Neuromyelitis optica (NMOSD) - Treatment

At present there is no cure for NMOSD so management focuses on the following key areas:

1. Treating acute attacks/relapses
   2. Preventing relapses
   3. Treating the residual symptoms of the relapse

Relapses/Attacks
A high dose steroid, Methylprednisolone is usually given during a relapse. Steroids work by dampening the immune system and reducing inflammation around the site of nerve damage. They are given:

• Intravenously (through a vein) 1g daily for 5-7 days or
• Orally (taken by mouth) 500mg-2g daily for 5-7 days,
• In combination of intravenous and oral, followed by
• A tapering course of oral steroids over several months.

If steroids don’t help, what next? When attacks progress or do not respond to corticosteroid treatment, Plasma Exchange is most frequently used or sometimes Intravenous Immunoglobulins may be given.

Plasma Exchange (PLEX)

This is a technique in which the blood is drawn out of the body and the plasma (which contains the antibodies) is separated. The blood is then returned back into the body with fresh plasma. However this will only remove the antibody from the blood – the white cells that make the antibody (B cells) are still present in the blood. There is some evidence from controlled clinical trials that this helps patients with NMOSD.

Immunoglobulins (Ig)

Immunoglobulins are a blood product made from pooled plasma from many different people. Its mode of action is not completely understood, but it does block harmful antibodies and other immunological factors. Immunoglobulin is given through an intravenous infusion at a rate, dose and time which is individualised for each patient. Possible side effects can occur with IVIg. These are usually mild such as headache and high blood

Preventing relapses

In NMOSD disabilities are accumulated from each acute attack including visual problems and/or paralysis of limbs. So it makes sense to try and prevent relapses. Immunotherapies are powerful medicines that dampen down the activity of the body’s immune system. Drugs such as Prednisolone, Azathioprine, Methotrexate or Mycophenolate are used to allow reduction of steroids. All these treatments increase the risk of serious infections therefore blood will be monitored for full blood count, kidney and liver function.

Drugs commonly used in NMO
Oral Prednisolone tablets: Steroids are good immunosuppressants. After a diagnosis of NMO, oral steroids are used until other treatments are in place (Azathioprine for example can take 3-6 months to get to an effective level). In many patients relapses may occur even on gradual reduction of the steroids and they may need to continue on a low dose of steroids for longer periods. Often a maintenance dose is required.
Long-term treatment side effects including; weight gain, acne, indigestion, cataracts, osteoporosis (thinning of the bones), deterioration of the head of the thigh bone and diabetes. To reduce the side effects of Prednisolone other medication is taken such as an antacid Omeprazole or Lansoprazole, tablets for bone protection Alendronic acid and calcium supplements.

Azathioprine (also known as Immuran), Methotrexate and Mycophenolate (cellcept) have similar efficacy when it comes to suppressing the immune system. They all have side effects that are well understood, but need to be explained to you before you take the medication.

A certain percentage of patients will either not tolerate or relapse whilst on the above medications. If this happens, your doctor will consider a different medication to try and prevent relapses.

Other treatments available

These medications are considered to be “2nd line” treatments (i.e. used after trying the above medications). As with most medications, the more effective they are, the higher the risk of side effects. This is always a consideration when offering you medications.

Rituximab

This is an intravenous medication, treatment commences with 2 infusions 2 weeks apart. After this we monitor your bloods monthly to see when the next infusion is required. subsequent infusions are single dose so you only need to attend once. Retreatment varies from person to person but is usually around 6-9 month between. Rituximab is from a family of drugs called “monoclonal antibodies” which are capable of depleting B-cells that are responsible for producing NMOSD antibodies. A version is of Rituximab called Truxima is being used widely in UK.

IVIg
Immunoglobulins are a blood product made from pooled plasma from many different people. Its mode of action is not completely understood, but it does block harmful antibodies and other immunological factors. Immunoglobulin is given through an intravenous infusion at a rate, dose and time which is individualised for each patient.

Plasma Exchange (PLEX)
This treatment aims to remove the harmful antibodies from the blood. Using a specialised technique, the blood is drawn out of the body and the plasma is separated. The blood and plasma are then returned back into the body without these antibodies. The process is very much like dialysis but removes antibodies instead of waste.

Cyclophosphamide

This is another well-established chemotherapy that suppresses the immune system. There is very little evidence for its use in NMOSD.

Other treatments in NMOSD

Eculizumab is being used in a small number of patients where relapses are occurring whilst they are on Rituximab infusions. It is a humanized monoclonal antibody. The exact mechanism for its efficacy in NMOSD is unknown, but is believed to be related to inhibition of the formation of the membrane attack complex mediated by C5b.

Tocilizumab, like Eculizumab, is being used in a small number of patients where relapses are occurring whilst they are on Rituximab infusions. It is also a monoclonal antibody which targets Interleukin-6 receptor and binds to them effectively blocking their role in the immune inflammatory response.

Satralizumab is a humanized investigational recycling anti-IL-6 receptor monoclonal antibody currently in state III of trials for treating NMOSD.

Research

Due to the rarity of NMOSD currently there is little research available. Hence the importance for the two national centres to recruit as many of the NMOSD population into different trials as possible. This will gain further understanding towards future treatment and management of NMOSD

Please contact the following for further information:

• Dr Saif Huda, Consultant Neurologist, The Walton Centre, Liverpool, 0151 556 3532
• Professor Jackie Palace, Consultant Neurologist, John Radcliffe Hospital Oxford, 01865 231905
• Professor Angela Vincent, Consultant Immunologist at John Radcliffe Hospital, Oxford

Some of the current research

Audits

• UK Rituximab usage in NMOSD. Not yet completed. This is an audit examining the efficacy and safety of rituximab therapy in the UK NMOSD cohort
• Prednisolone and bisphosphonate usage in Liverpool NMOSD cohort
• Data collection regarding CD 19/27 results in relapsing rituximab patients
• Causes of death in AQP4-IgG NMOSD (Neuromyelitis Optica Spectrum Disorder)

Clinical trials

• Phase 1b study of ABX-1431 in patients with NMOSD and related disorders (ABIDE Therapeutics). ABX-1431 is new, potential therapy for chronic central neuropathic pain. It is an oral medication that modulates the endocannabinoid neurotransmitter system. Oxford and Liverpool are the two centres for this trial. Trial closed and results pending.
• Phase 3 double blind trial to evaluate the safety and efficacy of eculizumab in relapsing NMO patients (PREVENT Study, Alexion Pharmaceuticals). Eculizumab is a terminal complement inhibitor. This is an international trial. Dr Jacob at The Walton Centre is the lead investigator in the UK and we have three patients enrolled in the study in the UK. The trial has closed and results were strongly positive

Other research projects

• Treatment of MOG-IgG-associated demyelination with Rituximab. A multinational retrospective study. Initial results presented at AAN Annual Meeting in Los Angeles, April 2018. Lead investigator: Dan Whittam
• A multicentre retrospective review of MRI in patients with MOG-IgG-associated demyelination. Presented at ABN Annual Meeting in Birmingham, May 2018. Lead investigator: Dr Saif Huda
• Comparison of fixed high dose with variable low dose rituximab in neuromyelitis optica spectrum disorder. Presented at ABN Annual meeting in Edinburgh, May 2019. Lead investigators: Tricia Kelly and Dan Whittam
• A clinical proteomics study to understand the immune tolerance mechanisms in patients with MOG-Ab demyelinating disease. Lead investigator: Dr Saif Huda
• Advanced MRI study to understand the structure and function of the brain in patients with NMOSD. Lead investigator: Amal Alorainy
• International approaches to treatment of MOG IgG. Lead investigator: Dan Whittam
• Study to investigate T-cell mediated immunity, the effects of treatment and the role of the gut in causing NMOSD. Lead investigator: Hari Krishna
• A prospective study to investigate the burden of infections in patients with NMOSD. Lead investigators: Tricia Kelly and Dan Whittam
• A retrospective study to investigate clustering of autoimmune diseases in patients with NMOSD. Lead investigator: Sam Linaker
• A retrospective study of patients with paraneoplastic NMOSD. Lead investigators: Ali Daashti, Saif Huda and Venkatraman Karthikeayan.
• Systematic review of treatment in MOG-Ab demyelination. Lead investigator: Anu Jacob
• International Study of OCT in MOG-IgG demyelination. Lead investigator: Venkatraman Karthikeayan
• Review of treatment outcome with IVIG in patients with MOG-Ab. Lead investigator: Saif Huda
• International study of pregnancy outcomes in MOG-IgG. Lead investigators: Saif Huda and Sam Linaker
• A cross-sectional study to examine the effect of employment, driving and relationships on quality of life in NMOSD. Lead investigator: Kerry Mutch

Future research

Over the last few years research has increased worldwide, particularly assessing immunology, radiology, causes and possible future treatments for NMOSD. However as the condition is so rare, it is difficult to organise clinical trials (and hence the need to identify as many people with NMOSD as possible).

Please speak to your local NMOSD team to get the most up-to-date information on trials and research.

What about stem cells?

Currently, research into stem cell treatment is only in its initial stages. Some researchers are hopeful that stem cell treatments may be helpful for people with NMOSD in the future.