Comparative Analysis of Disease-modifying Treatments for Double Seronegative Neuromyelitis Optica Spectrum Disorder
Joao Vitor Mahler1, Gerome Vallejos2, Takahisa Mikami2, Philippe-Antoine Bilodeau2, Guilherme Silva3, Samira Apostolos-Pereira3, Bruna Leles1, Giovanna Manzano2, Emily Gibbons4, Ekdanai Uawitha5, Manisha Ramprasad6, Ahmetcan Sezen7, Olivia Pasquale8, Angie Kim9, Raveena Vij9, Feng Gai10, Yanjun Guo10, Ilya Kister11, Ayse Altintas12, Hesham Abboud13, Sasitorn Siritho5, Anu Jacob14, Saif Huda4, Dagoberto Callegaro3, Marcelo Matiello2, Michael Levy2
1Neurology, Division of Neuroimmunology & Neuroinfectious Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 2Division of Neuroimmunology & Neuroinfectious Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 3Departamento de Neurologia, Hospital das Clínicas da Faculdade de Medicina da USP, 4Walton Centre NHS Foundation Trust, 5Siriraj  Neuroimmunology Center, Siriraj Hospital, Mahidol University, Thailand, 6Case Western Reserve University School of Medicine, Cleveland, Ohio, 7Koç University, 8Creighton University School of Medicine, 9NYU Grossman School of Medicine, 10Dept of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China, 11NYU School of Medicine, 12Koc University School of Medicine, 13Multiple Sclerosis and Neuroimmunology Program, University Hospitals Cleveland Medical Center, 14Cleveland Clinic Abu Dhabi
Objective:
To determine the comparative effectiveness of different disease-modifying treatments (DMTs) in preventing relapses in patients with double seronegative neuromyelitis optica spectrum disorder (DS-NMOSD) that fulfill IPND-2015 criteria.
Background:

DS-NMOSD is characterized by demyelinating attacks that resemble those in seropositive patients, but display persistent negative serum anti-AQP4 and anti-MOG cell-based assays. These patients currently lack FDA-approved DMTs. Moreover, data that explores their response to distinct DMTs is largely observational and pre-dates the publication of MOGAD diagnostic criteria.


Design/Methods:

Deidentified data was collected retrospectively from electronic health records at each study site, using REDCap, from inception until July 2024. Appropriate institutional board review approval was obtained at each institution.


Inclusion criteria

  1. Diagnosis of NMOSD according to the IPND-2015 diagnostic criteria in the absence of anti-AQP4 antibodies (2 core clinical syndromes and at least one supporting MRI-criteria)

  2. At least one negative serum CBA for anti-MOG and anti-AQP4

Exclusion criteria

  1. No DMT received

Results:

Thirty-six patients were included. 69% were female, 61% were Caucasians, and 58% were Latino/Hispanics. The mean age at onset was 31 (SD 19.7), and the mean disease duration was 8.8 (SD 6.9) years. Twenty-seven patients (75%) experienced a relapsing course. The most common clinical presentations at onset were transverse myelitis (61%) and optic neuritis (56%). Simultaneous transverse myelitis and optic neuritis at onset occurred in 7 patients (19%).

Survival analysis revealed different time-to-relapse Kaplan-Meier curves when comparing treatment periods covered by a non-specific immunosuppressant versus when covered by a B-cell depleting agent, however, univariate Cox-Proportional-Hazards comparison yielded a non-significant p-value based on the a priori definition of significance (HR 2.26, 95CI 0.90-5.69, p=0.074).


Conclusions:

Our study constructed a well-characterized cohort of double-seronegative IPND-2015 fulfilling NMOSD patients. Survival analysis revealed a potential for better relapse prevention with the use of anti-CD20 drugs in this population, however, sample size likely limited quantitative analysis.

10.1212/WNL.0000000000209081
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