Experience with obeticholic acid in patients with primary biliary cholangitis – multicentric Austrian analysis

The use of obeticholic acid (OCA) was recently approved as second line therapy for patients with primary biliary cholangitis (PBC) with insufficient response or intolerance to ursodeoxycholic acid (UCDA).

Aim:

To assess the efficacy and safety of obeticholic acid as second line therapy by patients with PBC (as monotherapy or add-on to UCDA).

Methods:

Our study included 28 PBC patients (89.2% women) with a mean age of 61.1 ± 10.1 years from 7 Austrian centers (Klagenfurt, Villach, Salzburg, Linz, Vienna, Eisenstadt and Innsbruck), who received therapy with obeticholic acid because of intolerance or insufficient response under the maximal dose of UCDA (14.2% monotherapy with OCA, 85.8% combination therapy OCA + UCDA). We evaluated the response of alkaline phosphatase (AP), alanine transaminase (ALT), gamma-glutamyltransferase (GGT) and bilirubin under the therapy with OCA. Furthermore, adverse events were assessed.

Results:

The median follow up of therapy with OCA was 10.5 months (between 0.5 and 24 months).

A significant reduction of AP, GGT and ALT was observed under the therapy with obeticholic acid (Table).

Tab. 1

	Baseline values (n = 28)	Values after 1 month of therapy (n = 27)	Values after 3 months of therapy (n = 23)	Values after 6 months of therapy (n = 22)	Values after 12 months of therapy (n = 14)	p value
AP (U/l) Median (IQR)	224 (188 – 283)	185 (160 – 253)	160 (141 – 225)	141 (115 – 200)	131 (92 – 140)	p < 0.05 between Baseline and 3, 6, 12 months of therapy
GGT (U/l) Median (IQR)	170 (108 – 330)	97 (45 – 194)	79 (43 – 146)	75 (41 – 163)	29 (19 – 43)	p < 0.05 between Baseline and 3, 6, 12 months of therapy
ALT (U/l) Median (IQR)	51 (30 – 63)	32 (27 – 48)	33 (23 – 46)	33 (25 – 44)	24 (20 – 28)	p < 0.05 between Baseline and 1, 3, 6, 12 month of therapy
Bilirubin (mg/dl) Median (IQR)	0.7 (0.53 – 1.10)	0.67 (0.5 – 1)	0.53 (0.44 – 0.71)	0.57 (0.40 – 1.02)	0.46 (0.41 – 0.53)	p < 0.05 between Baseline and 12 month of therapy

Adverse events were observed in 15/28 (53.5%) of patients. The following adverse events were recorded: pruritus 9/28 (32.1%), fatigue 4/28 (14.2%), joint pain 4/28 (14.2%), abdominal pain 2/28 (7.1%), peripheral edema 1/28 (3.5%), nausea 1/28 (3.5%), exanthem 1/28 (3.5%), and generalized musculoskeletal pain 1/28 (3.5%) of patients.

The treatment was stopped in 6/28 (21.4%) patients: in one case because of increase of AP and bilirubin after 7 months of therapy and in 5 cases because of adverse events (pruritus -2 cases, severe joint pain and peripheral edema – 1 case, exanthem-1 case and generalized musculoskeletal pain-1 case). One patient was lost from follow-up.

Conclusion:

The therapy with obeticholic acid is effective and relatively safe in patients with PBC.