Zobair M Younossi1, Maria Stepanova2, Harry L A Janssen3, Kosh Agarwal4, Mindie H Nguyen5, Ed Gane6, Naoky Tsai7, Issah Younossi2, Andrei Racila2. 1. Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org. 2. Center for Outcomes Research in Liver Disease, Washington, District of Columbia. 3. Toronto Centre for Liver Disease, University Health Network, Toronto, Canada. 4. Institute of Liver Studies, Kings College Hospital, London, United Kingdom. 5. Stanford University Medical Center, Palo Alto, California. 6. Auckland Clinical Studies, Auckland, New Zealand. 7. Queens Medical Center, University of Hawaii, Honolulu, Hawaii.
Abstract
BACKGROUND & AIMS:Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient-reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection. METHODS: We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017. In these trials, patients were treated with an approved oral antiviral regimen (tenofovir, entecavir, adefovir, lamivudine, or telbivudine) and then randomly assigned to groups given vesatolimod (an oral agonist of Toll-like receptor 7) or placebo. PROs were collected using the Short Form-36, the Chronic Liver Disease Questionnaire, and the Work Productivity and Activity Impairment: Specific Health Problem questionnaires before treatment and during treatment weeks 12, 24, and 48. RESULTS: We did not observe significant differences in PROs between patients receiving vesatolimod vs placebo. At baseline, patients with viral suppression (HBV DNA level, <20 IU/mL) had higher PRO scores (by up to +10.6% of a PRO range size). During treatment, there were significant increases in scores for some domains of the Chronic Liver Disease Questionnaire and in General Health scores of Short Form-36 (increases of up to 4.9%; P < .05). Patients with a decrease of at least 2.7 log10 IU/mL in level of HBV DNA had substantially larger increases in PRO scores (P < .05 for 10 of 22 studied PROs). In multivariate analysis, a reduction in viral load was independently associated with increases in PROs (β values up to 1.6% per log10 IU/mL decrease; P < .05). CONCLUSIONS: In an analysis of data from phase 2 trials, we associated active treatment of chronic HBV infection with increased PRO scores. These findings support inclusion of PRO end points in assessments of efficacy and safety in clinical trials of treatments for HBV infection.
RCT Entities:
BACKGROUND & AIMS:Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient-reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection. METHODS: We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017. In these trials, patients were treated with an approved oral antiviral regimen (tenofovir, entecavir, adefovir, lamivudine, or telbivudine) and then randomly assigned to groups given vesatolimod (an oral agonist of Toll-like receptor 7) or placebo. PROs were collected using the Short Form-36, the Chronic Liver Disease Questionnaire, and the Work Productivity and Activity Impairment: Specific Health Problem questionnaires before treatment and during treatment weeks 12, 24, and 48. RESULTS: We did not observe significant differences in PROs between patients receiving vesatolimod vs placebo. At baseline, patients with viral suppression (HBV DNA level, <20 IU/mL) had higher PRO scores (by up to +10.6% of a PRO range size). During treatment, there were significant increases in scores for some domains of the Chronic Liver Disease Questionnaire and in General Health scores of Short Form-36 (increases of up to 4.9%; P < .05). Patients with a decrease of at least 2.7 log10 IU/mL in level of HBV DNA had substantially larger increases in PRO scores (P < .05 for 10 of 22 studied PROs). In multivariate analysis, a reduction in viral load was independently associated with increases in PROs (β values up to 1.6% per log10 IU/mL decrease; P < .05). CONCLUSIONS: In an analysis of data from phase 2 trials, we associated active treatment of chronic HBV infection with increased PRO scores. These findings support inclusion of PRO end points in assessments of efficacy and safety in clinical trials of treatments for HBV infection.
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