TY - JOUR
T1 - Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis
T2 - REGENERATE 18-Month Interim Analysis
AU - RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) Study Investigators
AU - Younossi, Zobair M.
AU - Stepanova, Maria
AU - Nader, Fatema
AU - Loomba, Rohit
AU - Anstee, Quentin M.
AU - Ratziu, Vlad
AU - Harrison, Stephen
AU - Sanyal, Arun J.
AU - Schattenberg, Jörn M.
AU - Barritt, A. Sidney
AU - Noureddin, Mazen
AU - Bonacci, Martin
AU - Cawkwell, Gail
AU - Wong, Bruce
AU - Rinella, Mary
N1 - Funding Information:
The authors thank medical writer Raghav Pandey, PhD, ProEd Communications, Inc, for editorial assistance with this manuscript. Further editorial assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and was funded by Intercept Pharmaceuticals, Inc. Zobair M. Younossi, (Conceptualization: Equal; Formal analysis: Lead; Methodology: Lead; Supervision: Lead; Validation: Lead; Writing – review & editing: Equal), Maria Stepanova (Data curation: Lead; Formal analysis: Equal; Validation: Equal; Writing – review & editing: Equal), Fatema Nader (Project administration: Lead; Supervision: Supporting; Writing – review & editing: Equal), Rohit Loomba (Conceptualization: Equal; Methodology: Supporting; Writing – review & editing: Equal), Quentin M. Anstee (Conceptualization: Equal; Methodology: Supporting; Writing – review & editing: Equal), Vlad Ratziu (Conceptualization: Equal; Methodology: Equal; Writing – review & editing: Equal), Stephen Harrison (Conceptualization: Equal; Methodology: Supporting; Writing – review & editing: Equal), Arun J. Sanyal (Conceptualization: Equal; Methodology: Supporting; Validation: Equal; Writing – review & editing: Equal), Jörn M. Schattenberg (Conceptualization: Equal; Methodology: Supporting; Writing – review & editing: Equal), A. Sidney Barritt (Writing – review & editing: Equal), Mazen Noureddin (Writing – review & editing: Equal), Martin Bonacci (Methodology: Equal; Writing – original draft: Equal; Writing – review & editing: Equal), Gail Cawkwell (Conceptualization: Supporting; Resources: Equal; Supervision: Equal; Writing – review & editing: Equal), Bruce Wong (Project administration: Lead; Writing – original draft: Equal; Writing – review & editing: Equal), Mary Rinella (Conceptualization: Equal; Methodology: Supporting; Writing – review & editing: Supporting) Conflicts of interest The authors disclose the following: Zobair M. Younossi has received research funds and/or consultation fees from Gilead Sciences, NovoNordisk, Intercept, Novartis, Terns, Viking, Siemens, and Echosens; Maria Stepanova received a grant from Intercept; Fatema Nader received a grant from Intercept; Rohit Loomba serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse Bio, GNI, GRI Bio, Intercept, Ionis, Janssen, Inc, Merck, Metacrine, Inc, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics, his institution has received grant support from Allergan, Boehringer Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens, and he is a co-founder of Liponexus, Inc; Quentin M. Anstee has consulted on behalf of Newcastle University from Acuitas Medical, Allergan/Tobira, E3Bio, Eli Lilly & Company, Ltd, Galmed, Genfit SA, Gilead, Grunthal, Imperial Innovations, Intercept Pharma Europe, Ltd, Inventiva, Janssen, MedImmune, NewGene, Pfizer, Ltd, Raptor Pharma, Novartis Pharma AG, BMS, NGMBio, Madrigal, Servier, EcoR1, 89Bio, Altimmune, AstraZeneca, Axcella, Blade, BNN Cardio, Celgene, Cirius, CymaBay, Genentech, HistoIndex, Indalo, IQVIA, Metacrine, North Sea Therapeutics, Novo Nordisk, Poxel, Terns, and Viking Therapeutics, has received grants from Allergan/Tobira, Genfit SA, Intercept Pharma Europe Ltd, Pfizer, Ltd, Novartis Pharma AG, AbbVie, GSK, AstraZeneca, and Glympse Bio, and has received personal/speaker fees from Allergan/Tobira, Genfit SA, Gilead, Kenes, and BMS outside the submitted work; Vlad Ratziu has received personal fees for consultancy services from Intercept; Stephen Harrison has consulted/advised, holds stock ownership/equity from Akero, Galectin, Genfit, Madrigal, and Metacrine, has received grants from Axcella, Cirius, CymaBay, Galectin, Galmed, Genfit, Gilead, Hightide, Madrigal, NGM, Novartis, Novo Nordisk, Pfizer, and Second Genome, is a consultant/advisor for Albireo, Axcella, BMS, Cirius, Civi, CLDF, Consynance, Concept, CymaBay, Echosens, Galmed, Gilead, Hightide, HistoIndex, Innovate, IQVIA, Lipocine, Medpace, NGM, Novartis, Novo Nordisk, Perspectum, Pfizer, PPD, Prometheus, Proetric, Second Genome, and Terns, and is a member of the speakers bureau for AbbVie and Alexion; Arun J. Sanyal is President of Sanyal Bio, has stock options in Indalo, Durect, Tiziana, Exhalenz, and Northsea, is a consultant to Gilead, Allergan, Bristol-Myers Squibb, Pfizer, Merck, Galmed, Novartis, Novo Nordisk, Lilly, Siemens, Genentech, Boehringer Ingelheim, Glympse Bio, Genfit, Coherus, Surrozen, Poxel, 89 Bio, Perspectum, AstraZeneca, Medimmune, and Lipocine, and is an unpaid consultant to Intercept, Zydus, Echosens, Immuron, Madrigal, Galectin, Blade, Pliant, Albireo, and AMRA; Jörn M. Schattenberg has received grants and personal fees from Gilead Sciences, Boehringer Ingelheim, and Siemens Healthineers, and personal fees from Genfit, Intercept Pharmaceuticals, Novartis, Pfizer, and Roche outside the submitted work; A. Sidney Barritt has consulted for Intercept in the past 12 months, and is site Principal Investigator for clinical trials funded by Intercept; Mazen Noureddin has been on the advisory board for Gilead, Intercept, Pfizer, Novartis, Allergan, Blade, and Echosens North America, has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Novartis, Shire, and Zydus, and is a minor shareholder or owns stock in Anaetos and Viking; Martin Bonacci, Gail Cawkwell, and Bruce Wong are employees and stock shareholders of Intercept; Mary Rinella previously consulted for Intercept Pharmaceuticals, Inc, Gilead Sciences, Genfit, NGM Biopharmaceuticals, Enanta, Immuron, Fractyl, ProSciento, Gelesis, Merck, Bristol-Myers Squibb, Metacrine, Viking Therapeutics, Allergan, CymaBay, Boehringer Ingelheim, Sagimet, and Novartis. Funding Financial support for medical editorial assistance was provided by Intercept Pharmaceuticals, Inc.
Funding Information:
Funding Financial support for medical editorial assistance was provided by Intercept Pharmaceuticals, Inc.
Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - Background & Aims: Nonalcoholic steatohepatitis (NASH) affects patients’ health-related quality of life (HRQoL). Patient-reported outcomes (PROs) evaluating HRQoL were assessed in the RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) study, which showed that obeticholic acid (OCA) significantly improved fibrosis in patients with NASH. Methods: Noncirrhotic NASH patients in a phase 3, double-blind, randomized, placebo-controlled, multicenter, international study of OCA were enrolled. The Chronic Liver Disease Questionnaire–NASH and EuroQol EQ-5D-5L were administered at baseline, 6, 12, and 18 months. Results: There were 1218 patients (age, 54.1 ± 11.5 y; 57% women; 43% stage F3) in the expanded intent-to-treat population (stages, F1–F3) assigned randomly to 10 mg (N = 407) or 25 mg (N = 404) OCA or placebo (N = 407). Baseline measurements were balanced across treatment groups for EuroQol EQ-5D-5L and Chronic Liver Disease Questionnaire–NASH, including Itch score: 5.75 ± 1.53 (scale 1–7, with 7 representing no itching). Nineteen (1.6%) patients discontinued therapy (protocol mandated) because of grade 3 pruritus. Patients receiving 25 mg OCA experienced mild worsening of itch scores primarily in the first months of treatment: mean ± SE change from baseline –0.66 ± 0.12, –0.44 ± 0.12, and –0.42 ± 0.13 at 6, 12, and 18 months, respectively (all P < .01). No other PRO worsening was associated with 25 mg OCA. Patients experiencing fibrosis improvement, Nonalcoholic Fatty Liver Disease Activity Score decrease (by ≥2 points), or NASH resolution had greater PRO improvements in some domains. Conclusions: NASH patients evaluated in REGENERATE had impaired quality of life and underlying pruritus at baseline. Improvement of NASH corresponded with improvement in several HRQoL domains. Generally mild pruritus occurs early after OCA therapy initiation and does not worsen over time. ClinicalTrials.gov: NCT02548351.
AB - Background & Aims: Nonalcoholic steatohepatitis (NASH) affects patients’ health-related quality of life (HRQoL). Patient-reported outcomes (PROs) evaluating HRQoL were assessed in the RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) study, which showed that obeticholic acid (OCA) significantly improved fibrosis in patients with NASH. Methods: Noncirrhotic NASH patients in a phase 3, double-blind, randomized, placebo-controlled, multicenter, international study of OCA were enrolled. The Chronic Liver Disease Questionnaire–NASH and EuroQol EQ-5D-5L were administered at baseline, 6, 12, and 18 months. Results: There were 1218 patients (age, 54.1 ± 11.5 y; 57% women; 43% stage F3) in the expanded intent-to-treat population (stages, F1–F3) assigned randomly to 10 mg (N = 407) or 25 mg (N = 404) OCA or placebo (N = 407). Baseline measurements were balanced across treatment groups for EuroQol EQ-5D-5L and Chronic Liver Disease Questionnaire–NASH, including Itch score: 5.75 ± 1.53 (scale 1–7, with 7 representing no itching). Nineteen (1.6%) patients discontinued therapy (protocol mandated) because of grade 3 pruritus. Patients receiving 25 mg OCA experienced mild worsening of itch scores primarily in the first months of treatment: mean ± SE change from baseline –0.66 ± 0.12, –0.44 ± 0.12, and –0.42 ± 0.13 at 6, 12, and 18 months, respectively (all P < .01). No other PRO worsening was associated with 25 mg OCA. Patients experiencing fibrosis improvement, Nonalcoholic Fatty Liver Disease Activity Score decrease (by ≥2 points), or NASH resolution had greater PRO improvements in some domains. Conclusions: NASH patients evaluated in REGENERATE had impaired quality of life and underlying pruritus at baseline. Improvement of NASH corresponded with improvement in several HRQoL domains. Generally mild pruritus occurs early after OCA therapy initiation and does not worsen over time. ClinicalTrials.gov: NCT02548351.
KW - Chronic Liver Disease
KW - NASH
KW - Patient-Reported Outcomes
KW - Pruritus
UR - http://www.scopus.com/inward/record.url?scp=85116434732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85116434732&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.07.020
DO - 10.1016/j.cgh.2021.07.020
M3 - Article
C2 - 34274514
AN - SCOPUS:85116434732
SN - 1542-3565
VL - 20
SP - 2050-2058.e12
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 9
ER -