Efficacy of B Cell Depletion Therapy with Rituximab in Refractory Chronic Recurrent Uveitis Associated with Vogt-Koyanagi-Harada Disease

El‐Asrar, Ahmed M. Abu; Dheyab, Abdulsalam M; Khatib, D. El; Struyf, Sofie; Damme, Jo Van; Opdenakker, Ghislain

doi:10.1080/09273948.2020.1820531

Cited by 25 publications

(16 citation statements)

References 40 publications

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“…A total of 30.7% (27/88) patients received just 1 cycle of RTX, leading to disease remission for 81.5% (22/27), no observed response for 18.5% (5/27), and eventual disease recurrence in 54.5% of responders (12/22) at a mean of 8.0 months (range = 6.0 to 13.0 months; median = 7.0 months) despite continued treatment with other forms of systemic immunomodulatory therapies. In total, 69.3% (61/88) of treated patients received between two to 12 cycles of RTX at varying intervals: 4 weeks (20/58, 34.5%) [ 16 , 17 , 37 , 38 , 40 ], 8 weeks (3/58, 5.2%) [ 17 , 37 ], 3 to 6 months (1/58, 1.7%) [ 38 ], 6 months (25/58, 43.1%) [ 17 , 20 , 22 , 23 , 29 , 30 ] 8 months (1/58 1.7%) [ 25 ], 9 months (1/58, 1.7%) [ 25 ], 6 to 10 months (1/58, 1.7%) [ 24 ], or ≥ 12 months (4/58, 6.9%) [ 15 , 17 , 25 ]. Two studies employed increasing retreatment durations (2/58, 3.4%) [ 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…From 2005 to 2020, authors consistently used RTX as a third-line (90/95, 94.7%) medication to treat scleritis. While RTX was also used as predominantly a third-line medication (67/90, 74.4%) for treatment of refractory uveitis, some authors began to utilize RTX as a second-line (18/90, 20.0%) agent to treat VKH disease, npAIR, and CAR beginning in 2017 [ 14 , 29 ]. Of note, RTX was used as a first line-drug for three patients with npAIR and two with CAR [ 14 , 17 , 20 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Rituximab for non-infectious Uveitis and Scleritis

Cunningham

2021

J Ophthal Inflamm Infect

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Purpose To provide a comprehensive review of rituximab use for the treatment of non-infectious uveitis and scleritis. Methods Review of literature through December 2020. Results Individual data was available for 229 patients with refractory non-infectious uveitis (n = 108) or scleritis (n = 121) who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (uveitis: 67/90, 74.4%; scleritis: 90/96, 93.8%) at a mean of 33.5 months following the diagnosis of uveitis (range = 0 to 168.0 months; median = 24.0 months) and 39.4 months after diagnosis of scleritis (range = 1.0 to 168.0 months; median = 21.0 months). Patients with non-infectious uveitis and scleritis either received prior treatment with corticosteroids only (uveitis: 18/90, 20%; scleritis: 4/94, 4.3%), or with one (uveitis: 19/90, 21.1%; scleritis: 30/94, 31.9%), two (uveitis: 11/90, 12.2%; scleritis 27/94, 28.7%), or three or more (uveitis: 37/90, 41.1%; scleritis: 31/94, 33.0%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (uveitis: 45/87, 51.7%; scleritis: 87/114, 76.3%), followed by the Foster protocol (eight weekly infusions of 375 mg/m2 RTX; uveitis: 18/87, 20.7%; scleritis: 10/114, 8.8%), and the oncologic protocol (four weekly infusions of 375 mg/m2 RTX; uveitis: 5/87, 5.7%; scleritis: 6/114, 5.3%). Various other off-label regimens were used infrequently (uveitis: 19/87, 21.8%; scleritis 11/114, 9.6%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with non-infectious uveitis (81/97, 83.5%). Commonly treated uveitic diagnoses included non-paraneoplastic autoimmune retinopathy (30/107, 28.0%), juvenile idiopathic arthritis (21/107, 19.6%), Vogt-Koyanagi-Harada disease (12/107, 11.2%), and Behçet disease (11/107, 10.3%). Cases of non-infectious scleritis were most commonly attributed to granulomatosis with polyangiitis (75/121, 62.0%) and rheumatoid arthritis (15/121, 12.4%), and showed an even greater rate of positive therapeutic response (112/120, 93.3%) following RTX treatment. No side effects were reported in 76.3% (74/97) of uveitis and 85.5% (71/83) scleritis cases. Of those cases associated with RTX-induced adverse events, the most common were infusion reactions of various severity (11/35, 31.4%). Conclusions Overall, RTX appeared to be both effective and well-tolerated as second or third-line therapy for patients with non-infectious uveitis and scleritis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rituximab for non-infectious Uveitis and Scleritis

Cunningham

2021

J Ophthal Inflamm Infect

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“…With regard to non-infectious uveitis, rituximab has been shown to be effective in patients with chronic anterior uveitis (103), refractory Behcȩt disease-associated uveitis (104), JIA (105,106), VKH (11,107,108), multifocal choroiditis (109), and other more rare uveitides (110). The patients involved in these case reports or case series mainly developed severe uveitis with prolonged disease duration and resistance to topical and systemic corticosteroids, immunosuppressors, TNF-a inhibitors, or other biologics.…”

Section: B Cells Regulate T Cell Response Via Their Autoantibody-independent Functionmentioning

confidence: 99%

A Review of the Various Roles and Participation Levels of B-Cells in Non-Infectious Uveitis

Zhu

Chen

2021

Front. Immunol.

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Non-infectious uveitis is an inflammatory disorder of the eye that accounts for severe visual loss without evident infectious agents. While T cells are supposed to dominate the induction of inflammation in non-infectious uveitis, the role of B cells in the pathogenesis of this disease is obscure. Therefore, this review aimed to discuss diverse B-cell participation in different non-infectious uveitides and their roles in the pathogenesis of this disease as well as the mechanism of action of rituximab. Increasing evidence from experimental models and human non-infectious uveitis has suggested the participation of B cells in non-infectious uveitis. The participation levels vary in different uveitides. Furthermore, B cells play multiple roles in the pathogenic mechanisms. B cells produce autoantibodies, regulate T cell responses via antibody-independent functions, and constitute ectopic lymphoid structures. Regulatory B cells perform pivotal anti-inflammatory functions in non-infectious uveitis. Rituximab may work by depleting pro-inflammatory B cells and restoring the quantity and function of regulatory B cells in this disease. Identifying the levels of B-cell participation and the associated roles is beneficial for optimizing therapy. Diversified experimental model choices and emerging tools and/or methods are conducive for future studies on this topic.

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“…Biologics have been introduced in uveitis management, and guidelines recommend them upon systemic CS/IMT treatment failure ( Rosenbaum et al, 2019 ; Valenzuela et al, 2020b ). Studies have shown that the use of adalimumab [anti-tumor necrosis factor α (TNF-α) antibody] ( Couto et al, 2018 ; Hiyama et al, 2021 ) and rituximab (anti-CD20 antibody) ( Abu El-Asrar et al, 2020 ) improves visual acuity, alleviates inflammation, and allows for CS tapering. Case reports have shown favorable results for the use of infliximab (anti-TNF-α) ( Wang and Gaudio, 2008 ; Zmuda et al, 2013 ) and intravitreal bevacizumab (anti-VEGF-A) ( Wu et al, 2009 ; Park et al, 2011 ) as treatment of VKH.…”

Section: Vogt–koyanagi–harada Diseasementioning

confidence: 99%

miRNA Landscape in Pathogenesis and Treatment of Vogt–Koyanagi–Harada Disease

Vega-Tapia

Bustamante

Valenzuela

et al. 2021

Front. Cell Dev. Biol.

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miRNAs, one of the members of the noncoding RNA family, are regulators of gene expression in inflammatory and autoimmune diseases. Changes in miRNA pool expression have been associated with differentiation of CD4+ T cells toward an inflammatory phenotype and with loss of self-tolerance in autoimmune diseases. Vogt–Koyanagi–Harada (VKH) disease is a chronic multisystemic pathology, affecting the uvea, inner ear, central nervous system, and skin. Several lines of evidence support an autoimmune etiology for VKH, with loss of tolerance against retinal pigmented epithelium-related self-antigens. This deleterious reaction is characterized by exacerbated inflammation, due to an aberrant TH1 and TH17 polarization and secretion of their proinflammatory hallmark cytokines interleukin 6 (IL-6), IL-17, interferon γ, and tumor necrosis factor α, and an impaired CD4+ CD25high FoxP3+ regulatory T cell function. To restrain inflammation, VKH is pharmacologically treated with corticosteroids and immunosuppressive drugs as first and second line of therapy, respectively. Changes in the expression of miRNAs related to immunoregulatory pathways have been associated with VKH development, whereas some genetic variants of miRNAs have been found to be risk modifiers of VKH. Furthermore, the drugs commonly used in VKH treatment have great influence on miRNA expression, including those miRNAs associated to VKH disease. This relationship between response to therapy and miRNA regulation suggests that these small noncoding molecules might be therapeutic targets for the development of more effective and specific pharmacological therapy for VKH. In this review, we discuss the latest evidence regarding regulation and alteration of miRNA associated with VKH disease and its treatment.

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Efficacy of B Cell Depletion Therapy with Rituximab in Refractory Chronic Recurrent Uveitis Associated with Vogt-Koyanagi-Harada Disease

Cited by 25 publications

References 40 publications

Rituximab for non-infectious Uveitis and Scleritis

Rituximab for non-infectious Uveitis and Scleritis

A Review of the Various Roles and Participation Levels of B-Cells in Non-Infectious Uveitis

miRNA Landscape in Pathogenesis and Treatment of Vogt–Koyanagi–Harada Disease

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