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

Zephir, Hélène; Bernard‐Valnet, Raphaël; Lebrun, C.; Outteryck, Olivier; Audoin, Bertrand; Bourre, Bertrand; Pittion, Sophie; Wiertlewski, Sandrine; Ouallet, J.-C.; Neau, Jean‐Philippe; Ciron, Jonathan; Clavelou, Pierre; Marignier, Romain; Brassat, David

doi:10.1007/s00415-015-7852-y

Cited by 88 publications

(70 citation statements)

References 20 publications

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“…This chronic astrocytopathy preferentially targets the optic nerves and spinal cord, resulting in severe and potentially devastating sequelae such as paralysis and blindness. Despite the life-threatening consequences of uncontrolled disease activity, there are no validated treatment strategies for NMOSD [1–3]. …”

Section: Introductionmentioning

confidence: 99%

Use of rituximab and risk of re-hospitalization for children with neuromyelitis optica spectrum disorder

Gmuca

Xiao

Weiss

et al. 2018

Mult Scler Demyelinating Disord

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Background Treatment algorithms for neuromyelitis optica spectrum disorder (NMOSD) vary, and sparse data exist regarding the impact of initial treatments on disease course. We aimed to determine whether administration of rituximab during first hospitalization reduces 1-year readmission rates. Methods We conducted a retrospective cohort study of subjects with NMOSD using the Pediatric Health Information System database from 2005-2015. Subjects were ages 1 to 21 years who received glucocorticoids and an ICD-9-CM code indicating neuromyelitis optica (NMO) during first hospitalization. All subjects had at least 12 months of continuous enrollment. The primary exposure was ≥1 rituximab dose during first hospitalization. We tested for the association of rituximab use with all-cause re-hospitalization, the primary outcome, using survival analysis. Re-hospitalization was considered if a hospital admission occurred > 30 days after initial discharge with exclusion of admissions with re-dosing of rituximab and data were censored at 12 months. Secondary outcomes included time to and median duration of re-hospitalization using 25th percentiles of survival time and the Wilcoxon-rank sum test, respectively. Results Of 180 subjects who met inclusion criteria, 71.7% were female and the median age was 13 years (IQR: 10, 15). 52 subjects (28.9%) received rituximab during first hospitalization, and there was an increasing trend in rituximab use over time (p<0.01). Overall, 36.7% of children were readmitted and time to readmission was a median of 365 days (IQR: 138, 365). Rituximab exposure was not associated with re-hospitalization (adjusted HR: 0.71: 95% CI: 0.38, 1.34) nor a reduced time to re-hospitalization. Median duration of re-hospitalization was 2 days shorter in the rituximab exposed group (p=0.02). Receipt of physical therapy, a surrogate marker for neurologic impairment, during first hospitalization was associated with re-admission within 12 months (adjusted HR: 4.81; 95% CI: 1.14, 20.29). Conclusions Among children with NMOSD, first-line administration of rituximab was not associated with risk of or time to re-hospitalization. Rituximab use was found to be associated with a shorter duration of re-hospitalization. Need for physical therapy during first hospitalization was independently associated with an increased risk of re-admission.

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Section: Introductionmentioning

confidence: 99%

Use of rituximab and risk of re-hospitalization for children with neuromyelitis optica spectrum disorder

Gmuca

Xiao

Weiss

et al. 2018

Mult Scler Demyelinating Disord

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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: 91%

“…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: 98%

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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“…In a 2015 retrospective study, Zephir et al explored the use of rituximab as first line therapy in 32 patients with NMOSD. 27/32 patients were relapse-free at follow-up; reductions in annualised relapse rate and improvements in disability were observed suggesting rituximab as first line treatment is both effective and well tolerated 12. The early initiation of rituximab may be of paramount importance in preventing relapses and permanent disability in antibody positive NMOSD cases.…”

Section: Discussionmentioning

confidence: 96%

Neuromyelitis optica spectrum disorder presenting as rhomboencephalitis

2018

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Rhomboencephalitis, at least in its acute phase, is often a severely disabling syndrome, and can be life threatening. A range of underlying conditions can lead to this clinical syndrome. Rapid diagnosis to initiate treatment early is key to a beneficial outcome. We report the case of a 22 year old Afro-Caribbean woman, who presented with a two -week history of walking difficulties, upper limb incoordination and slurred speech. Her brainstem function deteriorated at pace, and she developed hypersomnia. A broad diagnostic approach led to prophylactic treatment for the most common infectious causes. This did not improve her symptoms. Non-infectious inflammatory causes were therefore considered and plasma exchange treatment was initiated leading to marked improvement within days. Screening for autoimmune conditions confirmed aquaporin-4 positive neuromyelitis optica spectrum disorder (NMOSD) as the underlying cause. Immunotherapy with rituximab was started. So far, no relapse has been observed. While the definition of NMOSD continues to be refined, aquaporin-4 testing should be considered early in patients presenting with rhomboencephalitis who do not respond to antibiotic and antiviral treatment. Vigilance and early intervention are key to limit morbidity and mortality from NMOSD.

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

Cited by 88 publications

References 20 publications

Use of rituximab and risk of re-hospitalization for children with neuromyelitis optica spectrum disorder

Use of rituximab and risk of re-hospitalization for children with neuromyelitis optica spectrum disorder

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

Neuromyelitis optica spectrum disorder presenting as rhomboencephalitis

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