Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients

Radaelli, Marta; Moiola, Lucia; Sangalli, Francesca; Esposito, Federica; Barcella, Valeria; Ferré, Laura; Rodegher, Mariaemma; Colombo, Bruno; Fazio, Raffaella; Martinelli, Vittorio; Comı, Gıancarlo

doi:10.1177/1352458515594042

Cited by 75 publications

(51 citation statements)

References 33 publications

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“…Furthermore, Collongues et al recently described that in their cohort Body Mass Index was predictive of disability worsening on RTX, suggesting a possible impact of the dilution volume, and therefore of the effective dose, on response to RTX [22]. Few studies [10,17,[20][21][22][23][24] included patients treated with RTX-A and RTX-B, but no details of outcome measures are reported in relation to dosage regimens. Anyway, Kim et al reckon that once the disease is stabilized, less frequent RTX re-dosing might be sufficient to prevent relapses [17].…”

Section: Discussionmentioning

confidence: 99%

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Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study

et al. 2016

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Rituximab (RTX) efficacy in NMO is suggested by several case series. No consensus exists on optimal dosing strategies. At present the treatment schedules more frequently used are 375 mg/m2/week iv for 4 weeks (RTX-A) and 1000 mg iv twice, 2 weeks apart (RTX-B). Aim of this study is to confirm RTX efficacy and safety in the treatment of NMO and to evaluate whether a most favourable dosage regimen exists. Data on RTX-treated NMO patients were collected from 13 Italian Hospitals. 73 patients (64 F), were enlisted. RTX-A was administered in 42/73 patients, RTX-B in 31/73. Median follow-up was 27 months (range 7-106). Mean relapse rate in the previous year before RTX start was 2.2 ± 1.3 for RTX-A and 2.3 ± 1.2 for RTX-B. ARR in the first year of treatment was 0.8 ± 0.9 for RTX-A and 0.2 ± 0.4 for RTX-B, in the second year of treatment was 0.9 ± 1.5 for RTX-A and 0.4 ± 0.8 for RTX-B patients (p = 0.001 for the first year, ns (0.09) for the second year). RTX-B was more effective in delaying the occurrence of a relapse (HR 2.2 (95 % IC 1.08-4.53) p = 0.02). Adverse events were described in 19/73 patients (mainly urinary tract and respiratory infections, and infusion reactions). Two deaths were reported in severely disabled patients. Though with the limitations of an observational study, our data support RTX efficacy in NMO and suggest that high dose pulses might be more effective than a more fractioned dose.

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Section: Discussionmentioning

confidence: 99%

“…Some studies, ranging from 5 to 32 patients, have been produced demonstrating the effectiveness of RTX in NMO [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Recently, a cohort of 100 NMO-SD patients treated with RTX and with a long-term follow-up (median 67 months) was described [24].…”

Section: Introductionmentioning

confidence: 99%

Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study

et al. 2016

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“…In NMO, a recent string of studies show that the repopulation of peripheral blood by B cells, especially memory B cells, coincides with clinical relapses [51,[61][62][63]. Compared with healthy controls, patients with NMO have higher serum BAFF levels, which further increases after rituximab treatment [62].…”

Section: Ms and Nmomentioning

confidence: 99%

“…Open-label studies reported a significant reduction in relapse rate and subsequent stabilization or improvement in disability as measured by expanded disability status scale scores [63,[113][114][115][116][117]. Despite improving relapse rates and reducing disease activity reduced AQP4-IgG titers are not consistently associated with clinical improvement, even after long-term B-cell depletion [118].…”

Section: Inflammatory Myopathiesmentioning

confidence: 99%

“…However, these results were based on a very small number of patients. Close monitoring of CD19+ B-cell depletion and reconstitution thereafter could provide a tool for relapse prevention and timely treatment, while further improving the benefit-risk ratio of treatment [63]. B-cell repopulation after B-cell depletion with rituximab in patients with NMO was characterized by the predominance of Bregs and restored the pretreatment disturbed balance between regulatory and memory B cells back to an advantageous state [51].…”

Section: Biomarkers Of Clinical Response To B-cell-depletion Therapiesmentioning

confidence: 99%

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Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

2016

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B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antibody-producing cells and, most importantly, as sensors, coordinators, and regulators of the immune response. B cells, among other functions, regulate the T-cell activation process through their participation in antigen presentation and production of cytokines. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules or Bcell trophic factors bestows a rational approach for treating autoimmune neurological disorders, even when T cells are the main effector cells. This review summarizes basic aspects of B-cell biology, discusses the role(s) of B cells in neurological autoimmunity, and presents anti-B-cell drugs that are either currently on the market or are expected to be available in the near future for treating neurological autoimmune disorders.

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Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders

Damato¹,

Evoli²,

2016

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IMPORTANCE Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies characterized by predominant involvement of the optic nerves and spinal cord. In most patients, an IgG autoantibody binding to astrocytic aquaporin 4, the principal water channel of the central nervous system, is detected. Rituximab, a chimeric monoclonal antibody specific for the CD20 B-lymphocyte surface antigen, has been increasingly adopted as a first-line off-label treatment for patients with NMOSDs. OBJECTIVE To perform a systematic review and a meta-analysis of the efficacy and safety of rituximab use in NMOSDs, considering the potential predictive factors related to patient response to rituximab in this disease. EVIDENCE REVIEW English-language studies published between January 1, 2000, and July 31, 2015, were searched in the MEDLINE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov databases. Patient characteristics, outcome measures, treatment regimens, and recorded adverse effects were extracted.FINDINGS Forty-six studies were included in the systematic review. Twenty-five studies that included 2 or more patients with NMOSDs treated with rituximab were included in the meta-analysis. Differences in the annualized relapse rate ratio and Expanded Disability Status Scale score before and after rituximab therapy were the main efficacy measures. Safety outcomes included the proportion of deaths, withdrawals because of toxic effects, and adverse effects. RESULTS Among 46 studies involving 438 patients (381 female and 56 male [sex was not specified in 1 patient]; mean age at the outset of treatment, 32 years [age range, 2-77 years]), rituximab therapy resulted in a mean (SE) 0.79 (0.15) (95% CI, −1.08 to −0.49) reduction in the mean annualized relapse rate ratio and a mean (SE) 0.64 (0.27) (95% CI, −1.18 to −0.10) reduction in the mean Expanded Disability Status Scale score. A significant correlation was observed between disease duration and the Expanded Disability Status Scale score. Adverse effects were recorded in 114 of 438 (26%) patients treated with rituximab. Specifically, 45 patients (10.3%) experienced infusion-related adverse effects, 40 patients (9.1%) had an infection, 20 patients (4.6%) developed persistent leukopenia, 2 patients (0.5%) were diagnosed as having posterior reversible encephalopathy, and 7 patients (1.6%) died. CONCLUSIONS AND RELEVANCEThis systematic review and meta-analysis provides evidence that rituximab therapy reduces the frequency of NMOSD relapses and neurological disability in patients with NMOSDs. However, the safety profile suggests caution in prescribing rituximab as a first-line therapy.

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Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients

Cited by 75 publications

References 33 publications

Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study

Rituximab in the treatment of Neuromyelitis optica: a multicentre Italian observational study

Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders

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