A new meta-analysis published in Frontiers in Pharmacology evaluated second-line treatments for primary biliary cholangitis (PBC) and found that different therapies may each offer advantages for biochemical response, alkaline phosphatase (ALP) normalization and relief from pruritus (persistent itching). A 10 mg dose of seladelpar emerged as having the most balanced overall profile.
For the analysis, researchers analyzed 12 randomized controlled trials involving 1,540 adults with PBC who had an inadequate response or intolerance to the first-line therapy for PBC, ursodeoxycholic acid (UDCA).
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The studies evaluated several newer or second-line treatments, including bezafibrate, seladelpar, elafibranor, saroglitazar, linerixibat and obeticholic acid (OCA), which was withdrawn from the U.S. market last year.
Researchers looked at several measures of treatment effectiveness, including whether patients achieved a biochemical response based on changes in alkaline phosphatase (ALP) and bilirubin. They also looked separately at whether ALP levels returned completely to the normal range, as well as changes in pruritus and serious adverse events.
Bezafibrate ranked highest for achieving the study’s overall biochemical response criteria. Elafibranor 80 mg and seladelpar 10 mg also performed significantly better than placebo plus UDCA for this measure.
For complete normalization of ALP, seladelpar 10 mg ranked highest, closely followed by bezafibrate. OCA 10 mg did not significantly increase the likelihood of complete ALP normalization compared with placebo.
The treatments also differed in their effects on itching, which can significantly affect quality of life for people with PBC. Seladelpar 10 mg and 200 mg were associated with improvements in pruritus, as was linerixibat 40 mg. In contrast, OCA 10 mg was associated with worsening pruritus compared with placebo.
Learn more about pruritus: “How to manage intense itching, a common symptom of PBC”
Seladelpar 10 mg had a favorable serious adverse event profile, while OCA 5 to 10 mg had the highest risk of complications.
When efficacy, symptom relief and safety were considered together, seladelpar 10 had the most favorable overall profile, the researchers reported.
“By achieving high rates of complete ALP normalization while concurrently relieving pruritus and maintaining a robust safety record, seladelpar represents a major advancement in the pursuit of both prolonging transplant-free survival and restoring quality of life in patients with PBC,” they concluded.
The researchers cautioned that the analysis has limitations. Because there are few head-to-head trials comparing these treatments with one another, many of the comparisons were indirect. Differences between the studies, including treatment duration and patient characteristics, could also affect the findings.
