Long‐term follow‐up of clinical trial patients treated for chronic HCV infection with daclatasvir‐based regimens |
| |
| Authors: | K. Rajender Reddy Stanislas Pol Paul J. Thuluvath Hiromitsu Kumada Joji Toyota Kazuaki Chayama James Levin Eric J. Lawitz Adrian Gadano Wayne Ghesquiere Guido Gerken Maurizia R. Brunetto Cheng‐Yuan Peng Marcelo Silva Simone I. Strasser Jeong Heo Fiona McPhee Zhaohui Liu Rong Yang Misti Linaberry Stephanie Noviello |
| |
| Affiliation: | 1. School of Medicine, University of Pennsylvania, Philadelphia, PN, USA;2. H?pital Cochin, Paris, France;3. Mercy Medical Center, Baltimore, MD, USA;4. Toranomon Hospital, Tokyo, Japan;5. Sapporo‐Kosei General Hospital, Sapporo, Japan;6. Hiroshima University, Hiroshima, Japan;7. Dean Foundation, Madison, WI, USA;8. Texas Liver Institute, University of Texas Health Sciences Center, San Antonio, TX, USA;9. Hospital Italiano de Buenos Aires, Buenos Aires, Argentina;10. Vancouver Island Health Authority, University of British Columbia, Victoria, BC, Canada;11. University of Duisburg‐Essen, Essen, Germany;12. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;13. School of Medicine, China Medical University, Taichung, Taiwan;14. Hospital Universitario Austral, Buenos Aires, Argentina;15. Royal Prince Alfred Hospital, Sydney, NSW, Australia;16. College of Medicine, Medical Research Institute, Pusan National University Hospital, Pusan National University, Busan, Korea;17. Bristol‐Myers Squibb, Wallingford, CT, USA;18. Bristol‐Myers Squibb, Hopewell, NJ, USA;19. Bristol‐Myers Squibb, Princeton, NJ, USA |
| |
| Abstract: | Background & Aims Daclatasvir has achieved high sustained virologic response (SVR) rates in diverse hepatitis C virus (HCV) populations. This study evaluated the long‐term efficacy and safety of daclatasvir‐based regimens administered during clinical studies. Methods Patients enrolled within 6 months of parent study completion or protocol availability at the study sites. The primary objective was durability of SVR at follow‐up Week 12 (SVR12). Secondary objectives included analysing HCV sequences in non‐responders or responders who relapsed, and characterization of liver disease progression. Results Between 24 February 2012 and 17 July 2015, this study enrolled and began following 1503 recipients of daclatasvir‐based regimens (follow‐up cut‐off, 13 October 2015); 60% were male, 18% aged ≥65 years, 87% had genotype‐1a (42%) or ‐1b (45%) infection, and 18% had cirrhosis. Median follow‐up from parent study follow‐up Week 12 was 111 (range, 11‐246) weeks. 1329/1489 evaluable patients were SVR12 responders; 1316/1329 maintained SVR until their latest visit. Twelve responders relapsed by (n = 9) or after (n = 3) parent study follow‐up Week 24; one was reinfected. Relapse occurred in 3/842 (0.4%) and 9/487 (2%) responders treated with interferon‐free or interferon‐containing regimens, respectively. Hepatic disease progression and new hepatocellular carcinoma were diagnosed in 15 and 23 patients, respectively. Among non‐responders, emergent non‐structural protein‐5A (NS5A) and ‐3 (NS3) substitutions were replaced by wild‐type sequences in 27/157 (17%) and 35/47 (74%) patients, respectively. Conclusions SVR12 was durable in 99% of recipients of daclatasvir‐based regimens. Hepatic disease progression and new hepatocellular carcinoma were infrequent. Emergent NS5A substitutions persisted longer than NS3 substitutions among non‐responders. |
| |
| Keywords: | chronic hepatitis C virus daclatasvir hepatocellular carcinoma long‐term follow‐up sustained virologic response |
|
|
