BOSTON, MA—Patients with primary biliary cholangitis and mild renal impairment responded to treatment with obeticholic acid (OCA), warranting further study in a larger sample of patients, according to authors of a post-hoc analysis of the Phase 3 POISE study. Their findings were presented at The Liver Meeting® 2016.
The primary composite endpoint of the POISE trial was an alkaline phosphatase level <1.67XULN; a ≥15% reduction in alkaline phosphatase; and a total bilirubin ≤ULN at Month 12, Paul J. Pockros, MD, Scripps Clinic, La Jolla, CA, noted.
Patients were randomized 1:1:1 to daily placebo, titration OCA (5–10mg) or OCA 10mg once daily for 12 months. (Those randomized to titration OCA initiated treatment at 5mg and up-titrated to 10mg if they did not achieve the primary endpoint and were tolerating therapy.) Renal function status was categorized by Cockcroft-Gault calculated creatinine clearance values: normal: >80; mild: >50–80; moderate: ≥30–50; and severe: <30 (mL/min).
Of 216 patients enrolled and dosed, none had severe renal impairment at baseline. Few patients were assigned to the moderate impairment group (3 placebo, 3 OCA 5–10mg, and 2 OCA 10mg), so mild and moderate group data were pooled for analysis, noted Dr. Pockros.
“A significantly greater proportion of OCA-treated patients achieved the primary endpoint regardless of renal function status,” noted Dr. Pockros. For patients with normal renal function, significantly more patients in both OCA groups did so than in the placebo group (P<0.0001 in each case); for patients with mild/moderate renal impairment, a significantly greater proportion of patients in the 10mg OCA achieved the primary endpoint than placebo (P<0.05).
Of 8 patients with moderate renal impairment, one of three (33%) in the placebo arm, one of three (33%) in the titration OCA 5-10mg arm, and none in the 10mg OCA arm met the primary endpoint.
The safety profile was similar across renal function status; pruritus was the most common AE. “There was no apparent effect of OCA on renal safety,” Dr. Pockros reported. “OCA was safe and well-tolerated regardless of renal status.”