Primary biliary cholangitis: obeticholic acid continues to reduce cholestasis markers


  • International Clinical Digest
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Takeaway

  • For patients with primary biliary cholangitis (PBC), obeticholic acid (Ocaliva, Intercept Pharmaceuticals) leads to prompt and sustained improvement in cholestasis markers and hepatic enzymes. 
  • 2 additional studies of the drug are underway.

Why this matters

  • Obeticholic acid may be helpful for patients who respond inadequately to ursodeoxycholic acid (Actigall, Allergan).

Key results

  • About half of all patients had responded at both months 12 and 48.
  • Obeticholic acid led to greater change to alkaline phosphatase vs baseline at all time points; for example:
    • 12 months: −105.2 U/L; P<.0001.>
    • 48 months: −95.6 U/L; P<.0001.>
  • Other significant drops with obeticholic acid vs placebo included total bilirubin; gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase, which began falling at month 3; C-reactive protein; antibodies.
  • IL-12 and fibroblast growth factor-19 rose.
  • Slight drop in estimated risk for all-cause death or transplantation at 12 and 48 months. 
  • No serious adverse events or new safety signal.

Study design

  • 3-year interim analysis of open-label extension of POISE trial (n=193).
  • Trial randomly assigned adults with PBC to various obeticholic acid doses vs placebo.
  • Outcome: changes vs baseline in laboratory measures.
  • Funding: Intercept Pharmaceuticals.

Limitations

  • Outcomes were surrogates; clinical outcome rates were estimates.