Abstract
Introduction
Some direct-acting antiviral regimens for hepatitis C virus (HCV) infection pose safety or efficacy concerns if coadministered with drugs containing ethinyl estradiol. The present analysis was conducted to examine the impact of concomitant oral contraceptive pills (OCP) or hormone replacement therapy (HRT) during treatment with elbasvir (EBR)/grazoprevir (GZR) in women with HCV genotype (GT)1 or GT4 infection.
Methods
This is a post hoc, integrated retrospective analysis of female participants with HCV GT1 or GT4 infection who received EBR 50 mg/GZR 100 mg once daily for 12 weeks in phase 2/3 clinical trials. The primary end point was sustained virologic response at 12 weeks after therapy completion (SVR12). For this analysis, participants were stratified according to whether they received OCP or HRT during the original treatment study.
Results
A total of 1,022 women with HCV GT1 or GT4 infection were included (receiving OCP/HRT, n=81; not receiving OCP/HRT, n=941). Most participants receiving OCP/HRT were treatment-naive (79%), noncirrhotic (91.4%), and aged >35 years (71.6%). SVR12 rates were similar in women receiving OCP/HRT and those not receiving OCP/HRT (95.1% vs 96.3%). SVR12 rates remained high across all subgroups within the population receiving OCP/HRT: SVR12 rates were 94.6%, 100%, and 100% in participants with GT1a, GT1b, and GT4 infection, and all women aged 18–35 years achieved SVR (21/21). Treatment-related adverse events occurred in 40.7% (33/81) and 30.1% (283/941) of women receiving and those not receiving OCP/HRT, respectively.
Conclusion
The efficacy and safety of EBR/GZR administered for 12 weeks was similar in women receiving OCP/HRT and those not on OCP/HRT. These data indicate that EBR/GZR can be safely used for the treatment of HCV GT1 or GT4 infection in women receiving concomitant OCP/HRT.
Supplementary materials
Table S1 OCP and HRT therapies coadministered with EBR/GZR in contributing phase 2/3 studies
Table S2 Reasons for using OCP/HRT medications
Table S3 Serious adverse events
Acknowledgment
We extend our gratitude to the participants, their families, investigators, and site personnel who participated in this study. Medical writing and editorial assistance was provided by Tim Ibbotson, PhD, of ApotheCom, Yardley, PA, and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The trials included in this integrated analysis were sponsored and funded in full by MSD. MSD contributed to the trial design, study execution and management, data collection, and statistical analyses of the original treatment studies, and also conducted the integrated analysis described in this report. Portions of the data described in the manuscript were previously presented at The International Liver Congress; April 11–15, 2018; Paris, France [abstract #801].
Data sharing statement
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA’s data sharing policy, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the EngageZone site or via email to [email protected].
Disclosure
Dr Hézode has received personal fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, and MSD. Dr Kwo received grants from the Regenstrief Institute and Target Registeries, has received grants and personal fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, MSD, and Janssen, and has received personal fees from Quest, Arrowhead, Surrozen, Ferring, Conatus, Dova and Shinogi. Dr Sperl has received grants from Gilead Sciences and personal fees from Gilead Sciences, MSD, AbbVie, Herbacos Recordati, and Intercept. Drs Hwang, Robertson, and Haber are current employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and stockholders in Merck & Co., Inc., Kenilworth, NJ, USA. Drs Long and Talwani were employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, at the time that the study was conducted. The authors report no other conflicts of interest in this work.