Original article
Pancreas, biliary tract, and liver
Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

https://doi.org/10.1016/j.cgh.2017.06.001Get rights and content

Background & Aims

Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH.

Methods

We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC.

Results

There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal.

Conclusions

Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

Section snippets

Study Design

We collected data from patients with an established AIH diagnosis from 19 centers across Europe, the United States, Canada, and China. AIH was diagnosed based on a combination of autoimmune serology, serum γ globulin or IgG levels, and compatible liver biopsy findings.17 Overlaps of AIH with primary biliary cholangitis and primary sclerosing cholangitis were classified according to suggested international guidelines.18 All patients who were treated with second-line agents were identified.

Characteristics of the Patient Population

The medical records of 2260 patients with AIH were evaluated. Among 302 identified AIH patients treated with second-line agents, 171 received MMF, 114 received tacrolimus, 12 received cyclosporine, 2 received everolimus, and 1 patient each received cyclophosphamide, rituximab, or methotrexate. The final study group included 201 AIH patients, 121 received MMF and 80 received tacrolimus (Figure 1). The number of cases from each participating center is presented in Supplementary Table 1.

All

Discussion

For the significant number of AIH patients who do not tolerate or have a suboptimal response to SOC therapy, the future holds a risk for cirrhosis, liver failure, liver transplantation, or death.20, 21, 22 Additional treatment options beyond standard therapy with steroids and azathioprine therefore are needed. Over the years, several second-line options have been evaluated, but reports have been limited to small case series. This study represents a large cohort of patients exposed to

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  • Cited by (0)

    Conflicts of interest The authors disclose no conflicts.

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