Courtesy of Janssen non-promotional team)
  20. 20. APPLYING LAMBETH HCV ESTIMATES TO A NATURAL HISTORY MODEL Exposure (Acute phase) ResolvedResolved Chronic 3154 Cirrhosis StableStable SlowlySlowly ProgressiveProgressive HCC Transplant Death 20% (631) 15% 85% 25% (158) (80% 2523) 75% (473) HIV andHIV and AlcoholAlcohol AS MANY AS 631 PEOPLE IN LAMBETH COULD HAVE HCV RELATED CIRRHOSIS WITH 158 OF THOSE WITH END STAGE DISEASE OR HCC Alter MJ Semin Liver Dis 1995; 15: Management of Hepatitis C NIH Consensus Statement 1997; March 24-26:15(3) HCV - 85% chronicity rate with 20% cirrhosis rate1 and 3-5% risk per annum HCC2
  21. 21. OVERVIEW OF THE OUTREACH SERVICE • A collaboration between Kings College Hospital Viral Hepatitis Service (VHS) and South London and Maudsley (SLAM) - Lambeth • 2 year pilot commenced July 2011, finished September 2013 • Outreach Nurse based at Lorraine Hewitt House and a second treatment site was added at Paxton Green later in the project • Some RIOTT patients treated at Marina House (Southwark additionally) • New outreach service has commenced March 2015 – a further one year pilot across Lambeth and Southwark
  22. 22. 68 assessed for treatment 33 started Peg/Rib 3 TPV/Peg/Rib 1 self ceased 2 completed SVR1 CT with SIM or TPV + Peg/Rib completed SVR 23 completed 4 responder relapser 1 NR retreated TPV/Peg/Rib completed SVR 1 retreated completed TPV/Peg/Rib SVR 1 ongoing 19 SVR* 29 patients have completed treatment (2 patients retreated) 25 patients have achieved SVR, there were 3 Resp/Relapsers and 1 on Rx going Updated treatment summary 1 started TPV/Peg/Rib and was then referred to outreach to complete SVR
  23. 23. OVERALL SVR RATES PEG/RIB COMPLETED (N=23) G1 G2 G3 0 20 40 60 80 100 120 111 /1 14/16 4/6
  24. 24. OUTCOME • 39 clients started on treatment • 29 clients completed treatment, 23 were cured • 75% success rate on clients completing treatment
  25. 25. TRADITIONAL REFERRAL • All secondary care referrals to Dr Kosh Agarwal, Lead Consultant for Viral Hepatitis and Transplant Physician at KCH • All secondary care referrals triaged to multi-disciplinary clinic or nurse led pre-diagnostics which has an increasing role
  26. 26. OUTREACH 2015 • LJWG concensus statement (2014) – drug and alcohol use should not be a barrier to treatment for patients with HCV • Outreach service re started in March 2015 across Lambeth and Southwark; a collaboration between KCH viral hepatitis service and SLAM addiction services • Key workers are gate keepers to the service and play a vital role. • Teaching session in each clinic were provided to those who wanted to attend • Two raising awareness session in each area for clients
  27. 27. OUTREACH REFERRAL GUIDELINES • Referral for treatment should be considered when clients: • Want to engage with us and pursue treatment • Alcohol intake does not exceed 40 units a week* • Are stable in their drug use • Are housed or in a hostel (not sleeping rough) • Are willing to be adherent to medication regimes and attend appointments *Alcohol is known to progress fibrosis and impact on treatment response, all harm reduction measures should be in place to support and optimise clients pre-treatment
  28. 28. OUTREACH REFERRAL PATHWAY • Patient is referred via form following discussion with outreach CNS • Blood test appointment, fibro scan and AUS at KCH • Assessment with Nurses and discussion of treatment options • Hepatology triage and MDM discussion (teleconference from LHH) • 4 outcomes: 1. Refer back to drug and alcohol service or review in 6 months, 2. start treatment, 3. KCH for clinical trials, 4. KCH for expanded access programmes.