Systematic review with meta‐analysis: mycophenolate mofetil as a second‐line therapy for autoimmune hepatitis

Abstract

Background: First-line treatment for autoimmune hepatitis (AIH) typically includes corticosteroids in combination with azathioprine. Mycophenolate mofetil (MMF) is often used as a rescue therapy in patients who are intolerant of, or nonresponsive to, standard therapy. Aim:To systematically review studies and perform a meta-analysis on the efficacy and safety of MMF as a second-line therapy for AIH patients.Methods: MEDLINE, EMBASE and Cochrane Central were searched for studies that reported data on efficacy and safety of MMF as a second-line therapy in AIH. We calculated the pooled response rate, adverse events rate and discontinuation rate due to side effects, with their corresponding 95% confidence intervals.Results: Twelve studies comprising 397 patients, followed for a median of 34 months (range, 12-47 months), were included. MMF doses ranged from 0.5-4.0 g/d. Pooled response rate was 0.58 (95% CI 0.54-0.63). Pooled adverse events rate was 0.14 (95% CI 0.11-0.17), and pooled discontinuation rate due to side effects was 0.08 (95% CI 0.06-0.11). Five studies (n = 309) specified response rates according to reason for using MMF. Pooled response rate in the subgroup with intolerance to standard therapy was 0.82 (95% CI 0.77-0.87) and pooled response rate among nonresponders was 0.32 (95% CI 0.24-0.39). Conclusions:The overall efficacy of MMF as second-line therapy in AIH was high.Response rate was greater in patients who started the medication due to intolerance to standard therapy as opposed to nonresponse. Overall, MMF was well tolerated, with a low discontinuation rate due to side effects.Additional supporting information will be found online in the Supporting Information section at the end of the article.How to cite this article: Santiago P, Schwartz I, Tamariz L, Levy C. Systematic review with meta-analysis: mycophenolate mofetil as a second-line therapy for autoimmune hepatitis.

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

“…MMF has been given to patients with AIH who are intolerant of AZA or have an incomplete response or treatment failure with glucocorticoid/ AZA. In a meta-analysis involving five studies and 309 patients, (425) the pooled overall response rate was 58% (82% for AZA intolerance and 32% for treatment failure). MMF-based therapies were well tolerated, with a pooled adverse event rate of 14%, leading to discontinuation in 8%.…”

Autoimmune Hepatitis: 2019 Update

“…Recent systematic reviews demonstrated the overall efficacy of MMF as second-line therapy in AIH, with a low discontinuation rate due to side effects. 48,49 Other second-line treatments used by experts include tacrolimus and cyclosporine, and sirolimus, infliximab, and rituximab. 45 Since B-cells play a significant role in the pathogenesis of AIH, B cell depletion is a promising strategy for the management of AIH.…”

Liver Disease in Pregnancy: What's New

“…Due to the potential for negative health outcomes associated with antepartum and postpartum flares, it is important that AIH activity is monitored closely and is well controlled before and during pregnancy and in the early postpartum period. Standard AIH treatment consists of corticosteroids and azathioprine, although it is noted that mycophenolate mofetil is an acceptable alternative agent if standard therapy is not tolerated . Despite the lack of meta‐analyses and systematic reviews on AIH therapy in pregnancy, observational data about the use of corticosteroids and azathioprine in other immunologic diseases support the use of these therapies in AIH .…”