Budesonide for Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a chronic liver disease associated with excess morbidity and mortality. The mainstay of AIH therapy is prednisone plus azathioprine. However, both short-term and long-term use of prednisone can cause adverse effects. A potential alternate AIH treatment is budesonide, a steroid with high liver exposure but low systemic exposure that proved in a pilot study to be effective in previously untreated AIH patients.

Now, researchers have conducted an industry-supported, double-blind, randomized, controlled, multicenter, phase IIb trial of budesonide involving 203 noncirrhotic patients with AIH. In part one of the study, patients received azathioprine (1–2 mg/kg/day) plus either prednisone (40 mg daily, tapering to 10 mg) or budesonide (3 mg, 2–3 times daily) for 6 months. Patients who achieved complete biochemical response by 3 months — and, at the investigator's discretion, those not in remission by 6 months — could proceed to part two of the study, a 6-month, open-label segment in which all patients received azathioprine and budesonide.

At 6 months, more patients in the budesonide group than in the prednisone group achieved the primary endpoint: complete biochemical response (normalization of liver enzymes) and the absence of steroid-specific adverse effects, such as moon face, acne, buffalo hump, diabetes, and striae (47.0% vs. 18.4%; P<0.001); more patients in the budesonide group achieved complete biochemical response (60.0% vs. 38.8%; P=0.001), and fewer experienced steroid-specific adverse effects (28.0% vs. 53.4%; P<0.001). At 12 months, 95 (54.8%) of 173 patients who completed part two of the study achieved complete response; rates of complete response were similar between patients originally randomized to budesonide or prednisone.