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Long‐term follow‐up of clinical trial patients treated for chronic HCV infection with daclatasvir‐based regimens
Author(s) -
Reddy K. Rajender,
Pol Stanislas,
Thuluvath Paul J.,
Kumada Hiromitsu,
Toyota Joji,
Chayama Kazuaki,
Levin James,
Lawitz Eric J.,
Gadano Adrian,
Ghesquiere Wayne,
Gerken Guido,
Brunetto Maurizia R.,
Peng ChengYuan,
Silva Marcelo,
Strasser Simone I.,
Heo Jeong,
McPhee Fiona,
Liu Zhaohui,
Yang Rong,
Linaberry Misti,
Noviello Stephanie
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13596
Subject(s) - daclatasvir , medicine , hepatocellular carcinoma , gastroenterology , ns5a , cirrhosis , hepatitis c virus , hepatitis c , virology , ribavirin , hepacivirus , virus
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.