Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Kunchok, Amy; Malpas, Charles B; Nytrová, Petra; Havrdová, Eva; Alroughani, Raed; Terzı, Murat; Yamout, Bassem; Hor, Jyh Yung; Karabudak, Rana; Boz, Cavit; Özakbaş, Serkan; Olascoaga, Javier; Simó, Magdolna; Granella, Franco; Patti, Francesco; McCombe, Pamela A.; Csépány, Tünde; Singhal, Bhim; Bergamaschi, Roberto; Fragoso, Yára Dadalti; Al-Harbi, Talal; Türkoğlu, Recai; Lechner‐Scott, Jeannette; Lochard, Guy; Oreja‐Guevara, Celia; Pucci, Eugenio; Sola, Patrizia; Ferraro, Diana; Altıntaş, Ayşe; Soysal, Aysun; Vucic, Steve; Grand’Maison, François; Izquierdo, Guillermo; Eichau, Sara; Lugaresi, Alessandra; Onofrj, Marco; Trojano, María; Marriott, Mark; Butzkueven, Helmut; Kister, Ilya; Kalinčík, Tomáš

doi:10.1016/j.msard.2019.101868

Cited by 32 publications

(29 citation statements)

References 34 publications

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“…Also, this study showed that the risk of relapse decreased with prolonged disease duration. Kunchok et al found that the risk of relapse decreased with age [31]. Palace's study pointed that the risk of relapse decreased over time, especially when disease duration exceeded 10 years, and ARR decreased with disease duration even in patients who did not receive immunosuppressive therapy [15].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of azathioprine, mycophenolate mofetil, and rituximab in the treatment of neuromyelitis optica spectrum disorder and analysis of prognostic factors

et al. 2021

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ObjectiveThe study aims to compare the efficacies of the immunosuppressants most commonly prescribed for patients with neuromyelitis optica spectrum disorder (NMOSD). The predictors, which might be associated with relapse and disability in NMOSD, were also analyzed. Methods This retrospective study included NMOSD patients treated with azathioprine (AZA), mycophenolate mofetil (MMF), and rituximab (RTX). The annual relapse rate (ARR) and the incidence rates of adverse events were compared. Cox proportional-hazards model calculated the potential predictors of NMOSD relapse and disability. Results A total of 83 patients were included. The median treatment time of AZA group (n = 34), MMF group (n = 20), and RTX group (n = 29) were 19.5, 15.5, and 12 months, respectively. ARR of the three groups reduced significantly after treatment. In the three groups, 55.9%, 50%, and 79.3% of patients, respectively, were free from relapse. However, the difference among the three groups was of no statistical significance, possibly due to the small sample size. During the treatment, 32.4%, 15%, and 24.1% of patients experienced adverse events in the AZA group, MMF group, and RTX group, respectively. Additionally, the multivariate Cox analyses indicated that history of a severe attack and disease duration were associated with the risk of relapse after immunotherapy. Late-onset (≥ 50 years old) NMOSD patients were probably more susceptible to motor disability, and those with optic neuritis at onset were more likely to develop visual disability. Conclusions AZA, MMF, and low-dose RTX were all effective in reducing the relapse rate in NMOSD. The age at onset, disease duration, history of severe attacks, and primary syndromes might be significant prognostic predictors in NMOSD.

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Section: Discussionmentioning

confidence: 99%

Efficacy of azathioprine, mycophenolate mofetil, and rituximab in the treatment of neuromyelitis optica spectrum disorder and analysis of prognostic factors

et al. 2021

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“…Every relapse can leave patients with a disability, such as impaired vision, walk limitation, numbness. MMF has showed effectiveness and good tolerability in many previous studies, but there were still a considerable number of patients who did not respond well to the MMF (Kim et al, 2017;Poupart et al, 2020;Stellmann et al, 2017;Kunchok et al, 2020). Both clinical and genetic factors can affect individual response to MMF.…”

Section: Discussionmentioning

confidence: 99%

Effect of inosine monophosphate dehydrogenase-1 gene polymorphisms on mycophenolate mofetil effectiveness in neuromyelitis optica spectrum disorder patients

Liu

Luo

Liu

et al. 2021

Multiple Sclerosis and Related Disorders

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Background: Inosine monophosphate dehydrogenase-1 is the target of mycophenolate mofetil. This research investigated the association between the gene polymorphism of inosine monophosphate dehydrogenase-1 and effectiveness of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorder patients. Methods: Fifty-nine neuromyelitis optica spectrum disorder patients accepted Mycophenolate Mofetil therapy for 1 year at least were divided into two groups: relapsing (n=21) and non-relapsing (n=38). Four single-nucleotide polymorphisms (SNPs: rs2228075, rs2278294, rs2288550, and rs3793165) in the inosine monophosphate dehydrogenase-1 gene were detected. Then we analyzed the allelic frequencies and the genotypes of SNPs in two groups. Results: The allelic frequency of rs2278294 distributed differently between the relapse and non-relapsing patients (P=0.03), while no significant difference found in rs2228075, rs2288550 and rs3793165 between two groups.

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“…Older age was not affiliated with relapses or disability in one study, 46 but several others have shown a higher risk of disability with older age of disease onset. 33,45,47,48 Younger patients may present with slightly more severe NMOSD attacks, but they show improved rates of recovery (average 85% recovery at age 20) compared with older patients (60% recovery at age 60). 49 In contrast, patients with onset of NMOSD in childhood may have worse outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study from Brazil, reported greater disability in patients with onset of NMOSD before age 12 and death in 14% of patients who presented before age 21. 50 In addition to a higher risk of developing NMOSD, Asian and African ancestry may also have a higher likelihood of attacks 47,46,48 and higher rate of death 51 compared with other patients. Women with NMOSD have a higher percentage of pregnancy loss than expected for age.…”

Section: Discussionmentioning

confidence: 99%

“…Retrospecitve observational analyses have shown azathioprine to reduce relapse rate, and both azathioprine and mycophenolate mofetil to each slow disease progression as measured by EDSS. 48,71 A retrospective review of NMOSD patients treated with tacrolimus and prednislone found a reduction in annualized relapse rate after one year in both seropositive and seronegative patients. 72 A decrease in EDSS after two years was reported in treated seropositive NMOSD patients.…”

Section: Preventive Treatmentmentioning

confidence: 99%

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Update on neuromyelitis optica spectrum disorder

Holroyd

Manzano

Lévy

2020

Current Opinion in Ophthalmology

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Purpose of review.-Neuromyelitis optica spectrum disorder is an autoimmune disease that caused optic neuritis and transverse myelitis. Attacks can cause severe neurological damage leading the blindness and paralysis. Understanding of the immunopathogenesis of this disease has led to major breakthroughs in diagnosis and treatment. In the past 18 months, three successful phase 3 clinical trials have been published using targeted approaches to preventing relapses.Recent findings.-Updates in epidemiology, imaging, quality of life and treatment for acute relapse and prevention have been published in the past 18 months. Epidemiology studies are distinguishing patients based on their antigen specificity for aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG), which are increasingly recognized as separate immunological conditions. Imaging by MRI and optical coherence tomography continue to be developed as tools to distinguish NMOSD from other diseases. This is especially relevant as the recent clinical trials showed differences in response between AQP4 seropositive and seronegative patients. The three drugs that were tested for prevention of NMOSD relapses were eculizumab, inebilizumab and satralizumab. All of the trials were worldwide, placebo-controlled, doublemasked studies that demonstrated a clear benefit with each approach.Summary.-Recent research in NMOSD has resulted in improved diagnosis and approved treatments.

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Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Cited by 32 publications

References 34 publications

Efficacy of azathioprine, mycophenolate mofetil, and rituximab in the treatment of neuromyelitis optica spectrum disorder and analysis of prognostic factors

Efficacy of azathioprine, mycophenolate mofetil, and rituximab in the treatment of neuromyelitis optica spectrum disorder and analysis of prognostic factors

Effect of inosine monophosphate dehydrogenase-1 gene polymorphisms on mycophenolate mofetil effectiveness in neuromyelitis optica spectrum disorder patients

Update on neuromyelitis optica spectrum disorder

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