Original research Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2019-002060 on 7 February 2020. Downloaded from Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients Luis Margusino- Framiñán,1,2 Purificación Cid- Silva,1,2 Sandra Rotea- Salvo,1 Álvaro Mena- de- Cea,2,3 Francisco Suárez- López,4 Pilar Vázquez- Rodríguez,2,3 Manuel Delgado- Blanco,2,4 Ana Isabel Sanclaudio- Luhia,5 Isabel Martín- Herranz,1 Ángeles Castro- Iglesias2,3 1Pharmacy Service, Universitary ABSTRact 1.1%, with a total affected population of 5.6 million Hospital of A Coruña, A Objectives Sofosbuvir/velpatasvir±ribavirin (SOF/ people.1 The prevalence of HCV genotypes varies Coruña, Spain 2 among regions, with genotype 3 (G3) being the Division of Clinical Virology, VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are Biomedical Research Institute the drug combinations of choice for treating individuals second most prevalent in Europe after genotype 1 of A Coruña (INIBIC), with genotype 3 hepatitis C virus (G3- HCV) infection. The (G1), accounting for approximately 25% of cases Universitary Hospital of A objective of this study was to evaluate the effectiveness of chronic hepatitis C (CHC).2 Compared with Coruña (CHUAC), Sergas, and safety of SOF/VEL±RBV compared with GLE/PIB for G1- HCV, G3- HCV chronic infection has a faster University of A Coruña (UDC), 3–6 A Coruña, Spain treating G3- HCV infection under routine clinical practice progression to liver cirrhosis and hepatocellular 7 3Infectious Diseases Unit. conditions. carcinoma (HCC), and is associated with a higher Internal Medicine Service, Methods We conducted a prospective observational incidence of hepatic steatosis.8–11 Furthermore, Universitary Hospital of A cohort study of individuals with G3- HCV infection compared with other genotypes, G3- HCV has been Coruña (CHUAC), A Coruña, reported to exhibit lower rates of sustained virologic Spain who initiated treatment with SOF/VEL +/-RBV or GLE/ 4Hepatology Unit, Digestive PIB between April 2017 and July 2018. Prisoners response (SVR) with direct-acting antivirals (DAAs), System Service, University and children were excluded. The outcome variable of particularly in patients with advanced liver fibrosis Hospital of A Coruña (CHUAC), effectiveness was sustained virological response 12 and non- responders to previous treatment.12 There- A Coruña, Spain weeks after completing treatment (SVR12). The safety fore, the evaluation of the effectiveness of antiviral 5Information Systems Department, University variable was withdrawal secondary to severe adverse treatment against G3-HCV chronic infection under Hospital of A Coruña, A events (SAEs). Covariates included sex, age, HIV co- clinical practice conditions in the era of DAAs is of Coruña, Spain infection, previous liver transplant, cirrhosis, hepatic special interest. fibrosis and previous antiviral treatment. Statistical The treatment of G3- HCV recommended by scien- Correspondence to significance was calculated using Fisher’s exact test or tific societies has changed in recent years. Taking the Dr Luis Margusino- Framiñán, the Mann–Whitney U- test. results of clinical studies into account, the European Pharmacy, XXI A Coruña, A Coruña 15006, Spain; Luis. Results A total of 76 patients were included in Association for the Study of the Liver (EASL) has Margusino. Framinan@ sergas. the analysis, of whom 46 were treated with SOF/ repeatedly updated its recommendations, which have es VEL±RBV and 30 were treated with GLE/PIB. No baseline advised the use of peginterferon (PegIFN)+ribavirin http://ejhp.bmj.com/ differences were observed between treatment groups (RBV) (2011), sofosbubir (SOF)+PegIFN+ RBV, Received 6 August 2019 SOF+RBV (2013, 2015), SOF+daclatasvir Revised 14 January 2020 with respect to age, sex, HIV co- infection, fibrosis stage, Accepted 16 January 2020 cirrhosis and previous antiviral treatment. Of the patients (DAC)±RBV, SOF/velpatasvir (VEL)±RBV (2016), Published Online First treated with SOF/VEL±RBV and GLE/PIB, 95.7% and SOF/VEL, glecaprevir/pibrentasvir (GLE/PIB) and 7 February 2020 96.7% reached SVR12, respectively (P=0.7). Of patients SOF/VEL/voxilaprevir (VOX) (2018).13–17 The Infec- EAHP Statement 6: Education with and without cirrhosis, 83.3% and 98.4% reached tious Diseases Society of America (IDSA) and Amer- and Research. SVR12, respectively (P=0.09). Of the patients with ican Association for the Study of the Liver (AASLD) on October 2, 2021 by guest. Protected copyright. low- grade hepatic fibrosis (F0-2) and advanced fibrosis have also updated their treatment recommenda- (F3-4), 100% and 85.7% reached SVR12, respectively tions, with the most recent update being in 2018.18 (P=0.03). In treatment- naïve and treatment- experienced Table 1 provides a summary of the current treatment patients, 95.7% and 100% reached SVR12, respectively recommendations by EASL and IDSA/AASLD.17 18 (P=0.57), without significant differences independent of However, there have been no studies published that the treatment group (P=0.28 for SOF/VEL±RBV; P=0.18 compare the safety and effectiveness of these thera- for GLE/PIB). The incidence of AEs was 21.1% (95% CI pies in individuals with G3-HCV infection. 11.3% to 30.9%). None of the patients developed an The objective of this study was to evaluate the SAE or required antiviral treatment withdrawal. effectiveness and safety of 8- to 24-week treat- © European Association of Conclusions SOF/VEL±RBV or GLE/PIB are safe and ment regimens of SOF/VEL±RBV and GLE/PIB for Hospital Pharmacists 2020. No commercial re- use. See rights effective for treating G3- HCV- infections, with a lower treating G3- HCV infection under routine clinical and permissions. Published effectiveness in patients with advanced fibrosis F3-4. practice conditions. by BMJ. METHODS To cite: Margusino- Framiñán L, Cid- Silva P, Study design and patient selection Rotea- Salvo S, et al. INTRODUCTION We conducted an observational, prospective, cohort Eur J Hosp Pharm It is estimated that the prevalence of chronic hepatitis study of patients with G3-HCV infection who started 2020;27:e41–e47. C virus (HCV) infection in Europe is approximately HCV treatment with SOF/VEL±RBV or GLE/PIB Margusino- Framiñán L, et al. Eur J Hosp Pharm 2020;27:e41–e47. doi:10.1136/ejhpharm-2019-002060 e41 Original research Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2019-002060 on 7 February 2020. Downloaded from liver fibrosis (Fibroscan, Echosens, Paris, France), and patients Table 1 Adaptation of the treatment recommendations of EASL and were stratified according to stiffness results into fibrosis F0-1 IDSA/AASLD of patients infected with genotype 3 of the hepatitis C (<7.6 kPa), F2 (7.6–9.5 kPa), F3 (9.6–14.4 kPa) or F4 (>14.4 kPa virus, without cirrhosis or with compensated cirrhosis. recommended in HCV mono- infected patients and >14.0 kPa in HIV co-in - treatments.Update 2018 *†17 18 fected patients).20 21 17 18 Genotype 3- infected patient EASL IDSA/AASLD Adherence rates were calculated following continuous Naïve- non cirrhotic SOF/VEL 12 w SOF/VEL 12 w measurement of the medication acquisition (CMA) method,22 GLE/PIB 8 w GLE/PIB 8 w during the monthly visits to the Hospital Pharmacy Service Treatment experienced- non SOF/VEL 12 w SOF/VEL±RBV 12 w where the study was conducted. This method measured cumu- cirrhotic‡ GLE/PIB 12 w lative days' supply obtained over a series of intervals/total days Naïve- cirrhotic GLE/PIB 12 w SOF/VEL 12 w from the beginning to the end of the time period. Drug-drug SOF/VEL/VOX 12 w GLE/PIB 12 w interactions (DDIs) were identified by the clinical team (clin- Treatment experienced- cirrhotic‡ SOF/VEL/VOX 12 w ELB/GRZ+SOF 12 w ical pharmacists, hepatologists and infectious disease special- GLE/PIB 16 w SOF/VEL/VOX 12 w ists) using the Hep Drug Interactions database of the University *This table is a simplified adaptation. It is recommended to consult the direct of Liverpool,23 recommended as reference by EASL.17 If there references. was no information available in this database, Lexicomp Drug †Ribavirin addition is recommended in some subgroups of patients. 24 25 ‡Recommendations in experienced patients are different and vary depending on Interactions, IBM Micromedex, analysis of pharmacokinetic whether the previous treatment was based on peginterferon or DAAs. parameters available in the technical data sheet and consultation AASLD, American Association for the Study of the Liver; EASL, European Association with the DAA manufacturing laboratory were employed. for the Study of the Liver; ELB, elbasvir; GLE, glecaprevir; GRZ, grazoprevir; IDSA, The primary effectiveness endpoint was the proportion of Infectious Diseases Society of America; PIB, pibrentasvir; RBV, ribavirina; SOF, patients with SVR12, defined as an undetectable HCV ribonu- sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir. cleic acid (HCV- RNA) 12 weeks' post- treatment. Secondary effi- cacy variables included treatment failure (detectable HCV-RNA between April 2017 and July 2018 and had reached week 12 in a patient with previous undetectable HCV-RNA on treatment), post- treatment by January 2019. Infectious disease specialists relapse (detectable HCV-RNA 12 weeks' post- treatment in a and hepatologists chose the antiviral treatment regimen, taking patient with undetectable HCV-RNA at the end of treatment), into account not only the prevailing clinical practice conditions virological failure (HCV- RNA level remaining above the LOD 17 18 and international recommendations, but also variables such throughout treatment) or missing HCV- RNA data 12 weeks' as concomitant treatment, lifestyle habits or patient preferences. post- treatment due to on- treatment withdrawal secondary to The therapeutic regimen was a daily fixed combination of SOF severe AEs (SAEs) or death. 400 mg/VEL 100 mg (Epclusa; Gilead Sciences International The primary safety endpoint was the percentage of treatment Ltd) with or without the addition of RBV (Ribavirina Normon; withdrawal secondary to SAEs.