Rituximab treatment experience in patients with complicated type 1 autoimmune hepatitis in Europe and North America

Than, Nwe Ni; Schmidt, David E.; Hodson, James; Wawman, Rebecca E.; Burak, Kelly W.; Botter, Meemee; Jones, Rebecca; Montaño-Loza, Aldo J.; Gautam, Nishant; Appanna, Gautham; Godkin, Andrew; Schramm, C; Lammert, Frank; Swain, Mark G.; Adams, Dawn; Hirschfield, Gideon; Oo, Ye Htun

doi:10.1016/s0168-8278(18)30652-4

Cited by 7 publications

(3 citation statements)

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“…Only recently, monoclonal antibodies, e.g., Rituximab and Infliximab, have effectively been used in patients with refractory or difficult to treat AIH [127, 128, 129] [130].…”

Section: Alternative and Second-line Treatmentmentioning

confidence: 99%

Autoimmune Hepatitis—Immunologically Triggered Liver Pathogenesis—Diagnostic and Therapeutic Strategies

Sucher

Gradistanac

et al. 2019

Journal of Immunology Research

107

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Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH is made clinically applying diagnostic scores; however, the heterotopic disease phenotype often makes a rapid determination of disease challenging. AIH responds favorably to steroids and pharmacologic immunosuppression, and liver transplantation is only necessary in cases with acute liver failure or end-stage liver cirrhosis. Recurrence or development of de novo AIH after transplantation is possible, and treatment is similar to standard AIH therapy. Current experimental investigations of T cell-mediated autoimmune pathways and analysis of changes within the intestinal microbiome might advance our knowledge on the pathogenesis of AIH and trigger a spark of hope for novel therapeutic strategies.

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“…Only recently, monoclonal antibodies, e.g., Rituximab and Infliximab, have effectively been used in patients with refractory or difficult to treat AIH [127, 128, 129] [130].…”

Section: Alternative and Second-line Treatmentmentioning

confidence: 99%

Autoimmune Hepatitis—Immunologically Triggered Liver Pathogenesis—Diagnostic and Therapeutic Strategies

Sucher

Gradistanac

et al. 2019

Journal of Immunology Research

107

View full text Add to dashboard Cite

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“…Another case series demonstrated biochemical improvement 3‐8 months later in two difficult‐to‐treat paediatric patients . The largest to date experience with rituximab assessed its effect retrospectively in 22 patients who failed second‐line therapy . Overall, improvement in transaminases, reduced need for steroids and lower relapse rate was noted at 24‐month follow‐up after administration of two doses of rituximab.…”

Section: Recent Data On Pharmacological Therapy Of Aihmentioning

confidence: 98%

Autoimmune hepatitis: Current and future therapeutic options

Doycheva

Watt

Gulamhusein

2019

Liver International

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Autoimmune hepatitis (AIH) is a rare immune‐mediated liver disease with few major advances in treatment options over the last several decades. Available options are effective in most patients albeit are imprecise in their mechanisms. Novel and more tolerable induction regimens and alternative options for management of patients intolerant or with suboptimal response to traditional therapies including in the post‐transplant setting remain an important unmet need. This review aims to summarize recent data on pharmacological options and investigational drugs in development for patients with AIH. Standard therapy using prednisone with or without azathioprine remains the mainstay of therapy and is effective in most patients. Budesonide may be considered for induction in early disease and in those with mild fibrosis, but has not been approved for maintenance therapy. Mycophenolate mofetil (MMF) in combination with steroids might be an alternative first‐line therapy, but results from a randomized trial are awaited. MMF as a second‐line maintenance agent has moderate efficacy though more frequent adverse events in patients with cirrhosis may be seen. Tacrolimus may be an equally effective second‐line option particularly in non‐responders, but data remain limited. Management of recurrent AIH post‐liver transplantation remains controversial with insufficient data to support long‐term steroid use. Moving forward, expanding the scope of therapeutic options to include biologics including B‐cell depleting agents may be a promising step. Recent insights in understanding the pathogenesis of AIH could serve as a basis for future therapies, including the elucidation of different immunoregulatory pathways and the potential role of the intestinal microbiome.

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“…Despite such little amount of published cases, RTX is extensively used as rescue therapy in clinical practice as showed by a recent real life survey among expert centers (97) and a multicentric study not yet published “in extenso” (98). The most dreaded infectious complication of RTX treatment, however, is a progressive, multifocal, and eventually lethal encephalitis caused by the Polyoma John Cunningham virus (JC), which may occur months or years after the beginning of the treatment (99).…”

Section: New Tools For Biological Therapymentioning

confidence: 99%

Novel Diagnostic and Therapeutic Strategies in Juvenile Autoimmune Hepatitis

2019

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Juvenile autoimmune hepatitis (JAIH) is a rare, chronic, inflammatory disease of the liver characterized by a complex interaction between genetic, immunological, and environmental factors leading to loss of immunotolerance to hepatic antigens. It affects both children and adolescents, most commonly females, and its clinical manifestations are quite variable. JAIH is progressive in nature and if left untreated may lead to cirrhosis and terminal liver failure. Although JAIH was first described almost 50 years ago, there have been few significant advances in the clinical management of these patients, both in terms of available diagnostic tools and therapeutic options. Aminotransferase activity, class G immunoglobulins and autoantibodies are the biomarkers used to diagnose AIH and monitor treatment response alongside clinical and histological findings. Despite their utility and cost-effectiveness, these biomarkers are neither an accurate expression of AIH pathogenic mechanism nor a precise measure of treatment response. Current standard of care is mainly based on the administration of steroids and azathioprine. This combination of drugs has been proven effective in inducing remission of disease in the majority of patients dramatically improving their survival; however, it not only fails to restore tolerance to hepatic autoantigens, but it also does not halt disease progression in some patients, it is often needed life-long and finally, it has deleterious side-effects. The ideal therapy should be enough selective to contrast immune-mediated live damage while preserving or potentiating the ability to develop permanent tolerance vs. pathogenic autoantigens. By reviewing the state of the art literature, this article highlights novel diagnostic and therapeutic strategies for managing pediatric AIH with a special focus on new strategies of immunotherapy. These promising tools could improve the diagnostic algorithm, more accurately predict disease prognosis, and provide targeted, individualized treatment.

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Rituximab treatment experience in patients with complicated type 1 autoimmune hepatitis in Europe and North America

Cited by 7 publications

References 0 publications

Autoimmune Hepatitis—Immunologically Triggered Liver Pathogenesis—Diagnostic and Therapeutic Strategies

Autoimmune Hepatitis—Immunologically Triggered Liver Pathogenesis—Diagnostic and Therapeutic Strategies

Autoimmune hepatitis: Current and future therapeutic options

Novel Diagnostic and Therapeutic Strategies in Juvenile Autoimmune Hepatitis

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