Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Abstract

Summary Background Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre‐treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre‐treatment IgG levels.

Letter: elderly AIH patients—an important subgroup. Authors’ reply

“…We express our appreciation to Dr Fan et al for their interesting observations and questions relating to our study of mycophenolate mofetil (MMF) as a second-line therapy in autoimmune hepatitis that was refractory or intolerant of standard therapy. 1,2 We agree that our paper raises the question of how best to manage elderly patients (≥60 years), and whether MMF is safe and effective in this group. The data in our paper indicated that those with age >53 years had a significantly increased response to MMF: OR 25.3 (95% CI, 2.0-318).…”

Review article: opportunities to improve and expand thiopurine therapy for autoimmune hepatitis

“…Mycophenolate mofetil, a purine antagonist of different molecular structure and metabolism than the thiopurine drugs (Figure 1), 7,8,10 has been enlisted as a second‐line agent for azathioprine intolerance and nonresponse 187‐189,230 . MMF is hydrolysed by liver esterases to mycophenolic acid (MPA) which acts as a reversible inhibitor of IMPDH 7,8 .…”

Letter: elderly AIH patients—an important subgroup

“…1 We appreciate the novel and hard work of the authors. 1 We appreciate the novel and hard work of the authors.…”

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EDITORS,We read with great interest the article by Nicoll et al evaluating the predictors of response to mycophenolate mofetil (MMF) rescue therapy in patients with autoimmune hepatitis (AIH). 1 We appreciate the novel and hard work of the authors. This is the largest study to examine predictors of treatment response in AIH patients receiving MMF who have failed standard therapy.

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