Expert Panel Publishes Revised Consensus Recommendations for Diagnosis and Management of NMOSD

A multidisciplinary panel of experts has published a revised set of evidence-based recommendations for the diagnosis and management of neuromyelitis optica spectrum disorder (NMOSD) in Saudi Arabia, incorporating recent therapeutic developments and emerging biomarker insights since the 2022 consensus publication.^1,2 The updated guidance emphasized individualized care, antibody testing, long-term immunosuppressive strategies, and underscored the need for further research on treatment duration as well as failure criteria.

A group of neurologists, neuroimmunologists, epidemiologists, and pharmacists convened under the Saudi Neurology Society Multiple Sclerosis Chapter reviewed 56 studies through a GRADE assessment. From the initial 128 statements and 25 recommendations developed under various themes for voting, the process resulted in a final set of 27 recommendations and 90 statements. The finalized recommendations addressed key areas, including diagnostic strategies, diagnostic criteria, and acute and chronic treatments in NMOSD, as well as recommendations regarding the diagnosis and treatment of myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD).

"Over the past decade, neurologists—both locally and internationally—have become much more familiar with recognizing NMOSD and proactively testing for AQP4 antibodies. What these recommendations add is a stronger emphasis on using the correct testing methodology, especially in settings where access to live cell–based assays is limited," lead author Salman Aljarallah, MBBS, FRCPC, assistant professor of medicine at King Saud University in Saudi Arabia, told NeurologyLive^® in a recent interview.

"For MOGAD, the guideline highlights the need to be cautious with false positives, particularly when the antibody titers are low. This is something that continues to challenge us in daily practice, and the recommendations reinforce the importance of interpreting those results in the right clinical context," Aljarallah said. "The most important change in this guideline is the emphasis on starting biologic therapy as the first line and also supporting the earlier use of complement inhibitors when the concern of a potential severe outcome from a relapse."

Published in Multiple Sclerosis and Related Disorders, the guidance covered acute attack management, initial immunosuppressive therapies, treatment duration, and prognostic factors at diagnosis for potential failure of first-line treatments. The recommendations also discussed the use of rituximab, azathioprine (Imuran), mycophenolate mofetil (CellCept), and newer therapies, including ravulizumab (Ultomiris; Alexion), tocilizumab, inebilizumab (Uplizna; Amgen), satralizumab (Enspryng; Genentech), and eculizumab (Soliris; Alexion). Although newer therapies demonstrate promising efficacy, differences in safety, accessibility, and patient response highlight the need for further research to clarify their optimal role in treatment regimens.

"There was broad agreement that many NMOSD relapses are severe by nature, so the threshold for using high-efficacy biologics should be low. The panel stressed paying special attention to patients who already have significant baseline disability—for example, someone who has lost vision in 1 eye and depends entirely on the other. In those cases, the consensus was that treatment should be more aggressive from the start," Aljarallah added. "The major shift in this guideline is the clear support for using biologic therapy as first line, and for considering early complement inhibition when the clinical concern for a severe relapse is high."

Recommendations for Diagnosing and Managing NMOSD

Serology

• Serum AQP4-IgG testing using live cell-based assays (CBAs) is recommended as the first-line diagnostic test for patients with 1 or more core NMOSD clinical features.
• Testing is ideally performed during an active relapse and before starting immunosuppressive therapy to optimize detection.
• Repeat testing may be indicated in seronegative patients with strong clinical suspicion to improve diagnostic sensitivity.

MRI

• MRI findings should be interpreted cautiously in regions with high multiple sclerosis prevalence to reduce the risk of misclassification.
• MRI with gadolinium contrast may be used for additional evaluation in patients who are AQP4-IgG negative or when antibody testing is inconclusive or unavailable.

Diagnostic Criteria

• The 2015 International Panel for NMO Diagnosis criteria provide a framework integrating clinical, serological, and radiological data and are recommended for distinguishing NMOSD from other neurological disorders.

Treatment of NMOSD: Acute Attacks

Corticosteroids

• Intravenous methylprednisolone (1 g/day for 3-5 days) is recommended as first-line therapy for acute NMOSD relapses.

Plasmapheresis/Plasma Exchange (PLEX/TPE)

• PLEX may be considered for patients who do not respond to high-dose corticosteroids within 48 to 72 hours or for those with severe relapses.
• Therapeutic plasma exchange can be used for severe or refractory relapses.

Intravenous Immunoglobulin (IVIg)

• IVIg may be considered as an alternative when corticosteroids or PLEX are contraindicated, unavailable, or not feasible.

Relapse Prevention/Initial Immunotherapy

• Steroid-sparing immunosuppressive therapy is recommended for all patients.
• Rituximab is commonly used as a first-line therapy due to established efficacy and reduced steroid requirements.
• Mycophenolate mofetil and azathioprine may be considered for patients unable to tolerate rituximab.
• Azathioprine may also be used in seropositive patients with low disability or in seronegative patients without access to monoclonal antibodies.
• Complement inhibitors may be considered for patients with severe disease or a high risk of disability.
• Monoclonal antibodies, including eculizumab, ravulizumab, tocilizumab, and inebilizumab, may be considered for patients who cannot tolerate or do not respond to conventional immunosuppressive therapies.

IL-6 Pathway Inhibitors

• IL-6 receptor antibodies, such as tocilizumab and satralizumab, may be used for relapse prevention.
• Satralizumab is administered subcutaneously at weeks 0, 2, and 4, followed by every 4 weeks for patients with AQP4-positive disease.

Switching Treatment

• For AQP4-positive patients not responding to rituximab, alternative therapies may include complement inhibitors, IL-6 inhibitors, or anti-CD19 agents.

Treatment Duration

• Lifelong therapy is recommended for seropositive patients with relapsing disease.
• Gradual tapering may be considered for seronegative patients with stable disease; optimal timing requires further study.
• Decisions to discontinue therapy should consider relapse history, treatment-related toxicity, duration of therapy, and patient-specific factors.

MOGAD: Diagnosis

• Serum testing using live CBAs for full-length MOG-IgG is recommended, ideally at the time of the incident event; repeat testing at least 3 months later is suggested if the initial test is negative.
• Alternative diagnoses should be excluded to prevent misdiagnosis and avoid unnecessary testing.
• The International MOGAD criteria are recommended to guide diagnosis and management.
• MOG antibody testing is suggested in seronegative patients, particularly those with optic neuritis, myelitis, or atypical MRI features.

MOGAD: Management

• High-dose corticosteroids are recommended for acute relapses; long-term use should be minimized to reduce the risk of complications.
• IVIg and plasma exchange may be used for management of acute attacks.
• There is no consensus on treatment for newly diagnosed cases, but some evidence supports intervention in acute cases.
• Corticosteroids, cyclic IVIg, azathioprine, mycophenolate, or tocilizumab may be considered for patients at high risk of relapse.

“The newer biologic agents offer higher efficacy and a faster onset of action, but they also come with short- and long-term infection risks—especially since most NMOSD patients require prolonged, often lifelong, therapy. We still lack good predictors to help us individualize treatment duration or identify who might do well with a de-escalation approach," Aljarallah said. "I think we need large real-world data sets to understand patterns of relapse, durability of response, and what truly defines treatment failure. There is also growing interest in individualized dosing strategies. Biomarkers are emerging as a promising area in NMOSD, and they may eventually guide us toward more personalized treatment plans."

REFERENCES
1. Aljarallah S, AlThobaiti A, Abulaban A, et al. Consensus recommendations for the diagnosis and management of neuromyelitis optica spectrum disorder: a Saudi expert panel review. Mult Scler Relat Disord. Published online November 8, 2025. doi:10.1016/j.msard.2025.106847
2. Shosha E, Aljarallah SA, Al Fugham N, et al. Saudi consensus recommendations on the management of neuromyelitis optica spectrum disorders (NMOSD). Mult Scler Relat Disord. 2022;66:104062. doi:10.1016/j.msard.2022.104062