Combination therapy of mycophenolate mofetil and ursodeoxycholic acid for the treatment of patients with incomplete response to ursodeoxycholic acid in primary biliary cirrhosis

Liling ZHAO; Zhilei CHEN; Fengchun ZHANG

ABSTRACT

Objective:

To observe the efficacy of mycophenolate mofetil (MMF) combined with ursodeoxycholic acid (UDCA) for the treatment of primary biliary cholangitis (PBC) with incomplete response to UDCA monotherapy.

Methods:

This is an open label study. Combination therapy of MMF (0.75-1.5 g/d) and UDCA (13-15 mg·kg -1·d -1) were applied to PBC patients with incomplete response to UDCA alone according to Barcelona Criteria. The expected observation duration of treatment were at least 12 months. The levels of serum alanine amiotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), albumin (Alb), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (GGT), immunoglobulin (Ig)M, IgG, IgA were mea-sured at different time points before and after treatment. The biochemical response rates were evaluated with reference to formerly reported criteria including Barcelona criteria and so on. Paired student's t-test and wilcoxon matched-pairs signed rank test were used to compare differences between groups before and after treatment. Mann-Whitney U test was used to compare differences between the two independent groups with abnormal distribution. A two-sided P<0.05 was considered statistically significant.

Results:

Seventeen of 29 patients included were treated with combination therapy for at least 1 year. The levels of serum ALP were significantly decreased after 3 months [(369±184) U/L vs (309±148) U/L, t=2.149, P=0.045] but not afterwards. GGT levels were significantly decreased at 6 months [266.5(205.5, 414.0) U/L vs 217.5(173.8, 391.8) U/L, Z=-2.334, P=0.018] and the significance continued to 1 year. IgM, IgG and IgA levels had a significant decrease at 3, 6 and 12 months but not AST, Tbil or Alb levels. The biochemical response rates were between 9.5%-23.5%.

Conclusion:

Overall, the biochemical response rate of combination therapy of MMF and UDCA is low in incomplete responders to UDCA alone. Early recognition of incomplete responders is of great im-portance and high quality researches are needed to confirm the effectiveness of the combined therapies.