Real-World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis

Surain B Roberts; Marwa Ismail; Gowthami Kanagalingam; Andrew L Mason; Mark G Swain; Catherine Vincent; Eric M Yoshida; Cynthia Tsien; Jennifer A Flemming; Harry L A Janssen; Gideon M Hirschfield; Bettina E Hansen; Aliya F Gulamhusein; Canadian Network for Autoimmune Liver Disease

doi:10.1002/hep4.1518

Real-World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis

Hepatol Commun. 2020 Jul 6;4(9):1332-1345. doi: 10.1002/hep4.1518. eCollection 2020 Sep.

Authors

Surain B Roberts^{1

2}, Marwa Ismail¹, Gowthami Kanagalingam¹, Andrew L Mason³, Mark G Swain⁴, Catherine Vincent⁵, Eric M Yoshida⁶, Cynthia Tsien⁷, Jennifer A Flemming⁸, Harry L A Janssen¹, Gideon M Hirschfield¹, Bettina E Hansen^{1

2}, Aliya F Gulamhusein^{1

2}; Canadian Network for Autoimmune Liver Disease

Affiliations

¹ Toronto Centre for Liver Disease Toronto General Hospital University Health Network Toronto ON Canada.
² Institute of Health Policy, Management and Evaluation University of Toronto Toronto ON Canada.
³ Department of Medicine University of Alberta Edmonton AB Canada.
⁴ Department of Medicine University of Calgary Calgary AB Canada.
⁵ Département de Médecine Université de Montréal Montréal QC Canada.
⁶ Department of Medicine University of British Columbia Vancouver BC Canada.
⁷ Department of Medicine University of Ottawa Ottawa ON Canada.
⁸ Department of Medicine Queen's University Kingston ON Canada.

Abstract

Patients with primary biliary cholangitis (PBC) with incomplete response to ursodeoxycholic acid are at risk of disease progression and need additional therapy. Obeticholic acid (OCA) was approved in Canada in May 2017, but its effectiveness in a real-world setting has not been described. We sought to describe our experience with OCA in a Canadian cohort. OCA-naive patients treated at two Canadian centers were included. Clinical and biochemical data were collected at OCA initiation and during follow-up. Primary outcomes were changes in serum alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TB) over the duration of therapy. Secondary outcomes were changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin M (IgM), platelets, and albumin; and achievement of the primary endpoint of the original phase 3 study that led to OCA approval (A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis [POISE]), dose reductions, discontinuations, and tolerability. Repeated-measures models were used to assess changes in biochemistry over time. Sixty-four patients were included; 4 carried a diagnosis of overlap with autoimmune hepatitis. Mean age was 54.6 years, median ALP was 250 U/L, TB was 13 µmol/L, platelet count was 225 × 10⁹/L, and 24% had liver stiffness measurements ≥16.9 kPa. There was a significant reduction in mean ALP of 55 U/L (P < 0.001), GGT of 138 U/L (P < 0.001), ALT of 11.9 U/L (P < 0.001), AST of 5.7 U/L (P < 0.05), and IgM of 0.70 g/L (P < 0.001) over 12 months; TB remained stable (P = 0.98). Forty-four patients met POISE-inclusion criteria, 39% (n = 17) of whom had 12-month biochemical measurements. In this subset, 18% (n = 3/17) met the 12-month POISE primary endpoint, but considering follow-up to 19 months, 43% achieved this target (n = 9/21). Pruritus was the most commonly reported complaint. Conclusion: Use of OCA was associated with improvement in biochemical surrogates of outcome in PBC in a real-world setting.