Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Hcv presentation

1,638 views

Published on

Advances in HCV treatment

Published in: Health & Medicine
  • Be the first to comment

Hcv presentation

  1. 1. Advances in HCV TREATMENT DR. SADIQ ZIA
  2. 2. ALT DOES NOT MEAN ABSOLUTE LIVER TEST DR. SADIQ ZIA
  3. 3. AND
  4. 4. SGPT SHOULD NOT MEAN SIMPLE G.P. TEST
  5. 5. The primary goal of HCV treatment is viral eradication Primary objective  Viral eradication – SVR  Arrest progression of necrosis/fibrosis Secondary objective  Reduce progression of fibrosis/cirrhosis  Prevent decompensation  Prevent HCC SVR = sustained virological response HCC = hepatocellular carcinoma
  6. 6. HCV infection is considered eradicated when an SVR is achieved  SVR is defined as absence of HCV RNA in the serum at the end of treatment and 6 months later1  >99% of patients remained HCV RNA-negative after completion of treatment with pegylated interferon alfa- 2a (40KD) plus ribavirin when assessed for 3.9 years (range 0.8–7.1) from the last date of treatment • SVR is long lasting and clinical relapse is extremely rare in patients who are ‘cured’ of chronic hepatitis C 1. Ghany M, et al. Hepatology 2009; 49: 1335 2. Swain M, et al. Gastroenterology 2010; 139: 1593.
  7. 7. Response Definition RVR* HCV RNA negative (<50 IU/mL) at week 4 eRVR HCV RNA negative (<50 IU/mL) at week 4–24 EVR** Complete EVR HCV RNA positive at week 4 but negative at week 12 Partial EVR HCV RNA positive at week 4 and 12 but ≥2 log10 drop from baseline at week 12 Non-EVR <2 log10 drop from baseline at week 12 Definitions of on-treatment response * RVR = rapid virological response ** EVR = early virological response
  8. 8. Patterns of virological response Sustained responder (SVR) Null responder Baseline Treatment Time Relapser Partial responder Undetectable HCV RNA HCVRNA Breakthrough Detection limit 6 months 1. Ghany M, et al. Hepatology 2009; 49: 1335 2. Farci P, et al. Proc Natl Acad Sci U S A 2002; 99: 3081
  9. 9. Treatment failure: definitions Non-response • Detectable HCV RNA levels at the end of treatment or end of follow-up. Includes: – Null responders: failure to decrease HCV RNA by at least 2 logs after 24 weeks – Partial responders: ≥2 log decrease in HCV RNA but positive at week 24 – Relapsers: HCV RNA-negative at the end of treatment but subsequently positive during the follow-up period Breakthrough • HCV RNA levels become undetectable during treatment, but virus reappears while still on treatment Ghany M, et al. Hepatology 2009; 49: 1335
  10. 10. Biochemical and histological responses: definitions Biochemical response • Normalisation of serum alanine aminotransferase (ALT) levels1 (if elevated at baseline) Histological response • Improvement of ≥2 points in total Histology Activity Index (HAI) score at the end of follow-up (24 weeks post-treatment), using the Knodell scoring system2 1. Perry C, Jarvis B. Drugs 2001; 61: 2263 2. Heathcote E, et al. N Engl J Med 2000; 343: 1673
  11. 11. Probability of SVR Interactions of Multiple Factors Cirrhosis No No No No No No No Yes ALT quotient 7 2 2 2 2 2 1 1 Age (years) 20 20 43 43 43 60 60 60 BMI (kg/m2 ) 20 20 26 26 26 30 30 30 HCV RNA (IU/mL ×103 ) 40 40 40 1200 9000 9000 9000 9000 ProbabilityofAchievinga SustainedVirologicResponse 97 89 74 52 36 19 14 7 0 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8Patient Number Foster GR et al. Scand J Gastroenterol. 2007;42:247-255.
  12. 12. Evolution of hepatitis C treatment Discovery of HCV genome Addition of RBV to IFN alfa improved outcomes Peg-IFN alfa plus RBV becomes gold standard Treatment with IFN alfa for 24 or 48 weeks – 3x weekly dosing – Poor outcomes Peg-IFN mono – once-weekly dosing 20101989 Response-guided therapy emerging New antivirals enter development
  13. 13. HCV treatment Pegylated interferon plus ribavirin is the current gold standard
  14. 14. Pegylated interferons lead to a significantly better treatment outcome 6% 13% 41% 66% 0 10 20 30 40 50 60 70 IFN 24 weeks1 IFN 48 weeks1 IFN+RBV 48 weeks1,2 PEGASYS® + COPEGUS® 48 weeks3 SVR(%) 1. McHutchison J, et al. N Engl J Med 1998; 339: 1485 2. Poynard T, et al. Lancet 1998; 352: 1426 3. Zeuzem S, et al. J Hepatol 2005; 43: 250 1998 2004
  15. 15. Approved treatment duration is 48 weeks for genotype 1* and 24 weeks for genotype 2/3 84% 79% 0 20 40 60 SVR(%) Genotype 1 80 81% 80% 100 Genotype 2/3 24-LD 24-SD 48-LD 48-SD 96 144 99 153 Hadziyannis S, et al. Ann Intern Med 2004; 140: 346 PEGASYS® 180 µg plus COPEGUS® 29% 41%42% 52% n= 101 118 250 271 LD = RBV 800 mg/day; SD = RBV 1000–1200 mg/day * 24 weeks may now be considered for patients with a low viral load (≤800 000 IU/mL) at baseline and who achieve an RVR (EU only)
  16. 16. Treatment of Chronic Hepatitis C with Peginterferon and Ribavirin SVR Rates in Pivotal Trials Pegasys1,2 PEG-Intron3 Overall 56% & 63% 54% (61%) Genotype 1 46% & 52% 42% (48%) Genotype 1, HVL 41% & 47% 30% (37%) Genotype 2 & 3 76% & 84% 1 Fried MW, et al. N Engl J Med 2002;347:975-982. 2 Hadziyannis S, et al. Ann Intern Med 2004;140:346-355. 3 Manns MP, et al. Lancet 2001;358:958-965. (RBV > 10.6 mg/kg by post-hoc analysis)
  17. 17. Side Effects of PegIFN/Ribavirin • Depression ranging from mild to suicidality • Irritability, aggressive behavior • Worsening of mania • Fatigue • Insomnia • Myalgias, fever, flu- like symptoms • Hair loss • Cytopenias“Interferon Man” Slide courtesy Chia Wang
  18. 18. To Treat or not to Treat: A Constellation of Considerations Duration of infection Personal plans (marriage, pregnancy) Age ALT HIV coinfection Extrahepatic Features (Fatigue, EMC, PCT) Patient "mindset" Genotype virus Genotype Patient (IL28) Contraindications & comorbidities Insulin Resistance Histologic stage 20%+ life time risk Of cirrhosis Family and other support Occupation PinK AALSD CME 2009
  19. 19. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C Evolution of HCV Therapy 2001 PegIFN/RBV
  20. 20. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C Evolution of HCV Therapy 2001 2011 PegIFN/RBV Protease inhibitor
  21. 21. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C Evolution of HCV Therapy 2001 2011 Beyond PegIFN/RBV Protease inhibitor Nucleos(t)ide polymerase inhibitor Nonnucleoside polymerase inhibitor NS5A inhibitor
  22. 22. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C New Therapies  Nucleoside and nucleotide polymerase inhibitors  Non-nucleoside polymerase inhibitors  NS5a inhibitors  Novel Interferons  Other Immune Modulators  Anti-fibrotics
  23. 23. Role of Genes
  24. 24. SOME OF THE NEW NAMES YOU WOULD COME ACROSS SOON BOCEPRAVIR TELEPRAVIR Vaniprevir Danoprevir Filibuvir Narlaprevir
  25. 25. THANKS
  26. 26. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C Oral drugs (known as direct-acting antivirals, or DAAs) that specifically target certain steps in the hepatitis C virus life cycle are in late-stage development. New Therapies
  27. 27. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C HCV Life Cycle and DAA Targets Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000. Receptor binding and endocytosis Fusion and uncoating Transport and release (+) RNA Translation and polyprotein processing RNA replication Virion assembly Membranous web ER lumen LD LD ER lumen LD NS3/4 protease inhibitors NS5B polymerase inhibitors Nucleoside/nucleotide Nonnucleoside *Role in HCV life cycle not well defined NS5A* inhibitors
  28. 28. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C  HCV-specific protease inhibitors will be the first DAA class available. – Protease inhibitors block cleaving of viral proteins New Therapies
  29. 29. clinicaloptions.com/hepatitis Change Folio Title on Master /Arial 15pt /Unbold White clinicaloptions.com/hepatitis Future Generations: Direct-Acting Antivirals for Hepatitis C Select DAAs in Clinical Development Phase I Phase II Phase III Protease Inhibitors ABT-450 ACH-1625 GS 9451 MK-5172 VX-985 BMS-650032 CTS-1027 Danoprevir GS 9256 IDX320 Vaniprevir BI 201335 Boceprevir Telaprevir TMC435 Nonnucleoside polymerase inhibitors BI 207127 IDX375 ABT-333 ABT-072 ANA598 BMS-791325 Filibuvir Tegobuvir VX-759 VX-222 Nucleoside polymerase inhibitors IDX184 PSI-7977 RG7128 NS5A inhibitors A-831 PPI-461 BMS-790052 BMS-824393 CF102
  30. 30. PEGASYS® plus COPEGUS® : SVR rates of up to of 61% in genotype 1 0 10 20 30 40 50 60 70 80 SVR(%) 60% 46% 52% 52% 2005 Zeuzem5 2002 2004 298 271 95 90 Fried2 Hadziyannis3 2006 Ferenci4 1. Manns M, et al. Lancet 2001; 358: 958 2. Fried M, et al. N Engl J Med 2002; 347: 975 3. Hadziyannis S, et al. Ann Intern Med 2004; 140: 346 4. Ferenci P, et al. J Hepatol 2006; 44: 275 5. Zeuzem S, et al. J Hepatol 2005; 43: 250; 6. Sakai T, et al. EASL 2006; Abstract 605 n= 99 61% 2006 Sakai6 0 10 20 30 40 50 60 70 80 SVR(%) 42% 348 2001 Manns1 n= Peg-IFNα-2b (12KD) + RBV PEGASYS® + COPEGUS® 48-week treatment duration
  31. 31. PEGASYS® plus COPEGUS® : SVR rate of >90% in genotype 2/3 *Patients had undetectable HCV RNA at Week 4 1. Hadziyannis S, et al. Ann Intern Med 2004; 140: 346 2. Von Wagner M, et al. Gastroenterology 2005; 129: 522 3. Yu M-L, et al. Gut 2007; 56: 553 4. Zeuzem S, et al. J Hepatol 2004; 40: 993 5. Mangia A, et al. N Engl J Med 2005; 352: 2609 Von Wagner*2 84% 80% n=0 10 20 30 40 50 60 70 100 90 80 SVR(%) 20042004 Hadziyannis1 2006 Yu3 95% 96 71 100 Peg-IFNα-2b (12KD) + RBV PEGASYS® + COPEGUS® 24-week treatment duration 81% 76% n=0 10 20 30 40 50 60 70 100 90 80 SVR(%) 2004 2005 Mangia5 Zeuzem4 224 70
  32. 32. Safety/tolerability
  33. 33. Management of patients treated with interferon plus ribavirin  Monitoring and dose reduction for ribavirin-related anaemia  Monthly monitoring for pregnancy; emphasis on prevention  Monitoring white blood cell and platelet counts  Monitoring for evidence of depression REBETRON™. PDR®
  34. 34. Safety/tolerability  Compared with conventional combination therapy, fewer patients receiving PEGASYS® plus COPEGUS® report ’flu-like symptoms such as pyrexia, myalgia and rigors  The incidence of depression is significantly lower among patients receiving PEGASYS® plus COPEGUS® than among those receiving conventional combination therapy (22% versus 30%; p=0.01)  Better tolerability should encourage better patient adherence Fried M, et al. N Engl J Med 2002: 347: 975 Conventional combination therapy refers to interferon alfa plus ribavirin
  35. 35. The role of ribavirin
  36. 36. Ribavirin is a critical component of HCV therapy  Pegylated interferon plus ribavirin is the current standard of care for the treatment of chronic hepatitis C  Ribavirin plays an important role in combination with pegylated interferon but what is it and how does it work?
  37. 37. Ribavirin: exact MOA not fully understood  Potential mechanisms for antiviral activity of ribavirin:1 • Direct inhibition of HCV replication • Inhibition of the enzyme inosine-monophosphate- dehydrogenase (IMPDH) • Immunomodulation • Mutagenesis  Ribavirin plays an important role in combination with pegylated interferon during all stages of HCV therapy 1. Dixit N & Perleson A, Cell Mol Life Sci 2006; 63: 832
  38. 38. Significantly faster viral decay with addition of ribavirin 6 Viralload(log10IU/mL) 5 4 3 2 1 0 7 14 21 28 42 Limit of detection PEGASYS® 180µg/wk plus COPEGUS® 1000–1200 mg/day (n=10) PEGASYS® 180µg/wk (n=17) 56 Days Herrmann E, et al. Hepatology 2003; 37: 1351
  39. 39. Increase in SVR by prevention of relapse with addition of ribavirin Patients(%) 56% 29% Fried M, et al. NEJM 2002; 347: 975 0 10 20 30 40 50 60 70 80 90 100 n= 224 453 224 453 132 313 SVR Relapse PEGASYS® 180 µg/wk + COPEGUS® 1000–1200 mg/day PEGASYS® 180 µg/wk 51% 19% 48 weeks’ treatment; all patients 69% 59% ETR ETR = end-of-treatment response
  40. 40. Maintaining ribavirin exposure prevents breakthrough* and relapse 0 10 20 30 40 50 PEGASYS® 180 µg/wk plus COPEGUS® 800 mg/day PEGASYS® 180 µg/wk 30 36 48 Bronowicki J-P, et al. Gastroenterology 2006; 131: 1040 2% 5% 2% 6% 12% p=0.010 52 60 72 14% 32% 26% 42% 29% 42% p<0.001 p=0.004 p=0.020 Week DetectableHCVRNA(%) 3% * Defined as achievement of HCV RNA negativity during treatment but becoming positive again before the end of treatment
  41. 41. Treatment intensification in difficult-to-cure patients
  42. 42. A number of factors influence response to therapy Host factors • Race • Age • Gender • Body weight* • Insulin resistance* • Substance abuse* • Comorbidities* Treatment • Adherence* • Side effects* • Type of regimen* • Dose* • Duration* • Experience of MD* Viral factors • Genotype • Viral load Disease factors • Coinfection* • Fibrosis • Cirrhosis Reasons for treatment failure * Factors which can be influenced
  43. 43. Genotype is the most important baseline predictor of response 1. Lee S, et al. J Hepatol 2002; 37: 500 2. Roche data on file 0 20 40 60 80 100 120 140 160 180 G enotype (1 versus non-1) Pre-treatm entviralload AgeALT quotient H istology R ace B ody w eight 800 versus 1000 or 1200 m g C O PEG U S® U S vs non-U S G ender WaldChi-square Patients treated with PEGASYS®
  44. 44. Treatment intensification Treatment intensification Increase COPEGUS® dose Increase PEGASYS® dose PEGASYS® 270 µg/wk + COPEGUS® for 48 weeks Fixed-dose induction: PEGASYS® 360 µg/wk + COPEGUS® for 12 weeks followed by 180 µg/wk + COPEGUS® for 36 weeks Increase PEGASYS® + COPEGUS® treatment duration (Response-guided therapy) PROGRESS G1 HVL pilot study G1 HVL pilot study PROGRESS
  45. 45. Re-treatment of previous non-responders and relapsers: maximising success with PEGASYS® plus COPEGUS®
  46. 46. Introduction  There is a large and growing number of patients not achieving a sustained virological response (SVR) with the current standard of care  Effective treatment strategies for these patients are needed today 1. Ghany M, et al. Hepatology 2009; 49: 1335 2. Dienstag J & McHutchison J. Gastroenterology 2006; 130: 225
  47. 47. 1. Manns M, et al. Lancet 2001; 358: 958; 2. Fried M, et al. N Engl J Med 2002; 347: 975 3. Hadziyannis S, et al. Ann Intern Med 2004; 140: 346 4. Zeuzem S, et al. J Hepatol 2005; 43: 250 SVR rates increase over time but 30–50% of patients do not achieve SVR 2002 2004 2005 511 453 436 134 Fried2 Hadziyannis3 Zeuzem4 56% 63% 66% 54% 2001 Manns1 Peg-IFNα-2b (12KD) + RBV PEGASYS® + COPEGUS®48-week treatment duration n= 0 10 20 30 40 50 60 70 100 90 80 SVR(%) All genotypes
  48. 48. Definition of non-response and relapse  Non-response: occurs when a positive serum HCV RNA test result is observed at every assessment after initiation of treatment  Relapse: occurs if HCV RNA falls below the limit of detection (<50 IU/mL) during treatment but becomes detectable after end of treatment • If relapse occurs before the treatment regimen is complete this is termed virological breakthrough 1. Jensen D, et al. Ann Intern Med 2009; 150: 528 2. Ghany M, et al. Hepatology 2009; 49: 1335 3. Farci P, et al. PNAS 2002; 99: 3081
  49. 49. PEGASYS® is indicated for re-treatment of treatment-experienced patients  PEGASYS® plus RBV is indicated for patients who have failed previous treatment with IFN alpha (pegylated or non-pegylated) alone or in combination with RBV • Recommended treatment duration is 48 weeks – 72 weeks for genotype 1 PegIFN/RBV non-responders • Patients who have detectable virus at week 12 should stop therapy PEGASYS® SPC, October 2009
  50. 50. Re-treatment of relapsers: the Kaiser study
  51. 51. Kaiser study: summary  SVR rate of 50% achieved with 72 weeks of re-treatment with PEGASYS® in patients who had previously relapsed  Achieving an RVR or negative HCV-RNA at week 12 of therapy is highly predictive of achieving SVR  A 72 week re-treatment regimen was well tolerated in these relapser patients  Based on these data an extended 72 week treatment duration for relapsers should be considered Kaiser S, et al. Hepatology 2008; 48 (4, Suppl); 1140A
  52. 52. Other patient populations
  53. 53. Patients with cirrhosis
  54. 54. Higher SVR rates are achieved in patients without cirrhosis Bruno S, et al. Hepatology 2009; 51: 388 Patients without bridging fibrosis/cirrhosis Patients with bridging fibrosis Patients with cirrhosis Genotype 2/3 24 weeks† n= 60 51 33 242 63 36 76 61 57 629 119 70 * 48 weeks PEGASYS® 180 µg/wk plus COPEGUS® 1000/1200 mg/day † 24 weeks PEGASYS® 180 µg/wk plus COPEGUS® 800 mg/day Trend test: p=0.0028 (Genotype1/4) and p=0.0001 (Genotype 2/3) Genotype 1/4 48 weeks* SVR(%) 0 40 60 80 20
  55. 55. PEGASYS® + COPEGUS® : improved efficacy in cirrhotic patients Fried M, et al. N Engl J Med 2002; 347: 975 IFN alfa-2b + ribavirin 0 10 20 30 40 33% 50 n=54 SVR(%) PEGASYS® plus COPEGUS® 0 10 20 30 40 43% 50 n=56 SVR(%)
  56. 56. Chronic hepatitis C and ‘normal’ alanine aminotransferase (ALT) levels
  57. 57. Chronic hepatitis C and alanine aminotransferase (ALT)  Up to 46% of patients with chronic hepatitis C have ALT levels within the currently defined ‘normal’ range1  These patients were historically considered ‘healthy’ or ‘asymptomatic’ and have not received treatment  However, >80% have some degree of liver damage on biopsy2  Quality of life is significantly impaired in patients with chronic hepatitis C (and elevated or persistently ‘normal’ ALT)3 1. Alberti A, et al. Ann Intern Med 2002; 137: 961 2. Puoti C, et al. J Hepatol 2002; 37: 117 3. Foster G, et al. Hepatology 1998; 27: 209
  58. 58. ALT levels do not always correlate with degree or severity of liver disease  Although elevated ALT levels are generally associated with hepatocellular damage, lower levels are not always associated with mild liver disease  ALT levels fall as cirrhosis develops  Many factors, independent of liver damage, can affect ALT levels  ALT levels may fluctuate throughout the course of chronic hepatitis C
  59. 59. A single ALT value may not be representative of the true ALT status  It is recommended that ALT status be defined by three measurements over a 6-month period1  However, studies suggest that this time period may not be adequate2  Patients with ALT levels within the ‘normal’ range may show further reduction in serum ALT levels following treatment3 1. Marcellin P, et al. Hepatology 1997; 26: 133S 2. Puoti C, et al. J Hepatol 2002; 37: 117 3. Di Bisceglie A, et al. Hepatology. 2001; 33: 704
  60. 60. 77% of patients with ‘normal’ ALT have some degree of liver damage ‘Normal’ ALT Shiffman M, et al. J Infect Dis 2000; 182: 15 Elevated ALT No Fibrosis 23% Mild 39% Portal 26% Bridging 6% Cirrhosis 6% No Fibrosis 19% Mild 19% Cirrhosis 22% Bridging 16% Portal 24%
  61. 61. Fibrosis progression occurs in patients with ‘normal’ ALT 2 4 6 8 10 12 Years 0 20 40 60 80 100 Cumulativeprobabilityoffibrosis(%) ‘Normal’ ALT Elevated ALT p=0.06 Hui C-K, et al. J Hepatol 2003; 38: 511
  62. 62. PEGASYS® plus COPEGUS® in patients with ‘normal’ ALT levels  In chronic hepatitis C patients with elevated ALT levels • PEGASYS® plus COPEGUS® therapy shows significant improvement in efficacy and tolerability over conventional interferon-based therapy across all HCV genotypes, irrespective of viral load1  PEGASYS® is the first and only pegylated interferon approved in the European Union for the treatment of patients with ALT levels persistently within the current ‘normal’ range 1. Fried M, et al. N Engl J Med 2002; 347: 975
  63. 63. Treatment and ALT levels  AASLD 2009 guidelines state: • Regardless of the serum ALT level, the decision to initiate therapy with pegylated interferon and ribavirin should be individualized based on the severity of liver disease by liver biopsy, the potential for serious side effects, the likelihood of response, and the presence of comorbid conditions Ghany MG, et al. Hepatology 2009; 49: 1335
  64. 64. Children and adolescents
  65. 65. Chronic hepatitis C in children and adolescents  The prevalence of HCV in children is approximately: • 0.2% in those younger than 12 years old1 • 0.4% in those between 12 and 19 years old1  The main route of transmission of HCV in children is blood transfusion2  Of those infected, 30-60% will develop chronic HCV infection1  Children with HCV respond better to IFN than adults: • Sustained response rates in patients with HCV genotype 1 infection: 27% vs. 8–10% for children and adults respectively3 1. Mushtaq M et al. Curr Pediatr Res 2009; 13 (1 & 2): 35 2. El-Raziky MS et al. World J Gastroenterol 2007; 13(12): 1828 3. Jacobson IM et al. J Pediatr Gastroenterol Nutr. 2002 Jan; 34(1): 52
  66. 66. 57% 57% Genotype 2/3 (24 weeks) Genotype 1/4/5/6 (48 weeks) Sokal EM, et al. J Hepatol 2010; 52: 827 Early response (12 weeks) EOT SVR 83% 15/18 27/47 94% 17/18 27/47 89% 57% 16/18 27/47n/N CHIPS: virological response in children and adolescents with PEGASYS® plus COPEGUS® Virologicalresponserate(%) 60 0 40 80 100 20
  67. 67. CHIPS: PEGASYS® plus COPEGUS® was generally well tolerated in children and adolescents Sokal EM, et al. J Hepatol 2010; 52: 827 *Includes fever † Includes irritability, depression and change of mood N number shown at the bottom of each bar Flu-like sym ptom s*H eadache Abdom inalpain FatiguePsychiatricD erm atitis N ausea/vom iting D ecreased appetiteInsom niaSore throatD iarrhoea Injection site reactions B acterialinfectionsB reathless Thyroid problem Incidence(%) 54 45 38 34 34 29 23 22 18 15 14 14 14 11 11 222935 1215 925 22 1419 10 7 799 30 0 20 50 60 10 40

×