Immune reconstitution therapy in NMOSD.

Importance: NMO spectrum disorders [NMOSD] is a relapsing autoimmune disorder with attacks of optic neuritis (ON) and transverse myelitis (TM). A large proportion of NMOSD patients have no or a partial recovery after relapse.

Observations: The neuro-immunological community now has a number of indicated agents for NMOSD therapy including eculizumab [Soliris®], inebilizumab (Uplizna®) and satralizumab (Enspryng®) with different mechanisms of action (MOA), rapidity of the onset of action (OOA) and issues of long-term safety. Autologous hematopoietic stem cell transplantation (AHSCT) may be another therapeutic option.

Conclusions And Relevance: The advantages of eculizumab are preservation of immunosurveillance, immediate onset of action and persistent efficacy but frequent IV administration and cost are important drawbacks. Inebilizumab allows a slight decrease in relapse free subjects over time but decreases B and plasmablast cell disease-inducing pathogenic antibody production. However, inebilizumab may cause immunosuppression. Satralizumab is immunomodulatory and self-administration but has delayed onset of action. AHSCT may be the best therapeutic option for the prevention and therefore the progression of NMO. In NMO, control the complement (eculizumab), reconstitute the immune system (AHSCT), transition to immunomodulation (satralizumab) and reserve immunosuppression (inebilizumab) as 4th line. AHSCT might also be used as rescue therapy for severe breakthrough disease after NMO-DMTs.