Zobair M Younossi1, Maria Stepanova2, Quentin M Anstee3, Eric J Lawitz4, Vincent Wai-Sun Wong5, Manuel Romero-Gomez6, Kathryn Kersey7, Georgia Li7, G Mani Subramanian7, Robert P Myers7, C Stephen Djedjos7, Takeshi Okanoue8, Michael Trauner9, Zachary Goodman10, Stephen A Harrison11. 1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org. 2. Center for Outcomes Research in Liver Disease (COR-LD), Washington, District of Columbia. 3. Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle-upon-Tyne, and Newcastle NIHR Biomedical Research Centre, Newcastle-upon-Tyne, United Kingdom. 4. Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Texas. 5. Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong. 6. Hospital Universitario Virgen del Rocio, Sevilla, Spain. 7. Gilead Sciences, Inc, Foster City, California. 8. Saiseikai Suita Hospital, Suita City, Osaka, Japan. 9. Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 10. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia. 11. Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
Abstract
BACKGROUND: Patient-reported outcomes (PROs) are used to measure patients' experience with their disease. However, there are few PRO data from patients with NASH. We collected data from the STELLAR clinical trials to assess PROs for NASH and advanced fibrosis. METHODS: We analyzed data from 1667 patients (58 ± 9 years, 40% male, 52% with cirrhosis, 74% with diabetes) with NASH and bridging fibrosis or compensated cirrhosis (metavir scores, F3 or F4) enrolled in the phase 3 STELLAR trials of selonsertib (NCT03053050 and NCT03053063) who completed PRO questionnaires (SF-36, CLDQ-NASH, EQ-5D, or WPAI:SHP) before treatment initiation. RESULTS: Compared with patients with F3 fibrosis, higher proportions of patients with F4 fibrosis were female, were white, had more hematologic and gastrointestinal comorbidities, and had type 2 diabetes (P ≤ .01). Mean physical health-related PRO scores were significantly lower than those of the general population: patients with F4 fibrosis had score reductions of 4.4% to 12.9% in 6/8 SF-36 domains and patients with F3 fibrosis had score reductions of 3.9% to 11.7% in 4/8 domains (P < .01). Compared to patients with F3 fibrosis, those with F4 fibrosis had lower scores in all but 1 domains of CLDQ-NASH, Role Physical, Bodily Pain, and Social Functioning domains of the SF-36, and EQ-5D (P ≤ 01). In multivariate regression analysis, factors independently associated with lower PRO scores included having cirrhosis, female sex, higher body mass index, history of smoking, and diabetes or other comorbidities (P < .01). CONCLUSIONS: PROs are significantly lower in patients with NASH with advanced fibrosis who participated in the STELLAR clinical trials. Treatment of patients with NASH should focus on improving not only clinical outcomes but also quantifiable symptom burden and health-related quality of life.
BACKGROUND:Patient-reported outcomes (PROs) are used to measure patients' experience with their disease. However, there are few PRO data from patients with NASH. We collected data from the STELLAR clinical trials to assess PROs for NASH and advanced fibrosis. METHODS: We analyzed data from 1667 patients (58 ± 9 years, 40% male, 52% with cirrhosis, 74% with diabetes) with NASH and bridging fibrosis or compensated cirrhosis (metavir scores, F3 or F4) enrolled in the phase 3 STELLAR trials of selonsertib (NCT03053050 and NCT03053063) who completed PRO questionnaires (SF-36, CLDQ-NASH, EQ-5D, or WPAI:SHP) before treatment initiation. RESULTS: Compared with patients with F3 fibrosis, higher proportions of patients with F4 fibrosis were female, were white, had more hematologic and gastrointestinal comorbidities, and had type 2 diabetes (P ≤ .01). Mean physical health-related PRO scores were significantly lower than those of the general population: patients with F4 fibrosis had score reductions of 4.4% to 12.9% in 6/8 SF-36 domains and patients with F3 fibrosis had score reductions of 3.9% to 11.7% in 4/8 domains (P < .01). Compared to patients with F3 fibrosis, those with F4 fibrosis had lower scores in all but 1 domains of CLDQ-NASH, Role Physical, Bodily Pain, and Social Functioning domains of the SF-36, and EQ-5D (P ≤ 01). In multivariate regression analysis, factors independently associated with lower PRO scores included having cirrhosis, female sex, higher body mass index, history of smoking, and diabetes or other comorbidities (P < .01). CONCLUSIONS: PROs are significantly lower in patients with NASH with advanced fibrosis who participated in the STELLAR clinical trials. Treatment of patients with NASH should focus on improving not only clinical outcomes but also quantifiable symptom burden and health-related quality of life.
Authors: Hani Shamseddeen; Eduardo Vilar-Gomez; Naga Chalasani; Robert P Myers; G Mani Subramanian; Harold H Shlevin; Adam E Allgood; Eric S Orman Journal: Drug Saf Date: 2020-03 Impact factor: 5.606
Authors: Zobair M Younossi; Maria Stepanova; Mazen Noureddin; Kris V Kowdley; Simone I Strasser; Anita Kohli; Peter Ruane; Mitchell L Shiffman; Aasim Sheikh; Nadege Gunn; Stephen H Caldwell; Ryan S Huss; Robert P Myers; Vincent Wai-Sun Wong; Naim Alkhouri; Zachary Goodman; Rohit Loomba Journal: Hepatol Commun Date: 2021-05-12
Authors: William R Treem; Melissa Palmer; Isabelle Lonjon-Domanec; Daniel Seekins; Lara Dimick-Santos; Mark I Avigan; John F Marcinak; Ajit Dash; Arie Regev; Eric Maller; Meenal Patwardhan; James H Lewis; Don C Rockey; Adrian M Di Bisceglie; James W Freston; Raul J Andrade; Naga Chalasani Journal: Drug Saf Date: 2020-11-03 Impact factor: 5.606