Patient-reported outcomes (PROs) are important endpoints for clinical trials. The impact of
investigational drugs on PROs of patients with advanced
nonalcoholic steatohepatitis (NASH) was investigated. Patients with NASH with bridging
fibrosis or compensated
cirrhosis were enrolled in a phase 2, randomized, placebo-controlled study of
selonsertib,
firsocostat, or
cilofexor, alone or in two-
drug combinations (NCT03449446). PROs included Short Form 36 (SF-36), Chronic
Liver Disease Questionnaire (CLDQ)-NASH, EuroQol Five Dimension (EQ-5D), Work Productivity and Impairment (WPAI), and 5-D Itch before and during treatment. A total of 392 patients with NASH (mean ± SD, 60 ± 9 years old; 35% men; 89% white; 72% diabetes; and 56% compensated
cirrhosis) were included. Baseline Physical Functioning (PF) and Bodily
Pain of SF-36 and
Fatigue and Worry of CLDQ-NASH were significantly lower in patients with
cirrhosis (total CLDQ-NASH score mean ± SD, 4.91 ± 1.06 with
cirrhosis vs. 5.16 ± 1.14 without
cirrhosis; P < 0.05). Lower baseline PRO scores were independently associated with age, female sex, greater body mass index, diabetes, clinically overt
fatigue, and comorbidities (all P < 0.05). After 48 weeks of treatment, patients with ≥1-stage
fibrosis improvement without worsening of NASH experienced improvement in EQ-5D and five out of six CLDQ-NASH domains (P < 0.05). Patients with ≥2-point decrease in their
nonalcoholic fatty liver disease activity score (
NAS) also had improvements in PF and Role Physical scores and all domains of CLDQ-NASH (P < 0.05). Progression to
cirrhosis was associated with a decrease in PF scores of SF-36 (P ≤ 0.05).
Fibrosis regression was independently associated with greater improvements in PF and EQ-5D scores, while
NAS improvement was associated with improvement in
fatigue and
pruritus (all P < 0.05). Conclusion: Patients with advanced NASH experienced improvement in their PROs after
fibrosis regression or improvement in disease activity.