Anti‐TNFα Treatment in Children and Adolescents With Combined Inflammatory Bowel Disease and Autoimmune Liver Disease

Nedelkopoulou, Natalia; Vadamalayan, Babu; Vergani, Diego; Mieli‐Vergani, Giorgina

doi:10.1097/mpg.0000000000001759

Cited by 20 publications

(11 citation statements)

References 35 publications

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“…Another single-center retrospective analysis in 11 pediatric and adolescent patients with IBD and autoimmune liver disease included 2 patients with type 1 AIH and 9 with AIH-PSC overlap. (434) Infliximab (5 mg/kg) was infused to treat the IBD, and 3 patients were later treated with adalimumab after infliximab intolerance or failure. The IBD improved in most patients, and liver enzymes improved in 5.…”

Section: Very Lowmentioning

confidence: 99%

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

et al. 2020

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US children, 9%-12% (14-16) UK children, 38% (13) Age at presentation Peripubertal and adults Usually under 14 years (153) Mode of presentation Chronic symptoms common Acute onset (~40%) Ascites or GI bleeding rare Acute liver failure possible (555,556) Asymptomatic in 25%-34% Relapse frequent (108) Acute in 25%-75% Acute severe in 2%-6% Laboratory features Hypergammaglobulinemia IgA levels may be reduced (153) Autoantibodies ANA Anti-LKM1 SMA, anti-actin [Anti-LC1, Anti-LKM3] SLA Concurrent immune diseases Autoimmune thyroiditis Autoimmune thyroiditis Rheumatic diseases Diabetes mellitus IBD Vitiligo Autoimmune overlap with PSC (ASC in children) Common in children Rare Atypical pANCA-positive Atypical pANCA-negative Overlap with PBC Seen in adults (not children) Not reported Cirrhosis at presentation Adults, 28%-33% (especially elderly) Rare Children, ≤33% Remission after drug withdrawal Possible Rare, usually need long-term immunosuppression Abbreviations: GI, gastrointestinal; IgA, serum immunoglobulin A. *Removed from marketplace. Abbreviation: anti-PD-L1, antibody to programmed death protein ligand 1. taBle 6. Features of Drug-Induced aIH-like Injury and aIH Clinical Features Drug Induced AIH-Like Injury AIH Gender Mainly women (187) Female predominance, but men also affected (2,384,467) Acute onset Majority (>60%) (231) <20% (2,136) Hypersensitivity (fever, rash, eosinophilia) Up to 30% (231,232,613) Unusual (2,384,467) Temporal relationship with drug Positive (231-234) Negative (2,56,188) HLA DRB1*03:01 or DRB1*04:01 association None (236) Common (29) Concurrent autoimmune diseases Unusual (187) Present in 14%-44% (129,149-152) Cirrhosis at presentation Rare (187) 28%-33% (9,104-107) Management Stop offending drug ± glucocorticoids (187,231,232) Glucocorticoids with AZA (2,384,467) Relapse after drug withdrawal Rare (187) 60%-87% (243,244) Progression to cirrhosis Rare (187) 7%-40% (105) Survival without transplantation 90%-100% (187,232) 10-year survival, 89%-91% (105,451

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Section: Very Lowmentioning

confidence: 99%

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

et al. 2020

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“…Infliximab has been used as rescue therapy in patients with difficult‐to‐treat AIH; early experience demonstrated reduced inflammation; however, high rates of infectious complications were reported 112‐114 . However, a retrospective report of 11 paediatric cases with concomitant autoimmune liver disease (two with AIH and nine with autoimmune sclerosing cholangitis) treated with anti‐TNF therapy for severe inflammatory bowel disease demonstrated stable or improved liver function tests and only a single infective complication of asymptomatic cytomegalovirus viraemia 115 . There are concerns regarding idiosyncratic hepatotoxicity with anti‐TNF therapy and the impact of this on patients with already impaired liver function needs to be carefully considered.…”

Section: Novel Therapies Undergoing Clinical Assessment In Aihmentioning

confidence: 99%

Review article: experimental therapies in autoimmune hepatitis

Halliday

Dyson

Thorburn

et al. 2020

Aliment Pharmacol Ther

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Summary Background Current therapeutic options for autoimmune hepatitis (AIH) are limited by adverse events associated with corticosteroids and thiopurines and the limited evidence base for second‐ and third‐line treatment options. Furthermore, current treatment approaches require long‐term exposure of patients to pharmacological agents. There have been significant advances in the understanding of the mechanisms underpinning autoimmunity and an expansion in the available therapeutic agents for suppressing autoimmune responses or potentially restoring self‐tolerance. Aim To review the mechanisms and evidence for experimental therapies that are being actively explored in the management of AIH. Methods We have reviewed the literature relating to a range of novel therapeutic immunomodulatory treatment strategies and drugs. Results Drugs which block B cell‐activating factor of the tumour necrosis factor family (BAFF) and tumour necrosis factor α are currently in clinical trials for the treatment of AIH. Experimental therapies and technologies to increase immune tolerance, such as pre‐implantation factor and regulatory T cell therapies, are undergoing development for application in autoimmune disorders. There is also evidence for targeting inflammatory pathways to control other autoimmune conditions, such as blockade of IL1 and IL6 and Janus‐associated kinase (JAK) inhibitors. Conclusions With the range of tools available to clinicians and patients increasing, it is likely that the therapeutic landscape of AIH will change over the coming years and treatment approaches offering lower corticosteroid use and aiming to restore immune self‐tolerance should be sought.

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“…In 2 patients long-term infliximab treatment for 3-10 years permitted sustained remission without losing drug efficacy or causing infectious complications. Furthermore, Nedelkopoulou et al [133] reported improvement in liver function in 5 out of 8 children treated with infliximab for inflammatory bowel disease and concurrent AIH or AIH/PSC-overlap and no deterioration in the remaining 3. One study on etanercept in patients with both, rheumatic arthritis and AIH, reported biochemical and histological response in all 7 patients [134].…”

Section: Infliximabmentioning

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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Anti‐TNFα Treatment in Children and Adolescents With Combined Inflammatory Bowel Disease and Autoimmune Liver Disease

Abstract: IBD in patients with AILD can be aggressive, requiring escalation to anti-TNFα or switching to other biologics. In this series, anti-TNFα did not impair liver function and improved gut disease in most of the patients, indicating that it can be beneficial and safe.

Cited by 20 publications

References 35 publications

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

Review article: experimental therapies in autoimmune hepatitis

Autoimmune Hepatitis: a Review of Established and Evolving Treatments

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