Seeing a difference in neuromyelitis optica spectrum disorder: Integrating novel strategies into care

Learning objectives included:

• Outline strategies for diagnosing NMO early and accurately
• how new treatments target NMO relapse
• phase 3 study results
• new treatments impacting current algorithm

Kazuo Fujihara discussed early diagnosis as essential for reducing the burden of disease. He also shared how essential it is to understand the differences between MS and NMO, highlighting that the disease-modifying treatments for MS can exacerbate NMO.

• Specifically fingolimod, natalizumab, alemtuzumab and interferon-beta can all have a detrimental effect.
• Current treatments include high dose steroids, azathioprine, mycophenolate mofatil, rituxumab, methotrexate.
• Three new treatment choices have just passed their phase 3 trials specifically for NMO: eculizumab, inebilizumab and satralizumab.

Details of what constitutes a core clinical diagnosis for NMO were outlined.

Patient should be positive for cell-based aquaporin 4 (AQP4)-lgG as well as having clinical characteristics such as:

• Optic neuritis
• acute myelitis
• area postrema syndrome
• acute brainstem syndrome
• narcolepsy / acute diencephalic clinical syndrome
• symptomatic cerebral syndrome

The differential diagnosis between MS and NMO was discussed, with the following shared are more likely to indicate an NMO diagnosis:

• spinal cord lesions are localised to AQP4 high-expression sites
• bright spotty lesions are more common
• spinal cord atrophy and acute transverse myelitis is more severe
• brain atrophy is less severe
• Longitudinal extensive transverse myelitis (LETM) is very uncommon in MS

Atypical findings or red flags shared included sarcoidosis as it can mimic NMO, and short spinal cord lesions; whilst relatively uncommon in NMO, Kazuo noted a recent Mayo Clinic study found 15% of new diagnoses had shorter lesions.

Kazuo went into detail regarding AQP4's role in a healthy brain, and it's function in someone with NMO. He also highlighted some of the other biomarkers to be aware of, including:

• Th17-related cytokines
• CXCL1, CXCL5 and CXCL7 in the cerebrol spinal fluid
• Glial fibrillary acidic protein (GFAP) and Neurofilament light polypeptides (NfL)
• Exosomal microRNAs

Kazuo ended by highlighting that reduced quality of life was another marker of NMO, with most patients having had an initial diagnosis other than NMO. He noted findings from Beekman, 2019 that a delayed diagnosis often had a strong negative impact on people's physical function, and the many people experienced:

• increased pain,
• bladder and bowel problems
• sexual dysfunction
• an inability to work.

Sean Pittock looked at treatment goals for those with NMO, stating that the rapid progression of NMO requires aggressive immunosuppressive therapy. He also shared that:

• traditional approaches using immunosuppression (steroids and azathioprine) or B-cell targeted therapy (rituximab) have not been proven at a phase 3 trial,
• 40-80% of patients will relapse at last follow-up using these therapies.

He presented the findings of the latest phase 3 trials for eculizumab (PREVENT), inebilizumab (N-MOmentum) and satralizumab (SAKura-Sky and SAKura-Star), detailing their results, and any adverse effects.

(MS Academy faculty members Rachel Dorsey-Campbell and Dr Wallace Brownlee also had an interesting conversation on the PREVENT and SAKura-Sky studies following the EAN conference earlier this year, for further information.)

The three presenters then discussed the treatment options for a fictional case study, both at present, and in considering these new treatments, looking at preferences, lifestyle, accessibility to services, and more.