Obeticholic acid cuts alkaline phosphatase levels in primary sclerosing cholangitis patients
Obeticholic acid (OCA) reduces serum concentrations of alkaline phosphatase (ALP) in patients with primary sclerosing cholangitis, a new study has found.
Researchers enrolled 76 patients into the phase II, randomized, double-blind, placebo-controlled trial. The placebo and 1.5–3-mg OCA groups each had 25 patients, while the 5–10-mg OCA arm had 26 patients. The treatment phase lasted for 24 weeks and was followed by a 2-year, long-term safety extension (LTSE) period. Study endpoints were changes in ALP and safety.
In the intention-to-treat population, 5–10-mg of OCA triggered a significant drop in serum ALP by week 24 as compared to placebo (least square [LS] mean difference, –83.42±40.34 U/L; p=0.043). The same was also observed by week 12 (LS mean difference, –82.35±33.39 U/L; p=0.017).
This effect was first observed by week 6 and persisted until week 24; however, uptitrating doses to 10 mg did not intensify the effect of OCA on serum ALP.
Moreover, in patients who continued OCA treatment, this reduction also persisted during the LTSE period. Among those who switched into OCA from placebo, drops in ALP emerged starting at the 6-month visit.
Serum ALP at week 24 in the OCA 1.5–3-mg group was not statistically different than in placebo comparators (p=0.067).
During the double-blind phase, majority of the patients receiving active treatment reported at least one treatment-emergent adverse events (TEAEs). Most were mild or moderate in severity, but severe TEAEs were more common in both OCA groups than in the placebo arm. There were 10 cases of serious TEAEs, only two of which occurred in the control group.