Response to OCA in patients with PBC has previously been assessed according to the POISE score, defined as a reduction in alkaline phosphatase (ALP) to 1.67 times the upper limit of normal (ULN), at least a 15% reduction in ALP, and normalization of total bilirubin, said Conrado Fernandez-Rodriguez (University Hospital Foundation Alcorcón, Madrid, Spain).

But he pointed out that it is now recognized that complete response – normal ALP and total bilirubin of no more than 0.6 times the ULN – is associated with improved liver-related and overall survival.

“However, the effectiveness of long-term second-line therapy for this target is still uncertain,” he told delegates at The Liver Meeting 2023, held in Boston, Massachusetts, USA.

To investigate, Fernandez-Rodriguez and the IBER-PC cooperative group retrospectively assessed biochemical and POISE response in 311 Spanish and Portuguese patients with PBC who had failed to respond fully to 12 months of treatment with ursodeoxycholic acid and received second-line OCA. Of these, data were available for 258 patients at their 12-month follow-up and 176 patients at 2 years.

The participants were aged a mean of 56.6 years and 90.0% were women, with a mean disease duration of 8.2 years. Well-compensated cirrhosis (Child-Turcotte-Pugh score of A5–6) was reported in 21.2% of patients.

In all, 28.6% of patients were taking fibrate treatment; 44 before starting OCA treatment and 45 during.

Six-monthly analysis over a median follow-up of 26.3 months showed a notable biochemical response, said the presenter, with significant declines in levels of ALP and gamma-glutamyl transferase that continued beyond 2 years of treatment, and that were significantly greater among patients who were also taking fibrates.

There were also significant reductions in alanine transaminase and aspartate aminotransferase, although these plateaued after 2 years of treatment, and there was no increased benefit with fibrate treatment. Serum albumin levels increased significantly with OCA treatment but again there was no further benefit with the addition of fibrates.

Bilirubin levels decreased significantly, as did platelet count, immunoglobulin M, the international normalized ratio and cholesterol levels. However, there was no significant effect on liver stiffness, severity of liver disease (as measured by MELD score), the aspartate aminotransferase to platelet ratio index (APRI) score, or liver fibrosis.

Fernandez-Rodriguez highlighted that there was also a significant reduction in PBC-Globe and UK-PBC scores at 2 years, which predict the risk of being alive and free of liver failure at 3 and 5 years, respectively.

The overall rate of POISE response at 12 months was 44%. POISE response was sustained over time, with rates of 52.5% at 24 months and 62.8% at 36 months, and it was significantly associated with the absence of cirrhosis and a lower degree of cholestasis, the presenter noted.

Overall, the rate of POISE response was similar in patients taking and not taking fibrates, but Fernandez-Rodriguez pointed out that “patients on triple therapy were more likely to achieve a complete biochemical result compared to dual therapy.”

Multivariate analysis confirmed that POISE response at 12 months was significantly more likely in patients receiving triple rather than dual therapy and in those with lower bilirubin levels. Triple therapy also increased the likelihood of a maintained POISE response along with a lower degree of cholestasis (based on bilirubin and ALP levels), being female versus male, and the absence of cirrhosis. For a sustained complete biochemical response, triple therapy and a lower degree of cholestasis were the key significant predictive factors.

Adverse events occurred in 40.2% of patients and “the vast majority of them were mild,” said Fernandez-Rodriguez. However, decompensation was seen in 5% of patients and 18% of patients discontinued OCA, with grade 3 pruritus being the most common reason, occurring in 5%.