Bezafibrate for primary biliary cholangitis: A number needed to treat analysis

The clinical benefit of bezafibrate (BZF) in primary biliary cholangitis (PBC) has not been extensively quantified using absolute measures. We assessed the number needed to treat (NNT) with BZF to prevent liver transplantation (LT) or death (including liver-related death) in patients with PBC.

The NNT was calculated using LT-free survival probabilities among ursodeoxycholic acid (UDCA)-treated patients with PBC from the Dutch PBC Cohort Study and the reported adjusted hazard ratios (aHRs) for the effect of BZF on LT or death (aHR 0.33) and liver-related death (aHR 0.27) from the Japanese cohort study (Tanaka et al., J Hepatol 2021). The NNT to prevent one LT, death, or liver-related death within 5 years (NNT_5y) or 10 years (NNT_10y) was estimated.

In total, 2,271 (63.7%) patients with PBC had an alkaline phosphatase (ALP) level above the upper limit of normal (ULN) after 1 year of UDCA treatment. The median age was 57.1 years (IQR 50.1-67.0), 2,003 (88.2%) were female, and 187 (8.2%) had cirrhosis. Overall, the estimated NNT_5y and NNT_10y for BZF were 15 (95% CI 11-26) and 7 (95% CI 6-13), respectively, to prevent one LT or death, and 26 (95% CI 18-56) and 15 (95% CI 11-30), respectively, to prevent one LT or liver-related death. According to ALP category at one year of UDCA treatment (1.0-1.5 × ULN, 1.5-3.0 × ULN, and ≥3.0 × ULN), the NNT_5y to prevent one LT or death was 24 (95% CI 16-48), 12 (95% CI 9-23), and 7 (95% CI 5-15), respectively, while the corresponding NNT_10y values were 10 (95% CI 7-18), 7 (95% CI 5-13), and 4 (95% CI 3-8).

The projected efficacy of BZF, expressed as the NNT to prevent hard clinical endpoints, was substantial overall, including among patients with relatively favourable ALP levels (1.0-1.5 × ULN) after one year of UDCA treatment. These findings highlight the potential clinical benefit of off-label BZF in UDCA-treated patients without ALP normalisation.

Although infrequently used in hepatology, the number needed to treat (NNT) can increase awareness among clinicians and patients about the potential impact of second-line therapy. Bezafibrate showed strong efficacy (NNT <20) for preventing liver transplantation or (liver-related) death in people with primary biliary cholangitis, even in patients with relatively favourable alkaline phosphatase levels (1.0-1.5 × the upper limit of normal) after 1 year of ursodeoxycholic acid. Findings support the potential clinical benefit of off-label bezafibrate for patients who do not achieve alkaline phosphatase normalisation on ursodeoxycholic acid alone. The NNT facilitates shared decision-making between patients and physicians on the use of second-line therapy in people with primary biliary cholangitis.