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Page 316 Ong et al. Neuroimmunol Neuroinflammation 2020;7:311-8 I http://dx.doi.org/10.20517/2347-8659.2020.05

there have been several studies assessing the effectiveness of monoclonal antibody therapy, targeting CD20
epitope of the B cell lineage that is important in the pathogenesis of the disease [8,9,13,15-17] . In these studies,
there was reduction in annualized relapse rates and improvement in disability as measured by the EDSS.

However, in our resource limited setting, RTX is expensive and obtaining the medication for our patients
remains a huge challenge. Thus, we had to use a dosing schedule of lower frequency and a single course of
RTX was applied followed by oral immunosuppression to treat these patients. Data collected retrospectively,
showed a significant reduction in the frequency of relapses, ARR in NMOSD patients with aggressive
disease especially in those failing conventional immunomodulators. Remission was also maintained in 75%
[5]
of patients for 4 years. Similar to the study conducted by Bedi et al. , we avoided abrupt withdrawal of oral
prednisolone to prevent early relapses in those patients. Other immunomodulators were switched off while
RTX was given. All our patients were on stable doses of oral prednisolone and they were either tapered
off or reduced to the lowest possible maintenance dose of 5 to 20 mg after subsequent doses of RTX were
given, or when reasonable doses of conventional steroid-sparing agents was on board for an appropriate
time limit without further disease relapse. Such an approach may have a positive effect on relapse control
and contributed to the stability of disease activity after single dose RTX therapy.

To date, there has been no standard guideline or consensus on RTX treatment for patients with NMOSD.
Existing protocols used to induce and maintain remission are characterized by heterogeneity in terms of
infusion and monitoring schedules and methods. Previous studies practiced either prescheduled RTX
induction regimen every 6 months, or retreatment based on B cell depletion monitoring [6-8,16-18] . CD19,
CD20 and CD27 are among the commonly used treatment-related biomarkers [13,14,16,17] . However, our center
lacks the facilities to monitor treatment with these tests though we are aware of the need to objectively test
this for treatment response. We utilized lymphocyte enumeration tests by flow cytometry to estimate the
B cell population as a guide to treatment. Nevertheless, the test is expensive and was only done in 50% of
our patients who underwent RTX therapy. Thus, the data was too scarce to make a definite conclusion on
retreatment decisions. Therefore, retreatment was guided mainly by the severity and frequency of ongoing
attacks. In addition, our data demonstrated that eighty seven percent of our patients showed improvement
in EDSS score and none of them required retreatment with RTX.

In resource-limited hospitals, a single induction course of RTX treatment may be a therapeutic and
economic option to suppress disease activity. We recognized that oral prednisolone during RTX treatment
may potentially confound the analysis, however the overlapping benefit of steroids with RTX may be
crucial to avoid sudden withdrawal of immunosuppressants that can potentially cause an early relapse. The
doses of steroids were kept stable during this period and other immunosuppressants were withdrawn to
prevent possible adverse events.

Several studies have shown the benefits of low dose RTX in terms of improvement in ARR, disability scores
[17]
and time to next relapse [17,19,20] . Kim et al. reported a less frequent RTX retreatment approach which could
maintain remission in a subset of NMOSD patients. It is postulated that the initial high induction dose
of RTX (IV 1000 mg × 2 doses given 2 weeks apart) may be adequate to prevent early B cell repopulation,
which is seen in some studies with lower initial doses of RTX [14,15] . To our knowledge, there has been no
study to address the efficacy of a single course of RTX therapy followed by oral immunosuppressants
maintenance in the management of aggressive NMOSD. In our small cohort of patients, regardless of the
initial number of relapses and EDSS scores, majority responded very well to this treatment strategy and
remained relapse-free.

[21]
Unlike the meta-analysis published by Damato et al. , which recorded 26% of patients treated with RTX
[21]
had adverse reactions, none of our patients exhibited any side effects. Specifically, Damato et al. reported