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Curing Chronic Hepatitis C: a Cost Comparison of the Combination Simeprevir Plus Sofosbuvir Vs

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366 Langness JA, et al. , 2017; 16 (3): 366-374 ORIGINAL ARTICLE May-June, Vol. 16 No. 3, 2017: 366-374 The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy Jacob A. Langness,*,† David Tabano,† Amanda Wieland,‡ Sarah Tise,‡ Lindsay Pratt,‡ Lauren Ayres Harrington,§ Sonia Lin,* Vahram Ghuschcyan,†,|| Kavita V. Nair,† Gregory T. Everson§ * Department of Pharmacy, University Of Colorado Hospital, Aurora, CO, USA. † Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. ‡ University of Colorado Denver, Department of Medicine, Division of Gastroenterology and Hepatology, Aurora, CO, USA. § University of Colorado Denver, School of Medicine, Aurora, CO, USA. || American University of Armenia, Yerevan, Armenia. ABSTRACT Introduction. Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effec- tive and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. Material and methods. Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population. The multi-DAA regimen of simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen consisting of peginterferon and ribavirin, with either boceprevir or telaprevir (TT). Sustained-virologic response (SVR) rates, total costs per treatment and adverse events were recorded. Total cost per SVR were compared for the two treatments, controlling for patient de- mographics and clinical characteristics. Results. One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n = 113). Patients receiving SMV/SOF were older, more treatment experienced, and had a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per patient were $152,775 and $95,943, and average total costs per SVR were $178,237 vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs accounted for 98% of SMV/SOF and 85% of TT treatment costs. Conclusion. The high cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs, such that the cost per cure from TT to multi-DAA therapy has been relatively constant. In order to cure more patients, either additional financial resources will need to be allocated to the treatment of HCV or drug costs will need to be reduced. Key words. HCV. DAA. SVR. Efficacy. INTRODUCTION SVR in HCV genotype 1 of approximately 90% while sig- nificantly improving tolerability and reducing adverse The landscape for treatment of HCV has changed dra- events.5 Subsequently, other multi-DAA regimens have matically. Prior to 2011, the standard of care was dual ther- been FDA approved, including ledipasvir (LDV)/ SOF, apy with pegylated interferon (peg-IFN) and ribavirin. ritonavir-boosted paritaprevir/ombitasvir with (3D-regi- That year the first direct-acting antivirals (DAAs), telapre- men) or without (2D-regimen) dasabuvir, and daclatasvir vir and boceprevir, were approved in combination with (DAC)/SOF.6-17 peg-IFN and ribavirin. This new triple-therapy (TT) regi- Multi-DAA regimens are revolutionizing HCV treat- men increased rates of SVR for HCV genotype 1 from 40% ment, expanding the number of patients eligible for treatment, to over 70%.1-4 The next big advance occurred in 2013 and reducing the resources needed to manage treatment- when both simeprevir (SMV) and sofosbuvir (SOF) were related side effects. A limitation to treatment is the cost of FDA-approved. Shortly thereafter, the interferon-free the DAAs (all values described in US dollars). Average combination of SMV/SOF was shown to achieve rates of wholesale price (AWP) of telaprevir and boceprevir in Manuscript received: August 26, 2016. Manuscript accepted: October 31, 2016. DOI:10.5604/16652681.1235479 Curing Chronic Hepatitis C. , 2017; 16 (3): 366-374 367 were estimated at $87,607 to $106,468 and $64,825 to tion or discontinuation, and post-treatment follow-up. All $95,845 for 24-week treatment regimens with peginterfer- healthcare utilization related to DAA treatment were cap- on and ribavirin, respectively.18-20 Combinations of SMV/ tured, including all relevant outpatient and inpatient visits SOF, LDV/SOF, 3D-regimen, 2D-regimen, and DAC/ and laboratory tests pre-, during, and post-treatment. Phar- SOF are estimated to cost $66,000 to $100,000 or more for macy utilization included prescribed medications use 12 weeks of treatment.21-24 based on DAA treatment protocols. Recorded utilization Although Phase III studies illustrated the efficacy of included all HCV-related outpatient clinic visits (OP), combination DAAs in various patient populations,6-17 and all available HCV-related inpatient (IP) and emergen- identifying real world efficacy and calculating treatment cy department (ED) encounters. All laboratory monitor- costs is essential for estimating resource utilization for ing was recorded by monitoring protocols (described in payer sources. In this study we examined the relationship detail below). Finally, the management of hematologic of treatment costs and treatment efficacy (SVR) to define side effects was measured by recording concomitant med- the cost per cure (cost per SVR) using real world observa- ications or therapies, including epoetin alfa, filgrastim, and tional data in patients who received a SMV/SOF multi- blood transfusions. DAA regimen compared to the prior standard of care, protease inhibitor-based TT. Monitoring protocols Study sample Study patients receiving drug therapy were divided into unique treatment protocols, defined by the Hepatology The study included all patients with HCV genotype 1 Clinic and reflecting national clinical guidelines. Each who underwent either multi-DAA or TT treatment at treatment protocol included monitoring of the following University of Colorado Health (UCH) Hepatology Clinic laboratory values: the complete blood count with manual between May 1, 2011 and December 31, 2014. Patients differential (CBC), comprehensive metabolic panel were identified using the electronic medical record (CMP), HCV RNA, HCV Genosure NS3/4A drug resist- (EMR) by conducting a manual chart review. The study ance assay (for genotype 1a patients prescribed SMV/SOF was approved by the Colorado Multiple Institutional Re- only), thyroid-stimulating hormone (TSH), liver function view Board (COMIRB). tests and pregnancy test for female patients of childbearing To be included in the analysis, patients had to be infect- potential prescribed ribavirin. These protocol-based labo- ed with HCV genotype 1a or 1b and treated with either ratory tests were drawn throughout treatment duration and simeprevir (150 mg daily) plus sofosbuvir (400 mg daily) varied in frequency depending on treatment regimen and for 12 to 24 weeks, telaprevir (750 mg TID) for 12 weeks length of therapy. plus peg-INF and ribavirin for 24 to 48 weeks, or bo- Figure 1 shows an overall comparison of SMV/SOF ceprevir (800 mg TID) plus peginterferon and ribavirin protocol to the TT protocol, highlighting the differ- for up to 48 weeks. Patients must have initiated treatment ence in frequency of monitoring tests across the two on or after May 1, 2011 and completed treatment by Sep- therapies. Following baseline, monitoring for SMV/ tember 30, 2014. Patients with HIV/HCV co-infection or SOF and TT protocols is marked on the vertical time- HBV/HCV co-infection, and recipients of organ trans- line through 12-48 week treatment regimens and fol- plantation were excluded. low-up viral load tests post-treatment. SMV/SOF patients received CBC and CMP less frequently than Data collection TT patients and were followed by post treatment HCV viral load tests four and twelve weeks after treatment, Demographic and clinical information while TT patients received an additional HCV RNA test twenty-four weeks post treatment. The monitoring pro- Demographic information, including gender, race, eth- tocol was adjusted for patients who discontinued treat- nicity and age at start of treatment were collected. Our clin- ment prematurely. ical variables included baseline body-mass index (BMI), genotype (1a or 1b), prior HCV treatment status, and level Outcomes of liver fibrosis: minimal (F0-F2) or advanced (F3-F4). The primary outcomes were: HCV related healthcare resource utilization • Rate of sustained virologic response. The number The defined HCV treatment duration of therapy was of patients in a given treatment regimen (SMV/SOF date of initiation of treatment through treatment comple- or TT) achieving SVR (through HCV RNA results) 368 Langness JA, et al. , 2017; 16 (3): 366-374 Week of treatment CBC w/ diff CMP HCV RNA HCV Genosure TSH PT/INR Pregnancy Test Baseline Wk0 XO XO XO X O XO XO Wk1 O - - - - - - Wk2XOX----- Wk3 O - - - - - - Wk4 XO - XO - - - - Wk5 O - - - - - - Wk6 O - - - - - - Wk7 O - - - - - - Wk8XO-O---- Wk10 O - - - - - - Wk12 XO XO XO - O XO - Wk14 O - - - - - - Wk16 O - - - - - - Wk18 O - - - - - - Wk20 O - - - - - - Wk24 O O O - O O - Wk28 O - - - - - - Wk32 O - - - - - - Wk36 O O O - O O - Wk40 O - - - - - - Wk44 O - - - - - - Wk48 O O O - O O - SVR4 XO XO XO - - XO - SVR12
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  • Technivie™ (Ombitasvir/Paritaprevir/Ritonavir) and Viekira XR™ (Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir) – Product Discontinuations

    Technivie™ (Ombitasvir/Paritaprevir/Ritonavir) and Viekira XR™ (Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir) – Product Discontinuations

    Technivie™ (ombitasvir/paritaprevir/ritonavir) and Viekira XR™ (dasabuvir/ombitasvir/paritaprevir/ritonavir) – Product discontinuations • On May 22, 2018, the FDA announced the discontinuation of AbbVie’s Technivie (ombitasvir/paritaprevir/ritonavir) and Viekira XR (dasabuvir/ombitasvir/paritaprevir/ritonavir). — Both product discontinuations are voluntary and due to changes in treatment practices in the current chronic HCV market in the U.S. and are not related to quality, safety or efficacy issues. • Viekira Pak™ (ombitasvir/paritaprevir/ritonavir with dasabuvir) will continue to be available due to reliance by countries outside the U.S. on FDA approval to support post-approval change to the label. However, Viekira Pak will not be promoted. • Viekira XR and Viekira Pak are indicated for the treatment of adult patients with chronic hepatitis C virus (HCV): — Genotype 1b infection without cirrhosis or with compensated cirrhosis — Genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin. — Viekira XR is a 4-drug fixed-dose combination, extended-release tablet containing dasabuvir 200 mg, ombitasvir 8.33 mg, paritaprevir 50 mg and ritonavir 33.33 mg that is dosed once daily. — Viekira Pak is a 3-drug fixed dose combination tablet containing ombitasvir 12.5 mg, paritaprevir 75 mg and ritonavir 50 mg copackaged with dasabuvir 250 mg tablets. The combination tablet is taken once daily and the dasabuvir tablet is taken twice daily. • Technivie is indicated in combination with ribavirin for the treatment of patients with genotype 4 chronic HCV infection without cirrhosis or with compensated cirrhosis. • Until January 1, 2019, supply of Technivie and Viekira XR will be available for all patients who begin therapy prior to July 1, 2018 to ensure that they are able to complete their course of prescribed therapy.