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Aim Ursodeoxycholic acid (UDCA) is the licensed 1st-line therapy for Primary Biliary Cholangitis (PBC); a cholestatic liver disease that can lead to cirrhosis, transplantation and death. In patients intolerant of UDCA, or with inadequate response, Obeticholic Acid (OCA) (a farnesoid X receptor agonist) remains licensed in the UK. We reviewed its efficacy as 1st- and 2nd-line therapy.Method A retrospective cohort study was performed in Newcastle-upon-Tyne Hospitals Trust using our autoimmune database. Demographics, biochemistry and adverse events up to month 60 of treatment were collected.Results 22 patients received OCA as 1st-line therapy following UDCA intolerance (100% female, mean age at diagnosis 54.8 years (SD±9.6), mean treatment duration 24.5 months (SD±18.5), median baseline ALP 244.5 (IQR 238). There was a sustained percentage reduction of median ALP of >20% from month 6–36 ( table 1).At 6 months, 42% had ALP <1.67x upper limit of normal (ULN) and 21% achieved ALP normalisation. By 12 months, 66.7% had ALP of <1.67xULN with 21% having normal ALP.5 (22.7%) were OCA intolerant due to GI symptoms (3 patients (60%)), itch (1 patient (20%)) and arthralgia (1 patient (20%)). 7 patients (31.8%) required escalation of itch treatment.59 patients received OCA as 2nd-line therapy (91.5% female, mean age at diagnosis 49 (SD±10.6), mean treatment duration 36.4 months (SD±23.2), baseline median ALP 261 (IQR 120)). There was a sustained percentage reduction of median ALP from month 6–60 (table 1).At 6 months, 38.9% had ALP<1.67x ULN, with a further 6.8% having normal ALP. By 12 months, 51.9% had ALP<1.67xULN with normal ALP in 7.5%.14 (23.7%) stopped OCA: non-response in 8 patients (57.1%) and itch in 3 patients (21.4%). 1 patient (7.1%) stopped OCA after developing nephrotic syndrome. 19 (32.2%) experienced new or worsening itch, all of whom were controlled with additional medication.Abstract P49 Table 1Median ALP and ALT with percentage change over time OCA: Obeticholic Acid, ALP: Alkaline Phosphatase,%: Percentage, M: MonthOCA as First line therapy Median ALP % Change Median ALT % Change Baseline 244.5 - 43.5 - M6 187 -23.5% 43 -1.1% M12 173 -29.5% 44 -21.8% M24 185 -24.3% 36 +19.5% M36 191.5 -21.6% 46.5 +6.7% M48 161.5 -33.4% 23.5 -45.9% M60 145.5 -40.5% 27.5 -36.8% OCA as Second Line therapy Median ALP % Change Median ALT % Change Baseline 261 - 46 - M6 217 -16.8% 32 -30.4% M12 192 -26.4% 31 -32.6% M24 182 -30.2% 29 -36.9% M36 170.5 -34.7% 32 -30.4% M48 159 -39.1% 25 -45.6% M60 158 -39.4% 24 -47.8% Discussion 1st- and 2nd-line therapy with OCA achieves sustained ALP reduction at 3 years of follow-up. Sustained ALT improvement was only achieved with 2nd-line therapy. OCA intolerance was similar between the groups with the commonest reasons for treatment termination being GI symptoms with 1st-line therapy and incomplete response with 2nd-line therapy. Approximately 1/3 of patients needed escalation of itch treatment.OCA is safe as1st- and 2nd-line therapy in PBC. Despite improvement in ALP with both 1st and 2nd-line therapy, approximately 40% didn’t reach the current treatment goal of ALP <1.67xULN by 1 year, emphasising the need for new therapies.