Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review

Deswal, Shivani; Srivastava, Anshu

doi:10.1016/j.jceh.2017.01.115

Cited by 16 publications

(27 citation statements)

References 41 publications

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“…It has been demonstrated that mycophenolate mofetil (MMF) ( 5 , 44 – 51 ), methotrexate ( 52 ), 6-mercaptopurine ( 53 ), allopurinol ( 54 , 55 ), tacrolimus ( 8 , 45 , 56 – 59 ) and everolimus ( 60 ) are effective and well-tolerated in patients with AIH. Torisu et al ( 61 ) indicated that UDCA monotherapy may be considered for treatment of patients with AIH with a serum ALT level of <200 IU/l.…”

Section: Discussionmentioning

confidence: 99%

Comparative efficacy and tolerability of treatments for adult autoimmune hepatitis: A systematic review and network meta‑analysis

et al. 2018

Exp Ther Med

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The most suitable treatment regimen for autoimmune hepatitis (AIH) in adults remains unknown and requires further investigation. The current study therefore aimed to integrate evidence to provide hierarchies of the comparative efficacies of treatments measured by clinical and biochemical remission. A Bayesian-framework network meta-analysis of randomized controlled trials (RCTs) was preformed to compare eight treatments for AIH. Eligible RCTs were identified by searching Embase, Pubmed and the Cochrane Library for publications between 1966 and April 2017. All outcomes were independently extracted from the included studies by two authors. A total of six RCTs were subsequently included in the current study. The network of comparisons on remission indicated that patients treated with prednisone (pred) experienced significantly increased rates of remission compared with those treated with azathioprine [AZA; odds ratio (OR), 0.21; 95% confidence interval (CI), 0.06–0.71] and budesonide (bude) + AZA significantly increased remission compared with placebo treatment (OR, 36.66; 95% CI, 1.40–962.49) or AZA (OR, 10.30; 95% CI, 1.50–70.70). Based on the cumulative ranking probabilities, bude + AZA (89.4) was ranked first, pred (69.1) was ranked second, pred + AZA (63.2) was ranked third and placebo (7.8) treatment was ranked last. Bude + AZA may be the most appropriate candidate for the treatment of non-cirrhotic patients. However, bude + AZA as frontline therapy for AIH requires more large-scale studies with a longer duration of follow-up histology and a focus on dose-response. Additionally, development of other prospective treatments, which may be used as alternative therapy or first line therapy, and their subsequent evaluation in clinical RCTs is required.

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Section: Discussionmentioning

confidence: 99%

Comparative efficacy and tolerability of treatments for adult autoimmune hepatitis: A systematic review and network meta‑analysis

et al. 2018

Exp Ther Med

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“…Interestingly, modulation of AZA metabolism to reduce side effects through co-administration of allopurinol was suggested and reported in small case series [68][69][70][71][72]. As side effects by this co-medication may be rather mild, this combinatory therapy should be further evaluated in RCTs.…”

Section: Purine Analogues: 6-mercaptopurine and 6-thioguaninementioning

confidence: 99%

Autoimmune Hepatitis: a Review of Established and Evolving Treatments

Bischoff

Yesmembetov

Antoni

et al. 2020

JGLD

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Autoimmune hepatitis (AIH) is a necroinflammatory liver disease commonly presenting with a fluctuating course of activity, presence of circulating autoantibodies, hyperglobulinemia of IgG, and/or response to immunosuppressive drugs. However, the disease displays a considerable heterogeneity. No single clinical or biochemical test may establish diagnosis of AIH. Thus, diagnosis still requires extensive clinical evaluation and experience. Prednisolone and azathioprine are considered standard treatment leading to remission in most patients. However, this standard treatment may not be effective in some patients or not be feasible due to one of these drugs. Over the past two decades additional immunosuppressant drugs for the treatment of AIH have been evaluated and have significantly extended the therapeutic spectrum. Among those novel drugs are mycophenolate mofetil, tacrolimus, everolimus, 6-mercaptopurine, infliximab, rituximab and several others. In this review we summarize the current standard of therapy but also efforts of providing novel therapeutic strategies to AIH patients.

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“…These findings were included in a subsequent review of the reported experiences with allopurinol in 13 patients with autoimmune hepatitis, and they strengthened the observations in the earlier report (Table 3). 212 The principal side effect was a reversible neuropathy that developed in two individuals (15%) 212,219 …”

Section: Investigational Opportunities To Improve Thiopurines As Secomentioning

confidence: 99%

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

Czaja

2020

Aliment Pharmacol Ther

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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.

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Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review

Cited by 16 publications

References 41 publications

Comparative efficacy and tolerability of treatments for adult autoimmune hepatitis: A systematic review and network meta‑analysis

Comparative efficacy and tolerability of treatments for adult autoimmune hepatitis: A systematic review and network meta‑analysis

Autoimmune Hepatitis: a Review of Established and Evolving Treatments

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

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