Zobair M Younossi1, Maria Stepanova2, Eric Lawitz3, Michael Charlton4, Rohit Loomba5, Robert P Myers6, Mani Subramanian6, John G McHutchison6, Zachary Goodman7. 1. Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA. 2. Center for Outcomes Research in Liver Diseases, Washington, DC, USA. 3. Texas Liver Institute, San Antonio, TX, USA. 4. Intermountain Medical Center, Salt Lake City, UT, USA. 5. University of California San Diego, La Jolla, CA, USA. 6. Gilead Sciences, Inc., Foster City, CA, USA. 7. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
Abstract
BACKGROUND: Patient-reported outcomes (PROs) represent patients' perspective about their well-being. AIM: To assess PRO changes in patients with non-alcoholic steatohepatitis (NASH) after treatment withselonsertib (SEL) and to associate them with different biomarkers. METHODS:Patients with NASH and stage 2-3 fibrosis receivedSEL 6 mg or 18 mg orally QD alone or in combination with simtuzumab (SIM, 125 mg SC weekly) or SIM alone for 24 weeks. Biopsies were obtained at baseline and at treatment week 24. PROs were assessed using SF-36, CLDQ and WPAI:SHP. RESULTS:Seventy-two patients with NASH were included (54 ± 10 years, 31% male, 65% stage 3, 71% diabetes). Baseline physical health-related PRO scores were significantly lower than population norms (P < .05). During treatment, there were no consistent differences in treatment-emergent PRO changes between different regimens (P > .05). However, NASH subjects who experienced ≥2 decrease in NAFLD Activity Score or ≥1-stage reduction in fibrosis showed significant improvements in their PROs (up to +15.5% of a PRO range size, P < .05). Additionally, improvements in PROs (up to +21.5%, P < .05) were noted in patients with at least 50% relative reduction in collagen, while NASH subjects with >17% increase in their collagen experienced PRO worsening (up to -13.9%, P < .05). Baseline serum CK-18, IL-6 and CRP significantly correlated with PROs (rho from -0.24 to -0.38, P < .05). CONCLUSIONS: A decrease in hepatic collagen is the most prominently associated with improvement of PROs in NASH patients with F2-F3 treated with SEL. Furthermore, serum cytokines are associated with baseline PROs and with treatment-emergent changes in PROs in patients with NASH.
RCT Entities:
BACKGROUND:Patient-reported outcomes (PROs) represent patients' perspective about their well-being. AIM: To assess PRO changes in patients with non-alcoholic steatohepatitis (NASH) after treatment with selonsertib (SEL) and to associate them with different biomarkers. METHODS:Patients with NASH and stage 2-3 fibrosis received SEL 6 mg or 18 mg orally QD alone or in combination with simtuzumab (SIM, 125 mg SC weekly) or SIM alone for 24 weeks. Biopsies were obtained at baseline and at treatment week 24. PROs were assessed using SF-36, CLDQ and WPAI:SHP. RESULTS: Seventy-two patients with NASH were included (54 ± 10 years, 31% male, 65% stage 3, 71% diabetes). Baseline physical health-related PRO scores were significantly lower than population norms (P < .05). During treatment, there were no consistent differences in treatment-emergent PRO changes between different regimens (P > .05). However, NASH subjects who experienced ≥2 decrease in NAFLD Activity Score or ≥1-stage reduction in fibrosis showed significant improvements in their PROs (up to +15.5% of a PRO range size, P < .05). Additionally, improvements in PROs (up to +21.5%, P < .05) were noted in patients with at least 50% relative reduction in collagen, while NASH subjects with >17% increase in their collagen experienced PRO worsening (up to -13.9%, P < .05). Baseline serum CK-18, IL-6 and CRP significantly correlated with PROs (rho from -0.24 to -0.38, P < .05). CONCLUSIONS: A decrease in hepatic collagen is the most prominently associated with improvement of PROs in NASH patients with F2-F3 treated with SEL. Furthermore, serum cytokines are associated with baseline PROs and with treatment-emergent changes in PROs in patients with NASH.
Authors: Daniel J de Klerk; Mark J de Keijzer; Lionel M Dias; Jordi Heemskerk; Lianne R de Haan; Tony G Kleijn; Leonardo P Franchi; Michal Heger Journal: Methods Mol Biol Date: 2022
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