studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 921A
Bruce E. Sill - Employment: Bristol-Myers Squibb; Stock Shareholder: Bristol-Myers
Squibb
Anupama Kalsekar - Employment: Bristol Myers Squibb
Yong Yuan - Employment: Bristol Myers Squibb Company
The following authors have nothing to disclose: Shalini Hede, Catherine St-Laurent
Thibault, Divya Moorjaney, Michael Ganz
1457
Hospitalisation for primary biliary cirrhosis: a UK-PBC
analysis of hospital episodes
Gideon Hirschfield 2 , Luke Vale 3 , Tracy J. Mayne 1 , George F.
Mells 4 , David Shapiro 1 , David Jones 5 ; 1 Intercept Pharmaceuticals,
San Diego, CA; 2 Centre for Liver Research, University of Birmingham,
Birmingham, United Kingdom; 3 Institute of Health & Society,
Newcastle University, Newcastle, United Kingdom; 4 Division of
Gastroenterology and Hepatology, Department of Medicine, University
of Cambridge, Cambridge, United Kingdom; 5 Institute of
Cellular Medicine, Newcastle University Medical School, Newcastle,
United Kingdom
Background: The advent of new therapies for patients with
primary biliary cirrhosis (PBC) highlights the need to understand
the current health burden of PBC. Objective: To assess
the frequency and nature of hospitalisations associated with
primary biliary cirrhosis (PBC). Methods: UK-PBC analysed all
records from 2009 through 2014 in the Hospital Episodes Statistics
database, containing information on all hospitalisation
across the National Health Service in England, where the ICD-
10 code for PBC (K74.3) appeared. We characterised primary
diagnosis for each hospitalisation. Results: There were 21,275
admissions with a PBC code over the 5-year observational
period covering 1631 unique ICD-10s listed as the primary
hospitalisation code. PBC was the primary code for 17% of
admissions. The number of relevant hospitalisations increased
from 3368 in 2009/2010 to 4995 in 2012/2014. The number
per 100,000 hospitalisations increased from 23 to 32 over
this period (Figure). The increase was almost completely driven
by the inclusion of PBC as a secondary diagnosis. Liver transplants
represented 5-10% of admissions with PBC as a primary
code, and 1- 2% of any PBC-related admission. The next 20
ICD-10 codes accounted for an additional 17% of admissions.
The top 20 codes included known sequelae of PBC: ascites
(2%), varices (2%), and liver cancer (1%). Remaining codes
included: anaemia (iron deficiency and unspecified) 3%; respiratory
(pneumonia, COPD and lower respiratory infections)
3%; osteoporosis and fractures 2%; and various abdominal
(unspecified abdominal pain, gastritis and gastroenteritis) 2%.
Conclusion: Our UK-PBC data confirms a significant clinical
need for patients with PBC, including a rising healthcare burden
from disease. The increase in PBC-related diagnoses may
be due to more accurate coding, greater co-morbidity as the
result of increased longevity, or may represent the true impact
of disease. New therapies preventing the progression of PBC to
end-stage cirrhosis, and its complications, may help to reduce
this rising burden.
Disclosures:
Tracy J. Mayne - Employment: Intercept Pharmaceuticals
David Shapiro - Employment: Inttercept Pharmaceuticals; Management Position:
Intercept Pharmaceuticals; Stock Shareholder: Intercept Pharmaceuticals
David Jones - Consulting: Intercept, Pfizer, Novartis; Speaking and Teaching:
Falk, Shire
The following authors have nothing to disclose: Gideon Hirschfield, Luke Vale,
George F. Mells
1458
Obeticholic Acid (OCA) has Incremental Efficacy in
Patients with Higher Baseline Alkaline Phosphatase
(ALP) Levels
Tracy J. Mayne, Richard Pencek, Tonya Marmon, David Shapiro;
Intercept Pharmaceuticals, Inc., San Diego, CA
Objective: Examine ALP lowering stratified by baseline ALP
among patients with primary biliary cirrhosis (PBC) treated with
10 mg OCA. Methods: We pooled data from the 10 mg treatment
arms of two phase 2 trials (n=20 and n=38) and one
phase 3 trial (n=73) randomized, double-blind, placebo-controlled
trials of OCA in patients with PBC. The percent change
in ALP at 3 months was calculated based on baseline ALP stratified
by 50 U/L. We ran a linear regression predicting percent
change in ALP based on baseline ALP. Results: As shown in the
first figure, both absolute and percent reduction in ALP were
greater at higher baseline ALP levels. As shown in the second
figure, for each incremental 100 U/L in baseline ALP, there
was an incremental 5% reduction in ALP at 3 months (intercept
= 17%) in patients treated with 10 mg OCA. Conclusion: A
standard measure of drug efficacy is percent reduction in a
specified marker. Statin efficacy is measured as percent reduction
in low density lipid cholesterol (LDL-C); blood pressure
medications are assessed by percent reduction in systolic and
diastolic blood pressure. At a fixed percent reduction, absolute
reduction in a biomarker will be greater with higher baseline
levels: a 50% reduction in LDL-C at a baseline of 200 mg/dL
is 100 mg/dL; a 50% reduction at 100 mg/dL is 50 mg/dL.
In the case of OCA, the percent reduction in ALP increases as
a function of baseline ALP. As shown by the regression model,
OCA produces an average 59% reduction at a baseline ALP
of 800 U/L, and an average 38% reduction at a baseline ALP
of 400 U/L. Achieved level of ALP has been shown to be associated
with improved progression-free survival (Lammers et al,
Gastroenterology 2014;147:1338). These data indicate that
patients with more progressed PBC, as measured by higher
serum ALP, may receive incremental benefit when treated with
OCA.