Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica

Yang, Chun-Sheng; Yang, Li; Li, Ting; Zhang, Da-Qi; Jin, Wei‐Na; Li, Minshu; Su, Ning; Zhangning, Nannan; Liu, Qiang; Shao, Zonghong; Yu, Chunshui; Shi, Fu‐Dong

doi:10.1212/wnl.0b013e3182a1aac7

Cited by 113 publications

(94 citation statements)

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“…As compared to previous studies our cohort included the higher number of patients and displayed a higher inflammatory activity. It may explain differences with reported disease efficacy (60-100 % of disease-free patients in cohorts with 5-30 NMO patients) [8][9][10]. A retrospective comparison between azathioprine, mycophenolate mofetil (MMF) and rituximab was made by Mealy et al in NMO patients who had similar ARR when first immunosuppression was considered, but some of these patients had received immunomodulating drugs or prednisone treatment before [11].…”

Section: Discussionmentioning

confidence: 99%

“…In spite of a large body of retrospective studies suggesting that immunosuppression may benefit NMO patients, no treatment is currently validated as efficient [1]. Azathioprine is the most widely used therapy worldwide but, in the last decade, some case series have reported the potential interest of mitoxantrone, mofetil mycophenolate, rituximab, and tocilizumab [2][3][4][5][6][7][8][9][10][11][12]. The presence of aquaporin 4 (AQP4) antibodies as a specific pathological marker of the disease led researchers to consider the role of B cells in NMO pathology [13].…”

Section: Introductionmentioning

confidence: 99%

“…The presence of aquaporin 4 (AQP4) antibodies as a specific pathological marker of the disease led researchers to consider the role of B cells in NMO pathology [13]. The potential effect of rituximab, an anti- Service de Neurologie, Hôpital Universitaire de la Timone, Marseille, France CD20 monoclonal antibody, remains discussed [4,5,[7][8][9][10][11] but, fortunately, randomized clinical trials with anti-CD20 and other biologics are ongoing (see clinicaltrial.org, NMO as key word). Although the odds of confirming the interest of anti-CD20 therapy in NMO with those RCT are high, the question of the optimal strategy will not be solved, especially the interest of rituximab use as first-line therapy, and the need for long-term maintenance.…”

Section: Introductionmentioning

confidence: 99%

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Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability

et al. 2015

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Neuromyelitis optica (NMO) is a life-threatening disease without any validated treatment strategy. Recent retrospective studies suggested the efficacy of B cell depletion without any distinction between first-line or rescue therapy. To assess whether rituximab as first-line therapy in NMO could efficiently control the occurrence of relapses. A retrospective analysis of NMO patients from NOMADMUS network found 32 patients receiving rituximab as first-line therapy. Main measures were number of relapse-free patients, changes in the annualized relapse rate (ARR), and changes in the EDSS. Tolerance was reported. At baseline, NMO patients were 45 ± 12.1 years old, with a sex ratio of 5.4, and 87.5 % of them had AQP4 antibodies. The median disease duration was 6.5 months (1-410), the mean EDSS was 5.8 ± 2.4 and the mean ARR was 3.8 ± 4.3. After rituximab with a mean follow-up of 28.7 ± 21 months, twenty-seven patients (84.3 %) were relapse free. Patients presented a 97 % decrease of ARR (p = 0.00001). EDSS decreased significantly to 3.9 ± 2.6 (p = 0.01). No relevant side effect was noted. New retrospective data are presented on RTX use in NMOSD. When used as first-line therapy RTX is highly effective and well tolerated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability

et al. 2015

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“…Since the use of azathioprine (AZA) with prednisone was first reported in 1998, 3 various immunosuppressants, including mycophenolate mofetil (MMF), 4,5 methotrexate, 6 rituximab, [7][8][9][10][11][12][13][14][15] and mitoxantrone hydrochloride, 16,17 have been introduced as therapeutic options for preventing relapse in patients with NMOSD. Azathioprine is a commonly used immunosuppressant for patients with NMOSD, in which treatment has resulted in a reduction of the annual relapse rate (ARR).…”

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confidence: 99%

Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

et al. 2014

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IMPORTANCE Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system. Recently, various immunosuppressant medications were introduced as therapeutic options for preventing relapse of NMOSD. However, our understanding of the effectiveness of mycophenolate mofetil (MMF) in treating patients with NMOSD is based on only a small number of studies.OBJECTIVE To evaluate the efficacy and safety of MMF treatment in patients with NMOSD. DESIGN, SETTING, AND PARTICIPANTSA 3-center retrospective review of our experiences, examining results from 59 patients with NMOSD (24 with neuromyelitis optica and 35 with a limited form of the disease) who were treated with MMF (1000-2000 mg/d). MAIN OUTCOMES AND MEASURESPatients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed. RESULTSOf the 59 patients, 1 with NMOSD who had to discontinue MMF use in the first month due to a rash was excluded. The remaining 58 patients were included in the drug-efficacy analysis. The median post-MMF annualized relapse rate was significantly lower than the pre-MMF annualized relapse rate (0.0 vs 1.5; P < .001). The Expanded Disability Status Scale scores also significantly decreased after MMF treatment (3.0 vs 2.5; P = .005). Thirty-five patients (60%) were relapse free, and Expanded Disability Status Scale scores were stabilized or improved in 53 patients (91%). Fourteen patients discontinued MMF treatment owing to ongoing relapse (10 patients), rash (1 patient), pregnancy (1 patient), and financial problems (2 patients), but MMF was generally well tolerated. CONCLUSIONS AND RELEVANCEIn this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.

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“…A genetic polymorphism in the fragment c gamma receptor 3A (FCGR3A) allele has been shown to be associated with insufficient memory B-cell depletion and an elevated risk of attacks during rituximab treatment [104]. It is controversial whether a reduction in the dose during long-term treatment or even lower initial doses of rituximab are sufficient to suppress disease activity [100,103,105,106]. Generally, optimal dosing of rituximab is important to lower the failure rate [79,103].…”

Section: Rituximab and Other B-cell-depleting Therapiesmentioning

confidence: 99%

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

Kleiter

Gold

2016

Neurotherapeutics

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Neuromyelitis optica spectrum disorders (NMOSD) are important evolving entities, which have reached much attention in the recent years. NMOSD are characterized by inflammatory lesions in the optic nerves, spinal cord, and central parts of the brain, as well as an autoimmune process directed against aquaporin-4. As disability in NMOSD accumulates by inflammatory damage from attacks, both the treatment and prevention of attacks are decisive for the long-term outcome. NMOSD attacks are treated with highdose intravenous corticosteroids and apheresis therapies, in particular therapeutic plasma exchange. In cases of incomplete remission, escalation of attack treatment is recommended. Preventive therapy is immunosuppressive and should by commenced as early as possible. Apart from classical immunosuppressants such as azathioprine and mycophenolate mofetil, repurposed biologicals are increasingly used. B-cell depletion with rituximab and other agents, inhibition of the interleukin-6 receptor with tocilizumab, and blockade of complement-mediated damage by eculizumab all are promising therapeutic strategies evaluated in randomized controlled trials. In this review, we will discuss present and future immunotherapies for NMOSD and also consider combination of treatments, plasma, cellular and other therapies. Current advances in immunopathological knowledge are translated into innovative concepts and begin a new era of NMOSD therapy.

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Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica

Cited by 113 publications

References 14 publications

Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability

Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability

Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

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