Hepatitis C: Increasing Access and Improving Cure Rates

Transcription

1 Hepatitis C: Increasing Access and Improving Cure Rates David Hachey, Pharm.D., AAHIVP Professor Idaho State University Department of Family Medicine Disclosures The planners and presenter have disclosed no conflict of interest, including no relevant financial relationships with any commercial interests pertaining to this activity. 1 Learning Objectives Pharmacists and Prescribers Describe the etiology, epidemiology and pathology of hepatitis C Explain current screening guidelines and testing methods for hepatitis C Rank patient attributes that qualify them as an appropriate treatment candidate Compare and contrast different drug classes available for the treatment of hepatitis C Learning Objectives Nurses and Pharmacy Technicians List the brand and generic names of two Hepatitis C medications Describe treatment goals of hepatitis C Identify solutions to high copays and rejected insurance claims for hepatitis C medications 3 4 ARS Question Current treatments can cure % of patients with hepatitis C if the are adherent. 50% 75% 90% 0% as hepatitis C is uncureable HCV ETIOLOGY, EPIDEMIOLOGY AND PATHOLOGY 6 1

2 HCV Patient Case Jane is a 55 year old, privately insured female, who has been filling prescriptions with your pharmacy for the past five years. Her past medical history and medications include GERD omeprazole 40 mg once daily HTN losartan / HCTZ 100 / 12.5 mg once daily DM type 2 metformin 1000 mg twice daily Depression escitalopram 20 mg once daily Social history married, 2 children, occasional alcohol use and ½ PPD smoker for 30 years, snorted cocaine in the 1980s a few times ARS Question Why should Jane be screened for hepatitis C? History of intranasal cocaine use History of alcohol use Her age She should not be screened for hepatitis C 7 Viral Hepatitis (Historical Perspective) Hepatitis Overview Viral hepatitis Infectious A NANB E Enterically transmitted Definition A systemic viral infection primarily causing liver inflammation Several clinical forms characterized by duration and severity Serum B D C F, G,? other Parenterally transmitted Epidemiology NHANES Survey: United States, and Prevalence of HCV Antibody, by Year of Birth Previously Non-A Non-B hepatitis (NANBH) Discovered as an independent virus in million living with chronic HCV (1.8% of the population) 20,000 new cases each year Incidence has declined by 80% in last 20years HCV Prevalence(%) Year of Birth Armstrong GL, et al. Ann Intern Med. 2006;144: National Health and Nutrition Examination Survey

3 Epidemiology Mortality Rates from Viral Disease Risk Factors Injection drug use Transfusion prior to 1992 Solid organ transplant MSM (men who have sex with men) Body tattoos Intranasal cocaine use HCV Pathology and Life Cycle Natural History JAMA August 13, 2014 Volume 312, No 6 15 Patient Case HCV SCREENING AND TREATMENT EVALUATION Jane returns to the pharmacy informing you her provider screened her for hepatitis C and that she was positive for hepatitis C. Confirmation testing was done and she said she had 10 million copies of virus and she was type 1. She is very distraught and concerned about her new diagnosis

4 ARS Question Steps in the HCV Care Continuum What would be the most appropriate counseling points for Jane? Maintain a healthy lifestyle as she will have it forever Use condoms when having sex as not to transmit it Discuss treatment options to cure the virus Discuss treatment options to chronically suppress the virus 19 Screening Diagnostic Testing Age Based Screening One-time HCV testing is recommended for persons born between 1945 and 1965, without prior ascertainment of risk. Risk behaviors Injection-drug use (current or ever, including those who injected once) Intranasal illicit drug use Other HIV infection Unexplained chronic liver disease and chronic hepatitis including elevated alanine aminotransferase levels Diagnostic Testing Genotype HCV exists as one of six distinct genotypes with markedly different clinical characteristics, mostly with respect to treatment response rates. In the United States, HCV genotype 1 is most common, accounting for 74% of prevalent cases. Determining HCV genotype is extremely important, because response to anti-viral therapy is different among genotypes, and treatment protocols differ substantially You don t run a marathon off the couch PATIENT PREPARATION 4

5 Risk Reduction Evaluation Injection Drug Use Substance abuse treatment Use new clean needles Do not share and dispose of appropriately Sexual transmission Condom use Household transmission Mother to Child Role of medical provider Thorough physical exam Presence of significant comorbidities Psychiatric history Co-infection with other viruses Stage of liver disease / Assessment of liver fibrosis Vaccines for both HAV/HBV Laboratory Studies CBC CMP AST/ALT Bilirubin Albumin / INR Heppanel / HIV HCV RNA HCV Genotype Counseling Patients OTCs APAP safely use, but if cirrhotic limit to 2 gm/ 24 hours NSAIDs generally safe unless cirrhotic Iron avoid excessive iron as some patients can store it Vitamin D generally safe and many patients are deficient Substance abuse Alcohol gas on a fire Smoking controversial Marijuana can accelerate cirrhosis / avoid Preparation Goal of Therapy = cure Cure= no detectable virus 12 weeks after therapy has been stopped The goal of treatment of HCV-infected persons is to reduce allcause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologiccure as evidenced by an SVR. Pretreatment considerations Patients with anti-hcv and the presence of HCV RNA should be considered as potential candidates Cost of therapy and newer agents Sustained VirologicResponse (SVR) after End of Therapy Undetecta ble Post New End of 12 Weeks New SVR12 Sustained Virologic Response (SVR12) = Undetectable HCV RNA 12 Weeks Post 5

6 Patient Selection Preparation is recommended for all patients with chronic HCV infection, except those with short life expectancies owing to comorbid conditions. Immediate treatment is assigned the highest priority for those patients with advanced fibrosis, those with compensated cirrhosis, liver transplant recipients, and patients with severe extrahepatic hepatitis C. Based on available resources, immediate treatment should be prioritized as necessary so that patients at high risk for liverrelated complications are given high priority. Adequate psychosocial support and psychiatrically stable Drug/alcohol use addressed prior to starting Payer source identified Patient Factors Age, substance abuse, comorbidities, literacy Evidence of good adherence Adherence education, barrier reduction No baseline blood dyscrasias If HIV infected, HIV well controlled Drug interactions addressed and mitigated -report/when-and-whom-initiatehcv-therapy 31 Patient Case APPLICATION OF DRUG THERAPY IN THE TREATMENT OF HCV Over the next 6 months Jane eliminated her alcohol use and reduced smoking to 5 cigarettes per day. She has lost pounds and her BP and diabetes are well controlled. She has completed her hepatitis vaccine series and is preparing to be treated by her provider for hepatitis C with ledipasvir-sofosbuvir (Harvoni ), one tablet once daily for 12 weeks. ARS Question Milestones What drug-drug interactions need to be resolved before Jane starts her therapy? Discontinue metformin because of lactic acidosis Decrease/discontinue PPI Increase escitaloprambecause of drug induced depression Discontinue losartan/hctz because of hyperkalemia 6

7 Milestones Drug Targets for HCV No field of medicine and therapeutics has changed as rapidly as hepatitis C in our lifetime Targets for Direct Acting Antivirals NS3/4A protease inhibitors NS5A inhibitors NS5B polymerase inhibitors Nucleoside and non-nucleoside NS3/4A Protease Inhibitors MOA protease is involved in post-translation processing of HCV polyproteins High potency Variable efficacy among genotypes Newer agents are pan-genotypic Low barrier to resistance Variable pharmacokinetics NS5A Inhibitors MOA exact role of this enzyme is unclear High potency Pangenotypic Low barrier to resistance Low drug interactions QD dosing NS5B polymerase inhibitors MOA this enzyme is required for copying the HCV-RNA genome and transcribing the mrna Nucleos(t)ide Moderately high potency and consistent across genotypes High barrier to resistance Some interactions Non-nucleoside Variable among getotypes Low barrier to resistance Lots of different targets 7

8 Daclatasvir(Daklinza ) NS5A inhibitor approved 7/24/15 Indications in combination with sofosbuvirfor treatment of genotype 1, 2 or 3 RBV may be added in certain cases Length 12 or 24 weeks Standard = 60 mg once daily with or without food Strong CYP450 3A4 inhibitor = 30 mg QD Moderate CYP450 3A4 inducer = 90 mg QD Side effects are mild and consist of fatigue, headache, nausea and diarrhea 43 Elbasvir-Grazoprevir (Zepatier ) NS5A and NS3/4A Inhibitor approved 1/28/16 Indications treatment of genotype 1 or 4 RBV may be added in certain cases Length 12 weeks in most cases, may extend to 16 weeks Fixed-dose tablet once daily with or without food Side effects are mild and consist of fatigue, headache, nausea and diarrhea Drug interactionsmay occur with CYP450 inducers and inhibitors Ledipasvir-Sofosbuvir (Harvoni ) NS5A and NS5B Inhibitor Approved 10/10/14 Indications-Genotype 1 and 4 patients Length 8 or 12 weeks in treatment naïvepatients without cirrhosis 12 weeks in treatment experiencedpatients without cirrhosis 24 weeks in treatment experiencedcirrhotic patients One tablet once daily with or without food Side Effects Fatigue and headache Ledipasvir-Sofosbuvir (Harvoni ) NS5A and NS5B Inhibitor Approved 10/10/14 One tablet once daily with or without food Side Effects Fatigue and headache Drug interactions Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir. Coadministrationof omeprazole (20 mg once daily) simultaneouslywith ledipasvir/sofosbuvirdecreased ledipasvircmaxand AUC by 11% and 4%, increased sofosbuvircmaxby 12% and no effect on sofosbuvirauc. Omeprazole 20 mg or lower can be administered simultaneously with ledipasvir/sofosbuvirunder fasted conditions. 8

9 Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir (ViekiraPak ) NS5A, NS3/4A and NS5B inhibitors Approved 12/9/14 Indications- Genotype 1 Ribavirin may be added in certain cases Length 12 weeks for most patients, 24 weeks in treatment experienced cirrhotic patients Two tablets of the co-formulated ombitasvir-paritaprevir-ritonavir (12.5/75/50 mg) once daily plus one dasabuvirtablet (250 mg) twice daily, with food, but without regard to fat or calorie content. Side Effects Fatigue, weakness and headache Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir (Viekira Pak ) Approved 12/9/14 Pharmacokinetics Contains Ritanovir, a pharmacokinetic enhancer which inhibitscyp450 3A4 to increase levels of paritaprevir Ombitasvir/Paritaprevir/Ritonavir (Technivie ) NS5A and NS3/4A Inhibitors Approved 7/24/15 Indications treatment of genotype 4 WITH ribavirin Length 12 weeks two tablets taken orally once daily in the morning with a meal, but without regard to fat or calorie content Side effects are mild and consist of weakness, fatigue, and nausea Drug interactionsmany interactions with CYP450 3A4 substrates Sofosbuvir(Sovaldi) NS5B Inhibitor Approved 12/6/13 Indication / Length GT 1 with daclatasvir for 12 weeks GT 2 With ribavirin for 12 weeks GT 3 With ribavirin for 24 weeks OR with daclatasvir for 12 weeks One tablet once daily with or without food Side Effects Few to no side effects, but often used with ribavirin which accounts for the majority of side effect Drug Interactions SJW and rifmapin 9

10 Ribavirin Mechanism of action is not totally clear (4 theories) Indication Used in conjunction with other agents SOMETIMES Should NEVER be used alone <75 Kg -400 mg AM 600 PM >75 Kg 600 mg BID Side Effects Anemia Teratogenic effects Extremely long half life WAC for 12 Week Genotype 1 Naïve Daclatasivir (Daklinza ) $63,000 Elbasvir-Grazoprevir(Zepatier ) $55,000 Ledipasvir-Sofosbuvir (Harvoni ) $94,000 Omb-Par-Rit(Technivie ) $76,000 Omb-Par-Rit + Das (Viekira Pak ) $83,000 Sofosbuvir(Sovaldi ) $84,000 Ribavirin ~$700 Daklinza + Sovaldi +/- Ribavirin 12 weeks for non-cirrhotic 24 weeks if the patient is cirrhotic Harvoni 8 weeks for patients with viral load < 6,000, weeks for patients with viral load > 6,000,000 Viekira Pak With Ribavirin for genotype 1a Without Ribavirin for genotype 1b Zepatier No mutations 12 weeks With mutations 16 weeks WITH Ribavirin Genotype 2 Naïve Sovaldi + Ribavirin 12 weeks for non-cirrhotic 16 weeks for cirrhotic Daklinza + Sovaldi 12 weeks for non-cirrhotic patients unable to take ribavirin 24 weeks for cirrhotic patients unable to take ribavirin Genotype 3 Naïve Daklinza + Sovaldi For 12 weeks for non-cirrhotic patients Daklinza + Sovaldi + Ribavirin 24 weeks for cirrhotic patients 10

11 Genotype 4 Naïve Harvoni for 12 weeks Technivie + Ribavirin for 12 weeks Sovaldi + Ribavirin for 24 weeks Zepatier for 12 weeks Coming to a Shelf Near You! Broad spectrum / pan-genotypic One tablet once daily Few side effects Few drug interactions Near 100% cure rates cost? Monitoring / Outcomes Bottom Line When Dispensing HCV Meds Undetecta ble New End of Post 12 Weeks New SVR12 Sustained Virologic Response (SVR12) = Undetectable HCV RNA 12 Weeks Post Do you have the ability to access the medications Are all of them being dispensed at once? How long is the patient being treated for? Does the patient have the ability to pay for the medications? Ensure the patient is getting the refills Two way education with the patient Summary Resources Healthcare providers understanding risk and pathologycan translate into better recommendations for screening and patient education Pharmacists are uniquely placed to help prepare patients for treatment, including vaccine administration and risk reduction Pharmacists and technicians should be able to help increase access to medications, reducedrug interactions, and improve chances of cure Pharmacist Resources Hepatitis Web Study study/ UW Hepatitis C Online Course Drug-drug interactions Clinical Guidelines Patient Resources Hepatitis Education Project Needy Meds