Improvement of hepatic fibrosis and patient‐reported outcomes in non‐alcoholic steatohepatitis treated with selonsertib

Abstract Background Patient‐reported outcomes ( PRO s) 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. PRO s 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 PRO s (up to +15.5% of a PRO range size, P < .05). Additionally, improvements in PRO s (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 PRO s (rho from −0.24 to −0.38, P < .05). Conclusions A decrease in hepatic collagen is the most prominently associated with improvement of PRO s in NASH patients with F2‐F3 treated with SEL . Furthermore, serum cytokines are associated with baseline PRO s and with treatment‐emergent changes in PRO s in patients with NASH .