World Congress at ACG2017

Simultaneous Plenary Session 4A: Liver

60 - Effect of Obeticholic Acid Treatment in Patients With Primary Biliary Cholangitis on Categorical Shifts in GLOBE Score

Wednesday, October 18
9:40 AM - 9:50 AM
Location: Valencia Ballroom BC (Level 4)

Category: Liver       

Maren H. Harms, PhD1, Willem J. Lammers, PhD2, Bettina E. Hansen, MSc, PhD3, Marlyn J. Mayo, MD4, Albert Pares, MD, PhD5, Elizabeth Smoot Malecha, PhD6, Richard Pencek, PhD6, Leigh MacConell, PhD6
1Erasmus University Medical Center, Rotterdam, Zuid-Holland, Netherlands; 2Erasmus University Medical Centre, Rotterdam, Zuid-Holland, Netherlands; 3University of Toronto, Toronto, ON, Canada; 4UT Southwestern Medical Center, Dallas, TX; 5University of Barcelona, Barcelona, Spain; 6Intercept Pharmaceuticals, Inc., San Diego, CA
Introduction: The Global PBC Study Group have developed and validated the GLOBE score: a prognostic algorithm (calculated from: age, ALP, total bilirubin, platelets and albumin) to predict risk of liver transplantation and all-cause mortality ( A GLOBE score ≤0.3 is associated with a liver transplant-free survival similar to that of a sex and age matched normal population, whereas a GLOBE score >0.3 is associated with significantly diminished liver transplant-free survival. POISE was a placebo-controlled, double-blind, 12-month Phase 3 study which assessed the efficacy of daily 5-10 mg obeticholic acid (OCA) in patients with PBC. The aim of this analysis was to use data from POISE trial to assess if OCA treatment had an effect on categorical shifts in the GLOBE score.

Methods: POISE inclusion criteria: PBC diagnosis, ALP ≥1.67x ULN and/or total bilirubin >ULN to < 2x ULN, stable UDCA dose or unable to tolerate UDCA. 216 patients were randomized and dosed with Placebo (PBO, n=73), OCA 5-10 mg (n=70; titration from daily 5 mg to 10 mg at month 6 based on response or tolerability), or OCA 10 mg (n=73). The GLOBE score was calculated at baseline and month 12 to assess disease progression.

Results: At baseline there were a similar number of patients across treatment groups who had a GLOBE score above or below 0.3. After 12 months of treatment, patients receiving OCA 5-10 mg (27%, p < 0.05) were significantly more likely to shift from above to below a GLOBE score of 0.3, as compared to PBO (6%). Additionally, after 12 months of treatment, more PBO patients (33%) compared to OCA-treated patients (OCA 5-10 mg: 13%, p= 0.06; OCA 10 mg: 3%, p < 0.01) progressed from a baseline GLOBE score below 0.3 to a GLOBE score above 0.3.

Discussion: OCA treatment resulted in a significantly greater number of patients achieving a GLOBE score ≤0.3, associated with survival that is similar to age and sex matched individuals as compared to PBO treatment. Also, fewer patients progressed to a GLOBE score >0.3, associated with diminished survival. These changes indicate a potential effect of OCA after only 12 months of treatment to delay disease progression in PBC patients who are insufficiently responding to UDCA; however, further evaluation is required. A Phase 3 study evaluating clinical outcomes with OCA in patients with PBC (COBALT) is ongoing to confirm the clinical benefit of OCA and may be used to test the utility of the GLOBE score with OCA.

Supported by Industry Grant: No

Citation: . EFFECT OF OBETICHOLIC ACID TREATMENT IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS ON CATEGORICAL SHIFTS IN GLOBE SCORE. Program No. 60. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.

Marlyn J. Mayo

UT Southwestern Medical Center
Dallas, Texas


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