Page 17 - Read Online

Page 312 Ong et al. Neuroimmunol Neuroinflammation 2020;7:311-8 I http://dx.doi.org/10.20517/2347-8659.2020.05

Keywords: Neuromyelitis optica spectrum disorder, single-course rituximab, aggressive neuromyelitis optica
spectrum disorder

INTRODUCTION
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating
[1]
disorder of the central nervous system with preferential involvement of the optic nerve and spinal cord .
[2]
The disease has been reported worldwide with a prevalence ranging from 0.5-4.4/100,000 . In Malaysia,
the crude prevalence rate of NMOSD is 1.9 per 100,000 population with a crude annual incidence of 0.3 per
[3]
100,000 population . In this study, NMOSD patients notably experienced more relapses resulting in attack
related disability, had higher expanded disability status scale (EDSS) scores and longer disease duration
[3]
than MS patients . If untreated, 80% of NMOSD patients experience a second attack within 2 years and
the 5-year mortality rate can be as high as 68% with 50% of the surviving patients developing permanent
[4]
disability . The mainstay of treatment for NMOSD consists of immunosuppressant therapy. In the acute
management of relapses, corticosteroid and plasmapheresis are frequently used. However, long term use of
[5]
corticosteroid often leads to multiple side effects . Thus, conventional steroid-sparing immunosuppressive
agents such as azathioprine (AZA), methotrexate and mycophenolate mofetil (MMF) are widely utilised as
[4]
maintenance therapy to achieve remission and prevent relapses .
Recent evidence points to B cell-mediated humoral immunity in the pathogenesis of NMOSD. Rituximab
(RTX), a monoclonal antibody targeting the CD20 antigen on B cells, has been found to be effective in
several modest quality studies in terms of reducing relapse rates and improving patients’ outcomes [6-9] .
RTX offers the prospect of an alternative steroid-sparing regime in the treatment of NMOSD, particularly
[10]
when rapid disease control is required. Kim et al. demonstrated the benefits of induction RTX followed
by repeated doses to control disease activity when CD27 and memory B cells in the blood increased to
more than 0.05%. Nevertheless, treatment with RTX is expensive and can cause profound B cell depletion,
leading to the risk of severe immunosuppression and infection. Additionally, the monitoring of B cells and
CD27 or CD19 are costly and multiple courses of RTX are a burden in regions with limited resources. At
our institution, RTX is used as short course induction pulse therapy in patients with aggressive NMOSD
followed by de-escalation to steroid-sparing agents such as AZA or MMF. Recent studies also suggest
clustering of attacks occurring within 12 months of disease diagnoses, suggesting the hypothesis of “hitting
hard” with early therapy to dampen the early aggressive inflammatory activity and later, down regulating to
maintenance therapy may help in these fulminant situations .
[11]

METHODS
In each patient, a diagnosis of NMOSD was made based on criteria described by the International Panel
[1]
for Neuromyelitis optica (NMO) Diagnosis of 2015 . Relapses in this study were defined as objective
worsening or new neurological symptoms and signs lasting for at least 24 h. Aggressive NMOSD in our
cohort of patients was defined as one or more disabling relapses in the preceding 12 months in patients
with or without maintenance immunosuppressant therapy. Disabling relapses were defined as worsening
EDSS at the time of relapse to 6.5 or more, Medical Research Council power of 3/5 or worse in the lower
limbs, or visual acuity worse than 6/36 in one or both eyes at the time of relapse over the preceding one
year. The patients in our observational study were on stable doses of oral prednisolone for at least three to
six months prior to commencement of RTX.

This study was registered under the National Medical Research Register, Ministry of Health Malaysia
(NMRR-19-291-46157 S1).