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Combination therapy improves outcomes, pruritus in PBC

Long-term treatment with combination ursodeoxycholic acid and bezafibrate resulted in normalized alkaline phosphatase among more than 50% of patients with primary biliary cholangitis in a recently published study.

The combination therapy was most effective among those with lower fibrosis and severity of cholestasis, but provided complete or partial itching relief in most patients.

“The results of this prospective study demonstrate the long-term efficacy of adding bezafibrate to [ursodeoxycholic acid] in patients with PBC and suboptimal response to [ursodeoxycholic acid], and a clear-cut effect on pruritus,” Anna Reig, MD, from the University of Barcelona, Spain, and colleagues wrote. “Data on placebo-controlled trials under evaluation sustain these relevant clinical and biochemical positive effects in patients with PBC and in other chronic cholestatic conditions.”

The researchers enrolled 48 patients with PCB, including 28 who had participated in a previous study on the 1-year effect of bezafibrate therapy. The patients received treatment for an average 8.3 years (range, 3.5-13.7 years) with 13 mg/kg to 16 mg/kg per day of ursodeoxycholic acid (UDCA). However, their alkaline phosphatase (ALP) levels were still elevated to an average 2.4 (range, 1.9-3.5) times upper normal values.

After combination treatment with bezafibrate for a median 38 months (range, 22-50 months), ALP levels decreased to 1 (range, 0.7-1.6) times upper normal values in all patients. Twenty-six patients achieved normalized ALP within a median 4 months.

Patients who achieved normalized ALP were older (55 vs. 47.4 years; P < .01), had a lower prevalence of pruritus (42% vs. 78%; P < .01), lower levels of ALP (2 vs. 3.4 times upper normal values; P < .001) and cholesterol (253 vs. 280 mg/dL; P < .05), and fewer patients had bilirubin above 1.2 mg/dL, compared with patients with incomplete response.

Similarly, patients who achieved normalized ALP had higher serum albumin concentrations and lower liver stiffness according to elastography (6.3 vs. 10.7 kPa; P = .007) and were less likely to have aspartate aminotransferase to platelet ratio index above 0.54 (27% vs. 68%; P < .01) or GLOBE scores above 0.3 (19% vs. 50%; P = .02) than in patients with incomplete ALP response.

Among those who achieved normalized ALP, GLOBE scores improved from 0.46 at baseline (range, 0.76 to 0.18) to 1 (range, 1.52 to 0.45; P < .001) and the median 5, 10 and 15 UK-PBC scores improved from 0.95% to 0.65%, from 3.2% to 2.2%, and from 5.95% to 4.05%, respectively, (P < .01).

For the 26 patients who reported pruritus before bezafibrate therapy, itching disappeared completely for 16 patients and partly for 7 patients, representing a significant alleviation of pruritus according to visual analog score from 3.7 (range, 1.2-5.6) to 0 (range, 0-1.4; P < .0001). However, discontinuation of bezafibrate in patients with mild or no pruritus showed an increase or recurrence of itching from 0 (range, 0-0.8) to 4.6 (range, 3.7-6.5; P = .001). Itching decreased or disappeared after resuming bezafibrate therapy.

The researchers observed no instances of liver decompensation, death or transplantation among patients who achieved normalized ALP and no patients experienced severe adverse events during treatment – by Talitha Bennett

Disclosure: Reig reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.