Aquaporin-4 antibody titration in NMO patients treated with rituximab

Valentino, Paola; Marnetto, Fabiana; Granieri, Letizia; Capobianco, Marco; Bertolotto, Antonio

doi:10.1212/nxi.0000000000000317

Cited by 60 publications

(31 citation statements)

References 36 publications

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“…For 84/188 samples (from 7 patients), data on anti-AQP4 IgG titers were available as well. 23 In addition, in the present study, 37 samples were evaluated for anti-AQP4 IgG titer (median sampling time interval = 4.5 months, range 3.0–7.0 months). In the remaining 48/236 samples (median sampling time interval = 13.5 months, range 7–25 months), anti-TET, anti-VZV, and anti-EBNA IgGs were tested.…”

Section: Methodsmentioning

confidence: 99%

Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders

Marcinnó

Marnetto

Valentino

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo evaluate the long-term effects of rituximab (RTX) on total and specific immunoglobulins (Igs) in patients with neuromyelitis optica spectrum disorders (NMOSDs).MethodsTotal IgG, IgA, and IgM levels were evaluated in 15 patients with NMOSDs treated with RTX (median follow-up 70 months). Anti-aquaporin 4 (AQP4)-IgG titration was performed on samples from 9 positive patients. Anti-tetanus (TET), anti-varicella-zoster virus (VZV), and anti-Epstein–Barr virus nuclear antigen (EBNA) IgGs were also tested in patients with NMOSDs and in 6 healthy controls (HCs).ResultsRTX reduced total IgG by 0.42 g/L per year, IgA by 0.08 g/L per year, and IgM by 0.07 g/L per year. Hypogammaglobulinemia (hypo-IgG) (IgG < 7 g/L) developed in 11/15 patients. Severe hypo-IgG (IgG < 4 g/L) was found in 3/15 patients, of whom 2 patients developed serious infectious complications. In group analysis, anti-AQP4 IgG titers were reduced by RTX over time, and a significant correlation between anti-AQP4 IgG titers and total IgG levels was found. The effects of RTX were observed on pathogen-specific IgGs as well. In particular, the levels of anti-TET IgG in patients were significantly lower than those in HCs. The half-life of anti-TET IgG was reduced by about 50% in patients compared with the general population.ConclusionsLong-term RTX treatment is associated with the risk of hypo-Ig and reduction of anti-TET protection in patients with NMOSDs. Results obtained in this study suggest the importance of monitoring total and specific Ig levels before and during treatment with anti-CD20 drugs to prevent hypo-Ig–related complications and to optimize clinical management.

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Section: Methodsmentioning

confidence: 99%

Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders

Marcinnó

Marnetto

Valentino

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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“…A similar low incidence of 3% has been reported in MS patients by Salzer et al [11], but the drop in the aggregate serum IgG levels was slight. Significant hypogammaglobulinemia with associated infections has rarely been reported in patients with MS or neuromyelitis optica treated with rituximab and mostly as single case reports [22,23]. It is of note that in the large series of RA patients reported by Vollenhoven et al [17], the incidence of serious infections was similar before and after development of hypogammaglobulinemia suggesting that these patients might have an inherent high risk of developing serious infections, possibly related to their underlying disease or concomitant/ previous therapies.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of rituximab in multiple sclerosis: A retrospective observational study

Zeineddine¹

2017

Preprint

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Objective. To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. Methods. Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. Results. A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6-12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p < 0 0001) and from 0.25 to 0.16 in PMS patients (p = 0 593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusionrelated reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. Conclusion. In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.

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“…The discovery and investigation of aquaporin-4 (AQP4)-antibodies [21,[31][32][33][34][35] have revolutionized NMOSD diagnostics by setting the disease apart from MS [36,37] and substantially changing NMOSD treatment [38] which considerably differs from classic diseasemodifying treatment in MS [39][40][41][42][43][44][45][46][47][48]. However, especially against the background of emerging evidence on myelin oligodendrocyte glycoprotein (MOG) -antibody-positive cases related to NMOSD, the heterogeneous pathophysiology of NMOSD still needs to be fully elucidated [49][50][51][52][53][54][55][56][57][58].…”

Section: Nmosd Visual Pathway White Matter Damage Patternsmentioning

confidence: 99%

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

et al. 2017

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The afferent visual pathway represents the most frequently affected white matter pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt brain tissue damage and quantify pathological processes. DTI facilitates the reconstruction of major white matter fiber tracts allowing for the assessment of structure-function and damage-dysfunction relationships. In this review, we outline DTI studies investigating the afferent visual pathway in idiopathic optic neuritis (ON), NMOSD, and MS. Since MS damage patterns are believed to depend on multiple factors, i.e., ON (anterior visual pathway damage), inflammatory lesions (posterior visual pathway damage), and global diffuse inflammatory and neurodegenerative processes, comprehensive knowledge on different contributing factors using DTI in vivo may advance our understanding of MS disease pathology. Combination of DTI measures and visual outcome parameters yields the potential to improve routine clinical diagnostic procedures and may further the accuracy of individual prognosis with regard to visual function and personalized disease outcome. However, due to the inherent limitations of DTI acquisition and post-processing techniques and the so far heterogeneous and equivocal data of previous studies, evaluation of the true potential of DTI as a possible biomarker for afferent visual pathway dysfunction is still substantially limited. Further research efforts with larger longitudinal studies and standardized DTI acquisition and post-processing validation criteria are needed to overcome current DTI limitations. DTI evaluation at different levels of the visual pathway has the potential to provide markers for individual damage evaluation in the future. As an imaging biomarker, DTI may support individual outcome prediction during personalized treatment algorithms in MS and other neuroinflammatory diseases, hereby leveraging the concept of predictive, preventive, and personalized medicine in the field of clinical neuroimmunology.

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Aquaporin-4 antibody titration in NMO patients treated with rituximab

Cited by 60 publications

References 36 publications

Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders

Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders

Safety and efficacy of rituximab in multiple sclerosis: A retrospective observational study

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

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