1 / 46

Preparing for Direct Acting Antivirals (DAAs) in Practice—New Paradigms in the Management of HCV

Sherilyn C. Brinkley, MSN, CRNP Nurse Practitioner/Program Manager Infectious Disease Department Johns Hopkins University Baltimore, Maryland. Preparing for Direct Acting Antivirals (DAAs) in Practice—New Paradigms in the Management of HCV. HCV Standard of Care 2011.

savanna-angeloz
Download Presentation

Preparing for Direct Acting Antivirals (DAAs) in Practice—New Paradigms in the Management of HCV

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Sherilyn C. Brinkley, MSN, CRNP Nurse Practitioner/Program Manager Infectious Disease Department Johns Hopkins University Baltimore, Maryland Preparing for Direct Acting Antivirals (DAAs) in Practice—New Paradigms in the Management of HCV

  2. HCV Standard of Care 2011 Ghany MG, et al. Hepatology. 2009;49:1335-1374.

  3. Preparing for Anti-HCV Therapy

  4. Case Study—Carmen • Carmen is a 59-year-old female from Puerto Rico diagnosed with chronic HCV in 1999 after moving to the United States and starting job as medical assistant • Previously evaluated and treated by a gastroenterologist but fell out of care in 2004 • Reports taking peginterferon and ribavirin for 48 weeks leading to an undetectable viral load followed by relapse • She heard about new anti-HCV drugs with shorter duration and wants more information

  5. Who Is a Candidate for Anti-HCV Treatment with DAAs? • Adults with chronic HCV genotype-1 infection • Treatment-naive or prior relapsers or nonresponders • If cirrhotic, should be compensated • Ability to adhere to dosing (peginterferon, ribavirin, and protease inhibitor) and monitoring schedule The protease inhibitor is never used as monotherapy Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011.

  6. Who Is NOT a Treatment Candidate? • Contraindications to peginterferon/ribavirin apply • Planning for pregnancy or unwilling to use adequate contraception • Coadministration of contraindicated drugs • Highly dependent on CYP3A for clearance • Strongly induce CYP3A • Special populations where safety and efficacy not established • Organ transplant • End-stage liver disease • Coinfected with HIV or HBV • Pediatrics Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011.

  7. What Are Key Components of HCV Evaluation? • Basic lab tests • HCV RNA by PCR, genotype, complete metabolic panel, prothrombin time/international normalized ratio, thyroid stimulating hormone, pregnancy test • Liver histology assessment (as needed) • Liver biopsy • Fibrosis markers • Comorbid disease status • Gauge patient motivation to take anti-HCV therapy

  8. Carmen’s Laboratory Findings

  9. Carmen’s Comorbidities and Current Medications • Comorbidities • Hypertension • Coronary artery disease • Hyperlipidemia • Insomnia • Current medications • Simvastatin • Aspirin • Trazodone • Atenolol

  10. How Do You Prepare Patients for Therapy? • Educate about treatment regimens and potential side effects • Discuss adherence to medications, administration schedule, food requirements, monitoring schedule • Explain variable treatment durations and futility rules • Review current medications, herbal products, and supplements for drug interactions • Counsel regarding pregnancy risk and contraception

  11. How Do You Prepare Your Practice Setting for Integration of DAAs? • Ensure adequate appointment time for patient counseling • Limit number of patients starting treatment each week to avoid clinic volume overload • Use treatment initiation checklist • Use pocket guides for drug interactions, response-guided therapy, and futility rules • Delegate tasks to others when appropriate • Prior authorizations • Medication administration teaching • Specialty pharmacy services

  12. Carmen’s Follow-Up Appointment • Carmen presents to clinic to review labs and biopsy results • Decision is made to treat with peginterferon, ribavirin, and a protease inhibitor • Next steps • Discuss side effects and lessons learned from prior therapy • Review current medication list for drug-drug interactions and discuss plan for changes • Consult patient’s cardiologist regarding clearance for treatment and an alternative lipid-lowering agent

  13. Treatment Goals and Challenges

  14. Why Treat Chronic HCV? • Sustained virologic response (SVR) is achievable • SVR is associated with gradual regression of fibrosis • SVR is associated with lower risk of liver failure and hepatocellular carcinoma Pearlman BL, et al. Clin Infect Dis. 2011;52:889-900.

  15. What Are the Benefits of Using DAAs? 1. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 2. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 3. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. 4. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 5. Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. 6. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011. • Higher SVR rates observed across all patient groups1-4 • Previously untreated, relapsers, partial and null responders • Response-guided therapy allows for 24- or 28-week duration for most treatment-naive patients with rapid response5,6

  16. Protease Inhibitor Phase III Clinical Trials 1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 3. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 4. Sherman KE, et al. 61st AASLD; October 29-November 2, 2010; Boston, Mass. Abstract LB-2. 5. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.

  17. SPRINT-2—Boceprevir in Treatment-Naive Genotype-1 Patients Two cohorts: 1, nonblack; 2, black. Abbreviations: B, boceprevir 800 mg TID; P, peginterferon -2b 1.5 µg/kg/wk; R, ribavirin 600–1400 mg/d; RGT, response-guided therapy; TW, treatment week.Poordad F, et al. N Engl J Med. 2011;364:1195-1206.

  18. SPRINT-2—SVR by Cohort and Treatment Arm Poordad F, et al. N Engl J Med. 2011;364:1195-1206.

  19. RESPOND-2—Boceprevir in Genotype-1 Prior Nonresponders Abbreviations: B, boceprevir 800 mg TID; P, peginterferon -2b 1.5 µg/kg/wk; R, ribavirin 600–1400 mg/d; RGT, response-guided therapy; TW, treatment week.Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.

  20. RESPOND-2—SVR by Prior Response Abbreviations: B, boceprevir 800 mg TID; P, peginterferon -2b 1.5 µg/kg/wk; R, ribavirin 600–1400 mg/d; RGT, response-guided therapy. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217.

  21. ADVANCE—Telaprevir in Treatment-Naive Genotype-1 Patients Abbreviations: eRVR, extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12); P, peginterferon -2a 180 µg/wk; R, ribavirin 1000–1200 mg/d; T, telaprevir 750 mg q8h.Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.

  22. ADVANCE—SVR Rates Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416

  23. REALIZE—Telaprevir in Genotype-1 Prior Nonresponders Abbreviations: P, peginterferon -2a 180 µg/wk; R, ribavirin 1000–1200 mg/d; T, telaprevir 750 mg q8h.Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.

  24. REALIZE—SVR by Prior Response Abbreviations: LI, lead-in; P, peginterferon -2a 180 µg/wk; R, ribavirin 1000–1200 mg/d; T, telaprevir 750 mg q8h. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.

  25. What Are the Challenges of Triple Combination Therapy? • Increased complexity • Protease inhibitor dosed every 8 hours • Food requirements • High pill burden • More adverse effects • Frequent lab monitoring and clinic visits • Emergence of resistance-associated variants if SVR not achieved • Increased cost

  26. Using Response-Guided Therapy

  27. How Does Response-Guided Therapy Impact Treatment Duration? • Both boceprevir and telaprevir use a response-guided therapy approach • Allows on-treatment virologic response to dictate treatment duration among noncirrhotics • Early response is the goal and may allow for a shorter duration of therapy

  28. Boceprevir—Response-Guided Therapy For all patients: peginterferon/ribavirin only weeks 1 through 4, then add boceprevir Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011.

  29. Boceprevir—Additional Duration Instruction • Response-guided therapy was not studied in patients who did not achieve early virologic response (<2-log drop in HCV RNA by week 12) during prior therapy • These patients should receive 4 weeks of peginterferon/ribavirin followed by 44 weeks of triple therapy • For treatment-naive patients who have a poor response (<1-log drop in HCV RNA) to peginterferon/ribavirin after the 4-week lead-in phase, consider extending boceprevir in combination with peginterferon/ribavirin through week 48 Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011.

  30. Telaprevir—Response-Guided Therapy For all patients: telaprevir, peginterferon, and ribavirin start on day 1 Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.

  31. Should Response-Guided Therapy Be Used in Cirrhotics? • Boceprevir1 • Patients with compensated cirrhosis should receive 4 weeks of peginterferon alfa and ribavirin followed by 44 weeks of triple therapy • Telaprevir2 • Treatment-naive patients with cirrhosis who have undetectable HCV-RNA at weeks 4 and 12 of telaprevir combination treatment may benefit from an additional 36 weeks of peginterferon/ribavirin (48 weeks total) 1. Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. 2. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.

  32. What If a Patient Has a Poor Virologic Response? • Futility (stopping) rules are guidelines that require discontinuation of treatment medications at specific time points in the event of inadequate response • Stopping rules for futility • Decrease drug exposure • Minimize emergence of resistance • Lower cost

  33. Boceprevir—Futility (Stopping) Rules Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011.

  34. Telaprevir—Futility (Stopping) Rules Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.

  35. What Are the Implications of Inadequate Virologic Response? 1. Kieffer TL, et al. J Antimicrob Chemother. 2010;65:202-212. 2. Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. 3. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011. 4. Vierling JM, et al. 46th EASL; April 14-18, 2010; Berlin, Germany. Abstract 2016. 5. Sullivan JC, et al. 47th EASL; March 30-April 3, 2011; Barcelona, Spain. Abstract 8. • HCV has rapid viral dynamics and high mutation rate1 • Baseline resistance mutations exist • 7% of population in boceprevir trials2 • 5% of population in telaprevir trials3 • Some achieve SVR regardless2,3 • Majority of patients with protease inhibitor treatment failure are left with resistant variants2,3 • Predominant strain returns to wild type in majority within 2 years4,5 • Cross resistance with other protease inhibitors anticipated1 • Long-term clinical impact unknown

  36. Safety Considerations with DAAs

  37. Are There Drugs to Avoid with Protease Inhibitors? • Boceprevir and telaprevir are inhibitors of CYP3A1,2 • Use of boceprevir or telaprevir with drugs/herbs metabolized by CYP3A may lead to1,2 • Altered drug concentrations • Loss of therapeutic activity • Adverse events from toxicity • Refer to lists of contraindicated drugs and drugs to use with caution in FDA-approved product package inserts1,2 • Use drug-drug interaction pocket guide and refer to drug interaction websites • http://www.hep-druginteractions.org/ • Review patient medication/supplement list at each patient interaction 1. Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. 2. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011.

  38. Are There Additional Contraceptive Requirements with DAAs? Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011. • Ribavirin may cause birth defects and fetal death • Negative pregnancy test prior to therapy and monthly • 2 forms of contraception during therapy and for 6 months posttherapy • Systemic hormonal contraception should not be relied upon as effective method during protease inhibitor use • Decreased ethinyl estradiol concentrations • Use 2 effective nonhormonal methods of contraception (barrier methods or nonhormonal IUD)

  39. What Are the Most Common Side Effects with Protease Inhibitors? 1. Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. 2. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011. • Boceprevir (≥35% of subjects)1 • Fatigue, anemia, nausea, headache, dysgeusia • Telaprevir (≥5% higher than in controls)2 • Rash, pruritus, anemia, nausea, hemorrhoids, diarrhea, anorectal discomfort, dysgeusia, fatigue, vomiting, anal pruritus

  40. Anemia Management Is a Mainstay of Anti-HCV Therapy Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; 2011. • Increased anemia with boceprevir and telaprevir • Hematologic parameters at baseline and treatment weeks 2, 4, 8, 12, and periodically after–typically every 4 weeks–or more frequently as clinically indicated • Utilize anemia management tools employed with peginterferon and ribavirin • Ribavirin dose reduction • Erythropoietin • Never dose reduce protease inhibitor

  41. Adherence Equals Safety Adherence with medication regimen is critical but only part of the story

  42. Carmen’s Pretreatment Counseling • Select medication dosing schedule every 7−9 hours for protease inhibitor • Customize written daily schedule for taking ribavirin and protease inhibitor with detailed food requirements • Reinforce adherence with doses, labs, and clinic visits • Instruct to not take new medications, supplements, or herbals without provider clearance • Emphasize to never discontinue or dose reduce the protease inhibitor • Review side effects of protease inhibitor, peginterferon, and ribavirin

  43. Carmen’s Pretreatment Counseling • Discuss and document contraceptive plan • Postmenopausal • Vasectomy • Review response-guided therapy and potential treatment durations • Explain rationale for futility rules • Review clinic/provider contact information • Provide lab requisitions, lab schedule, next appointment reminder • Demonstrate peginterferon injection

  44. Carmen Begins Triple Therapy • She leaves with lab orders for end of treatment weeks 2 and 4 • She has a follow-up visit scheduled in 2 weeks • She will begin treatment the next day after breakfast • 1st telaprevir and ribavirin doses at 7:00 am • 1st peginterferon dose planned for 6:00 pm • She remembers the flu-like symptoms with peginterferon from prior therapy and plans to premedicate with ibuprofen • She will enlist the support of her family

  45. Summary • DAAs improve SVR rates among all genotype-1 patient groups • Triple therapy utilizes response-guided therapy and potential for shortened treatment duration • Anti-HCV treatment is increasingly complex with drug-drug interactions, increased pill burden and dosing frequency, risk of protease inhibitor resistance, and more side effects • Pretreatment education requires adequate time and detail to prepare patients for treatment success

  46. Thank you for your participation. To earn CME/CE credit, please complete the posttest and evaluation. (Click link in the navigation bar above or to the left of the slide presentation.) Your feedback is appreciated and will help us continue to provide you with clinically relevant educational activities that meet your specific needs.

More Related