Whalley D, Twiss J, Doward L, Balp MM, Brass C, Tietz A, Loeffler J, Lopez P, Lawitz EJ, Sanyal AJ. A novel patient-reported outcome measure indicates low burden of treatment among patients with non-alcoholic steatohepatitis: interim results from a phase 2 trial of tropifexor. Poster presented at the AASLD 2020 annual meeting; November 13, 2020. Boston, MA. [abstract] Hepatology. 2020 Oct 1; 72(S1):1005A. doi: 10.1002/hep.31579

BACKGROUND: Interim results from a randomized, double-blind, placebo-controlled trial of tropifexor (TXR; a non-bile acid farnesoid X receptor agonist) (FLIGHT-FXR; NCT02855164) demonstrated improvements in several relevant clinical biomarkers compared with placebo at week 12 in patients with nonalcoholic steatohepatitis (NASH). This analysis describes for the first time week 12 results from a novel patient-reported outcome measure, NASH-CHECK, which assesses NASH-specific symptoms and health-related quality of life (HRQOL).

METHODS: 152 patients with stage 2 or 3 fibrotic (F2, F3) NASH were randomized to TXR 200 mcg (n = 51), TXR 140 mcg (n = 50), or placebo (n = 51). Descriptive analyses of NASH-CHECK scores were conducted using interim data up to week 12. NASH-CHECK has 28 items assessing symptoms (9 items) and HRQOL (19 items). Scores range from 0 to 10; higher scores indicate worse symptoms/HRQOL.

RESULTS: NASH-CHECK data were available for 149 patients (65% female; mean [standard deviation (SD)] age, 55 [11] years; 42% F2, 58% F3; mean [SD] body mass index, 35 [6]; 59% type 2 diabetes). Table 1 shows that mean NASH-CHECK scores were low at baseline, indicating low levels of symptoms and HRQOL impacts in the sample. Percentages of patients reporting issues at baseline (NASH-CHECK scale score > 0) were: Abdominal Pain, 40%; Abdominal Bloating, 57%, Fatigue, 76%; Sleep, 67%; Itchy Skin, 55%; Cognitive Symptoms, 73%; Activity Limitations, 74%; Emotional Impact, 89%; and Social Impact, 49%. Table 1 further shows that NASH-CHECK scores were generally stable over the study period, with overall mean scale scores remaining low at weeks 6 and 12 across all treatment groups. Although Itchy Skin scores increased in both TXR groups (Table 1), the mean [SD] scores for the subsamples of patients reporting itch at each time point (patients with scale score > 0) were low (baseline: TXR 200 mcg 2.59 [1.87], TXR 140 mcg 3.14 [2.12], placebo 2.81 [2.06]; week 12: TXR 200 mcg 3.68 [2.89], TXR 140 mcg 3.68 [2.77], placebo 2.71 [1.92]).

CONCLUSION: After 12 weeks of TXR treatment, patient-reported symptoms and HRQOL remained stable overall, indicating the likely acceptability of long-term treatment with TXR. Itch was reported in some patients treated with TXR over the study period, but mean scores for those reporting itch remained low. The end-of-study, 48-week data will further inform conclusions about the stability of symptoms and HRQOL in patients treated with TXR.

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