Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

contrasting

confidence: 52%

Editorial: “real world data” of AIH—time to connect!

Hupa-Breier

Taubert

Jaeckel

et al. 2018

“…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%

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

Santiago

Schwartz

Tamariz

et al. 2019

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.

“…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 .…”

Section: Overviewmentioning

confidence: 99%

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

Czaja

2020

Background: Thiopurines in combination with glucocorticoids are used as first-line, second-line and maintenance therapies in autoimmune hepatitis and opportunities exist to improve and expand their use. Aims:To describe the metabolic pathways and key factors implicated in the efficacy and toxicity of the thiopurine drugs and to indicate the opportunities to improve outcomes by monitoring and manipulating metabolic pathways, individualising dosage and strengthening the response.Methods: English abstracts were identified in PubMed by multiple search terms. Fulllength articles were selected for review, and secondary and tertiary bibliographies were developed.Results: Thiopurine methyltransferase activity and 6-tioguanine (6-thioguanine) nucleotide levels influence drug efficacy and safety, and they can be manipulated to improve treatment response and prevent myelosuppression. Methylated thiopurine metabolites are associated with hepatotoxicity, drug intolerance and nonresponse and their production can be reduced or bypassed. Universal pre-treatment assessment of thiopurine methyltransferase activity and individualisation of dosage to manipulate metabolite thresholds could improve outcomes. Early detection of thiopurine resistance by metabolite testing, accurate estimations of drug onset and strength by surrogate markers and adjunctive use of allopurinol could improve the management of refractory disease. Dose-restricted tioguanine (thioguanine) could expand treatment options by reducing methylated metabolites, increasing the bioavailability of 6-tioguanine nucleotides and ameliorating thiopurine intolerance or resistance. Conclusions:The efficacy and safety of thiopurines in autoimmune hepatitis can be improved by investigational efforts that establish monitoring strategies that allow individualisation of dosage and prediction of outcome, increase bioavailability of the active metabolites and demonstrate superiority to alternative agents.