Therapeutic options in neuromyelitis optica spectrum disorders

SUMMARY

Neuromyelitis optica is a relapsing inflammatory disorder of the central nervous system that manifests predominantly with attacks of optic neuritis and longitudinally extensive transverse myelitis; attacks are often severe. In contrast to multiple sclerosis, a secondary progressive phase is rare, and disability in neuromyelitis optica spectrum disorders is related to relapses. Thus, prompt and effective treatment of relapses, and early initiation of long-term immunosuppression to prevent subsequent attacks is required in order to prevent morbidity and mortality.

KEYWORDS:

• Neuromyelitis optica
• NMO
• NMOSD
• neuromyelitis optica spectrum disorders
• AQP4-Ab
• aquaporin-4
• treatment

Financial and competing interests disclosure

J Kitley was supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica and has received travel grants from Biogen Idec, Novartis and Teva and speaker honoraria from Novartis and Terumo BCT. J Palace is partly funded by highly specialized services to run a National congenital myasthenia service and a neuromyelitis optica service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Genzyme and MS Society. Her hospital trust receives funds for her role as clinical lead for the RSS and she has received grants from the MS society and Guthie Jackson Foundation for unrelated research studies. She is a board member for the charitable European MS foundation ‘The Charcot Foundation’ and on the steering committee for a European collaborative MS imaging group ‘MAGNIMS’. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Acute NMOSD relapses must be treated promptly with intravenous methylprednisolone ± plasma exchange.

• NMOSD with AQP4-Ab is a severe relapsing disease and patients should be started on long-term immunosuppression with azathioprine, mycophenolate or rituximab at first presentation.

• Azathioprine and mycophenolate take several months to exert maximum efficacy and NMOSD patients starting these agents should be kept on moderate dose prednisolone for the first 6 months of therapy to protect against early relapses.

• NMOSD with AQP4-Ab appears to be generally steroid dependent and many patients will require long-term low dose corticosteroids in addition to a steroid sparing agent to maintain remission.

• Long-term serological and clinical studies of NMO patients with AQP4-Ab are required to establish whether the disease ever ‘burns out’ over time and whether immunosuppression can ever be safely stopped.

• NMOSD without AQP4-Ab is often monophasic and patients presenting with a first attack do not need starting on long-term immunosuppression at first presentation.

• Management of relapsing NMOSD without AQP4-Ab is identical to management of NMOSD with AQP4-Ab.

• NMOSD with MOG-Ab has a risk of rebound relapses following the onset attack if corticosteroids are withdrawn too quickly and patients should be maintained on oral prednisolone for 6 to 12 months.

• Longer follow-up studies of MOG-Ab positive NMOSD patients are required to clarify the proportion who follow a relapsing course and to assess whether there are patient or disease-specific characteristics that can identify patients at risk of relapse who might benefit from immunosuppressant therapy at disease presentation.

• The pathogenesis of ‘true’ seronegative NMOSD needs studying to establish if therapies in development for NMOSD with AQP4-Ab are likely to also be helpful for this group of patients.