Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy

Roberts, Stuart K.; Lim, Ricky; Strasser, Stephan; Nicoll, Amanda; Gazzola, Alessia; Mitchell, Joanne; Siow, Way; Khoo, Tiffany; Hamarneh, Zaki; Weltman, Martin; Gow, Paul J; Janko, Natasha; Tse, Edmund; Mishra, Gauri; Cheng, En-Hsiang; Levy, Miriam; Cheng, Wendy; Sood, Siddharth; Skoien, Richard; Mitchell, Jonathan; Zekry, Amany; George, Jacob; MacQuillan, Gerry; Wigg, Alan; Stuart, Katherine; Sievert, William; McCaughan, Geoffrey W.

doi:10.1016/j.cgh.2017.09.063

Cited by 42 publications

(46 citation statements)

References 33 publications

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“…Patients with AIH who fail AZA have limited rescue options with the most frequently used second line treatment being mycophenolate mofetil. The success rate of TG therapy in our cohort was slightly higher compared to mycophenolate mofetil for those patients who switched due to intolerable side effects (85% vs 43%‐75%) or due to insufficient response on conventional thiopurines (50% vs 20%‐34%) . A multicentre study with a considerable experience in AIH patients (n = 105) treated with mycophenolate mofetil reported 25% tolerable and 9% intolerable side effects, which is comparable to our data in patients using TG .…”

Section: Discussionsupporting

confidence: 80%

Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands

Brand

Nieuwkerk

Verwer

et al. 2018

Aliment Pharmacol Ther

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SummaryBackgroundAzathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid‐sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to these regimens.AimTo evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.MethodsRecords of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first‐line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.ResultsNo serious adverse events occurred in patients treated with TG during a median follow‐up of 18 months (range 1‐194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty‐eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non‐response (n = 2). TG was effective in all AIH patients as first‐line maintenance treatment.ConclusionIn our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.

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Section: Discussionsupporting

confidence: 80%

Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands

Brand

Nieuwkerk

Verwer

et al. 2018

Aliment Pharmacol Ther

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“…Five studies (n = 309) specified response rates in each subgroup (intolerance and nonresponse) . Pooled response rate in the subgroup of patients with intolerance to standard of care was 0.82 (95% CI 0.77‐0.87) and pooled response rate among nonresponders was 0.32 (95% CI 0.24‐0.39), I 2 = 0% (Figures and ).…”

Section: Resultsmentioning

confidence: 99%

“…Nine studies used the current definition of biochemical response according to the 2010 AASLD guidelines, in which normalisation of liver enzymes needs to occur for a complete response . Pooled response rate in this subgroup was 0.59 (95% CI 0.54‐0.64) (Figure S7).…”

Section: Resultsmentioning

confidence: 99%

“…Most common adverse events reported were gastrointestinal symptoms (nausea, vomiting, diarrhoea) in 34 patients, cytopenias in 10, dermatologic complaints (hair loss and rash) in seven and headache in four patients. Death was reported by one study only, in a patient who had Child‐Pugh C cirrhosis and developed severe sepsis with multiorgan failure from necrotising fasciitis …”

Section: Discussionmentioning

confidence: 99%

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

Santiago

Schwartz

Tamariz

et al. 2019

Aliment Pharmacol Ther

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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.

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“…However, in non-responders, tacrolimus led to a complete response in a significantly greater proportion of patients as compared with MMF (56.5% vs 34%, respectively). In a second retrospective study of 105 patients with AIH, Roberts et al found no differences in the proportion of patients who achieved biochemical remission within the first 2 years of treatment between patients receiving MMF for non-response and those who were intolerant to standard therapy (57% vs 62%, respectively) 24. Reduced biochemical remission rates and higher infection rates were however reported in cirrhotics receiving MMF as compared with non-cirrhotics.…”

Section: Second-line Therapymentioning

confidence: 97%

Autoimmune hepatitis and complexities in management

Janmohamed

Hirschfield

2018

Frontline Gastroenterol

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Autoimmune hepatitis (AIH) is a rare heterogenous immune-mediated liver disease that for the majority has effective therapy, usually resulting in excellent prognosis. Treatment is based on immunosuppression using standard therapy with corticosteroids and azathioprine. Second-line therapeutic options exist for those who are non-responders (‘difficult to treat AIH’) or intolerant to standard therapy; however, their use is not standardised, and in addition, there is vast variation in practice and efficacy. Given the rarity of AIH, expertise in its management can be limited to large referral programmes. In this case-based review, we aim to discuss common clinical dilemmas encountered by clinicians managing adult patients with AIH and address the related competencies in the 2010 Gastroenterology curriculum.

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Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy

Cited by 42 publications

References 33 publications

Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands

Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands

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

Autoimmune hepatitis and complexities in management

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