What's new in neuromyelitis optica spectrum disorder treatment?

Abstract

Optic neuritis, an optic nerve inflammatory disease presenting with acute unilateral or bilateral visual loss, is one of the core symptoms of neuromyelitis optica spectrum disorder (NMOSD). The diagnosis of NMOSD-related optic neuritis is challenging, and it is mainly based on clinical presentation, optical coherence tomography, magnetic resonance imaging scans, and the status of serum aquaporin-4 antibodies. In the pathogenesis, aquaporin-4 antibodies target astrocytes in the optic nerves, spinal cord and some specific regions of the brain eliciting a devastating autoimmune response. Current pharmacological interventions are directed against various steps within the immunological response, notably the terminal complement system, B-cells, and the pro-inflammatory cytokine Interleukin 6 (IL6). Conventional maintenance therapies were off-label uses of the unspecific immunosuppressants azathioprine and mycophenolate mofetil as well as the CD20 specific antibody rituximab and the IL6 receptor specific antibody tocilizumab. Recently, four phase III clinical trials demonstrated the safety and efficacy of the three novel biologics eculizumab, inebilizumab, and satralizumab. These monoclonal antibodies are directed against the complement system, CD19 B-cells and the IL6 receptor, respectively. All three have been approved for NMOSD in the US and several other countries worldwide and thus provide convincing treatment options.

Bilateral optic neuritis and encephalopathy as the atypical presentations of multiple sclerosis following severe acute respiratory syndrome coronavirus 2 infection

“…MOGAD and NMOSD are both more inclined than MS to exhibit longitudinal lesions that extend over 50% of the length of the optic nerve. [ 14 15 ] Our patient fulfills the 2017 revised McDonald criteria and presented with T1 hypointense lesions (black holes), which is still pertinent to making the diagnosis of MS. We suspect the immune reaction induced by COVID-19 infection could bring about the ADEM-like presentations in this patient.…”

The Coexisting Neuromyelitis Optica Spectrum Disorder and Systemic Lupus Erythematosus: A Therapeutic Challenge

“…Eculizumab, a humanised monoclonal antibody against C5 complement was approved by United States Federal Drug Agency (USFDA) for maintenance therapy of NMOSD. 22 Inebilizumab, another B cell depleting agent and satralizumab, an interleukin-6 (IL-6) inhibitor, have also been approved by USFDA for treating NMOSD in maintenance phase. 22 Eculizumab has rarely been reported to be beneficial in special circumstances in patients with SLE.…”

“… 22 Inebilizumab, another B cell depleting agent and satralizumab, an interleukin-6 (IL-6) inhibitor, have also been approved by USFDA for treating NMOSD in maintenance phase. 22 Eculizumab has rarely been reported to be beneficial in special circumstances in patients with SLE. 23 IL-6 inhibitors did not show any clinically meaningful response in trials.…”

Peripheral memory B cells in multiple sclerosis vs. double negative B cells in neuromyelitis optica spectrum disorder: disease driving B cell subsets during CNS inflammation

“…After receiving treatment with rituximab, the presence of regulatory B cells increases ( Quan et al, 2015 ). Satralizumab and tocilizumab both inhibit the IL6 receptor, disrupting lymphocyte activation ( Chu and Huang, 2022 ). Tocilizumab reduces memory B cells in the peripheral B cell subset, while regulatory B cells and plasmablasts remain unaffected ( Traub et al, 2020 ).…”