In the first post about Neuromyelitis Optica Spectrum Disorder (NMOSD), the significance of the Anti-Aquaporin 4 antibody (Anti-AQP4) was discussed. This antibody triggers very severe inflammation attacks in patients with NMOSD. In contrast to MS, however, NMOSD does not progress into a progressive disease stage in the later phases of the disease.In NMOSD, therefore, the disease attacks are the disease-causing element. The aim of successful therapy for NMOSD is therefore to prevent attacks safely. While this is also a significant goal of therapy for multiple sclerosis, given that the attacks of NMOSD often have a much more fatal course and recover incompletely, this goal must be pursued very consistently from the start.
Monoclonal Antibody Therapy for NMOSD
So if after a first attack there are indications of NMOSD, a different therapeutic approach must be taken than with MS. And the essential indication to take a different path consists, apart from typical changes in MRI, especially in the detection of the Anti-AQP4 antibody.
When the antibody was detected, the monoclonal antibody Rituximab was increasingly used in the past. Rituximab has also been used in the past to treat MS and targets B cells (i.e., the cell line from which antibody-producing cells also develop). However, Rituximab is not officially approved for use in NMOSD – so it is an “off-lable” therapy. However, Rituximab has proven to be highly effective in clinical practice for NMOSD and, despite its “off label” status, until recently was considered the most effective therapeutic agent for preventing NMOSD attacks. Especially after it was shown that some specific MS therapeutics like interferon-beta or natalizumab can rather worsen NMOSD.
In 2019 there was then a real breakthrough in the therapy of NMOSD. Three Phase III approval studies for the treatment of NMOSD with three different monoclonal antibodies were published at a high level. On the basis of this data, two of the three monoclonal antibodies have also recently been approved in the European Union. These are Eculizumab (Soliris®) and Satralizumab (Enspryng®). Inebelizumab, the third monoclonal antibody, has so far only been approved in the USA. However, approval by the European Medicines Agency is also to be expected.
Mechanism of action of therapies
Eculizumab (Soliris®) is an antibody directed against the complement system. Without its help, autoantibodies cannot unfold their fatal tissue-damaging effect. Therefore, only patients with NMOSD who could prove anti-AQP4 antibodies were included in the study. These are referred to as seropositive NMOSD patients. In this group, further NMOSD attacks could almost completely be prevented by using Eculizumab (during the study period). Satralizumab is an antibody against the cytokine IL6 (which is important for the maturation of antibody-producing cells). Both seropositive and seronegative patients were included in the approval study. Therefore, the overall study result was less impressive than that of Eculizumab. However, if you look at only the subgroup of seropositive patients – i.e. those with evidence of anti-AQP4 antibodies – a nearly similar positive picture emerges as with Eculizumab. Therefore, both new substances were officially approved only for the treatment of seropositive NMOSD.
For this group, two very potent substances are now available to prevent attacks. This is of course good news at first. It is a bit of a shame that these substances have not been tested against the previous gold standard Rituximab. This makes the relation of the effect to the previous therapeutic approach somewhat lacking. This is also unfavorable because the two new substances are many times more expensive than the “old antibody” Rituximab.
Nevertheless, this should not distract from the fact that a lot has really happened in the treatment of NMOSD in the last two years. This development is a real progress for this – albeit very rare disease. And perhaps the findings gained from this disease will also have positive effects on our understanding of aspects of multiple sclerosis. Because here too B cells and probably autoantibodies play a role.
Keep an eye on relapse treatment
Finally, a word about the treatment of an acute NMOSD disease attack. Here too, corticosteroids are primarily used. However, it has been shown that if there is no response, plasma exchange treatment (plasmapheresis) is a sensible option. This option should then be used quickly if the use of steroids shows no effect. And if superior efficacy is demonstrated compared to steroids, plasmapheresis should be used immediately and without delay in further attacks.
