S2577 PBC Without Biochemical Remission. What Is the Role of Obeticholic Acid?

Introduction: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease associated with high levels of alkaline phosphatase (ALP) and total bilirubin (TB). PBC can progress to cirrhosis with need for transplantation. Ursodeoxycholic acid (URSO) is the first line agent for PBC, but some require another agent to achieve biochemical remission. The second line therapy, Obeticholic acid (OCA), was recently voted against approval by the Food and Drug Administration (FDA) due to unfavorable risk-benefit. We aimed to evaluate patients on OCA therapy and whether biochemical response was achieved to help guide future management if this agent may not be accessible. Methods: A retrospective study of PBC patients was conducted using Slicer Dicer within Epic. Criteria was narrowed to those currently on OCA therapy or those who recently discontinued. Data included most recent ALP and TB while on OCA therapy to determine biochemical response to treatment. Biochemical remission was defined as achieving a normal ALP and TB 0.6 times the upper limit of normal, biochemical improvement as improvement in ALP levels, and non-response as those without biochemical improvement nor remission. Concomitant use of URSO and fibrates were recorded. Results: Overall, 286 patients with PBC were identified of which 19 are on OCA therapy and 9 recently discontinued due to intolerance or unclear benefit. The average duration of therapy was 1,375 days or 3.7 years with a range of 279-2,655 days. 73.7% (n = 15) are biochemical non-responders. Four patients are currently on OCA monotherapy due to URSO intolerance. Of these, 75% (n = 3) are non-responders. Twelve patients (63.1%) on URSO and OCA are on combination therapy of which 91.6% (n = 11) have not achieved biochemical remission. Three patients are on triple therapy with URSO, OCA and a fibrate of which 2 achieved biochemical remission. Two patients (50%) achieved biochemical improvement on OCA monotherapy and 6 patients (50%) on URSO + OCA. One patient on triple therapy achieved neither biochemical improvement nor remission. Conclusion: Achieving biochemical remission is associated with decreased progression of PBC. OCA has been the only second line therapy available to patients with PBC intolerant to URSO or with suboptimal response. Although most patients on OCA have still not achieved biochemical remission, 10 out of 19 patients did have biochemical improvement. The loss of this agent could be detrimental, especially for patients in biochemical remission and those already on fibrate therapy.