Budesonide in autoimmune liver disease: treatment response in a large real life cohort

Abstract

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disorder that leads to end stage liver disease if left untreated. The standard therapeutic regimen consists of prednisolone in combination with azathioprine. AIH generally responds well to immunosuppressive treatment, yet many patients suffer from steroid-specific side effects. Budesonide (a steroid with a high hepatic first-pass metabolism) is an alternative drug and was shown to be effective in inducing and maintaining remission with few steroid-specific side effects (Manns et al. 2010 Gastroenterology). We here report real life data of a large cohort of patients treated with budesonide at our liver unit. Methods: A total of 80 patients (64 AIH and 16 overlap) were identified who had received budesonide. Start of treatment was with 9 mg per day and the mean maintenance dose of budesonide was 6.2 mg. Initial immunosuppressive treatment included azathioprine in 49 patients patients, MMF in 6 patients and tacrolimus in 1 patient. Patients were evaluated at 6, 12, 24 and 36 months. Reasons for changing the therapeutic regimen to budesonide were recorded. Treatment response was defined as normal serum levels of aminotransferases. This was chosen in order to be able to compare the results with the published study results. Results: 80 patients had received budesonide treatment for a mean of 27.3 months. Of the patients included in this study, 37 (46%) were given budesonide due to steroid-specific side effects, 32 (40%) because of a steroid-dependent course of disease and 11 (14%) patients as initial therapy. In total, 25% of the patients were in biochemical remission when budesonide treatment was initiated. After 6, 12, 24 and 36 months, 53%, 67%, 75% and 67% of patients achieved a biochemical remission and serum ALT levels were significantly reduced at all time points analysed (p < 0.004). Patients, who were given budesonide due to steroid-specific side effects, responded in 47% after 6 months, in 66% after 12 months, in 92% after 24 months and in 75% after 36 months of treatment. Patients with a steroid dependent course achieved normal AST and ALT levels in 56% after 6 months, in 71% after 12 months, in 55% after 24 months and in 67% after 36 months. The group of patients who were administered on budesonide as initial therapy responded in 50% after 6 months, in 85% after 12 months, in 67% after 24 months and in 25% after 36 months. We identified 13 patients with a steroid-induced osteopenia at the beginning of budesonide treatment. In follow up DXA we saw improvement in 5 patients, stable results in 5 patients, worsening in 1 patient and 2 patients had no follow up measurement. 18 patients were treated with budesonide alone, including 8 patients with an AIH/PBC overlap. Overlap patients seemed to respond favourably to budesonide treatment with 75% reaching remission after 6 months compared to only 40% of AIH patients. Conclusion: The treatment of AIH is highly individual as is the course of disease. Budesonide as part of a combination therapy is effective in inducing and maintaining remission for some patients. Patients with an overlap syndrome respond favourably to budesonide treatment and budesonide monotherapy may be sufficient in some of these patients. Corresponding author: Peiseler, Moritz E-Mail:moritz.peiseler@gmx.de