How to diagnose and treat NMOSD: Polish expert recommendations have emerged

NMOSD (neuromyelitis optica), formerly known as Devic's syndrome, is a rare, severe central nervous system disorder with an autoimmune background and aggressive course. NMOSD is characterized by pathological foci within the optic nerves, spinal cord and brain, leading to symptoms such as visual disturbances (up to and including total blindness), hemiparesis and/or severe pain in the extremities (affecting only the legs or both legs and arms), sensory disturbances, or sphincter disorders, among others. These symptoms do not have to occur at the same time, and the disease in most cases is projected. Each flare leaves a large neurological deficit, leading to disability and, in extreme cases, can even lead to death.

Diagnosing NMOSD

As experts point out, despite the diagnostic criteria defined in 2015, early and correct diagnosis of NMOSD can sometimes be difficult in clinical practice. Patients
with symptoms suggestive of NMOSD should be serologically tested for the presence of antibodies to aquaporin 4 (AQP4-IgG) in serum, preferably by cell-based assay (CBA), which is the most sensitive method. These antibodies are present in the majority of people with NMOSD (about 80% of patients), hence they are a specific diagnostic biomarker. In patients with confirmed presence of AQP4-IgG, i.e. the so-called seropositive patients, for the diagnosis of NMOSD it is sufficient to find clinical features of involvement of at least one of the following structures of the central nervous system: the optic nerve, spinal cord,area postrema, brainstem or intercerebrum, and to exclude other diseases that may give similar symptoms, primarily multiple sclerosis (e.g. by performing magnetic resonance imaging of the spinal cord before and after contrast agent administration, covering at least two sections of the spinal cord: cervical and thoracic).

Seronegative cases (that is, without the presence of NMOSD-specific antibodies to aquaporin 4 in the patient's blood serum) pose greater diagnostic problems. These cases require additional testing and a more detailed differential diagnosis,
in which diseases with a similar clinical picture (including other autoimmune diseases of the central nervous system, metabolic diseases and cancer) should be excluded.

Treatment of NMOSD

According to expert recommendations, the treatment of NMOSD consists of cast treatment and chronic immunosuppressive treatment aimed at preventing further casts. In the treatment of a flare, intravenous infusions of high doses of corticosteroids are recommended, and then steroid therapy should be continued orally with gradual dose reduction, depending on the severity of the flare. In the case of a particularly severe cast, the recommended treatment is to perform plasma exchange. In some cases, intravenous infusions of polyvalent immunoglobulins may also be considered.

Once NMOSD is diagnosed, it is necessary to start chronic treatment as early as possible to reduce the risk of a disease flare, since in NMOSD each flare is associated with a high risk of irreversible neurological deficits and patient disability. Both seropositive and seronegative NMOSD can be treated with non-selective immunosuppressive drugs and the monoclonal antibody rituximab. However, these drugs have no registered indication for use in NMOSD. In the treatment of seropositive NMOSD, three new molecules have appeared in recent years, showing very high efficacy in the treatment of this disease, and thus very significantly improving the prognosis of patients. These are monoclonal antibodies that can be used as first-line drugs in seropositive NMOSD patients:

• Eculizumab: administered intravenously as monotherapy
• inebilizumab: administered intravenously as monotherapy
• satralizumab: administered subcutaneously; can be used as monotherapy or as combination therapy
  with other immunosuppressive drugs.

These three drugs have different mechanisms of action on the immune system but all show high efficacy in preventing further relapses and thus increasing disability. Clinical studies show that as many as 80-90% of patients using these drugs do not experience relapses during their use. Currently in Poland, of the three monoclonal antibodies mentioned in the recommendations, only satralizumab is reimbursed. This treatment is available for patients with seropositive NMOSD under the B.138.FM drug program, i.e. for patients who are found to have pathogenic antibodies against AQP4 in their serum.

Source: Polish Neurological Review 2023; 19 (1): 24-37

https://journals.viamedica.pl/polski_przeglad_neurologiczny/article/view/PPN.a2023.0004

Commentary by Prof. Monika Adamczyk-Sowa, MD, president of the Multiple Sclerosis and Neuroimmunology Section of the Polish Neurological Society

The development and publication of up-to-date guidelines for the diagnosis and therapy of NMOSD was an urgent necessity, as completely new molecules have emerged in recent years that change the prognosis of patients. Until now, in NMOSD, we have not had the option of targeted, chronic immunomodulatory treatment and have used immunosuppressive or other off-label drugs in our patients with the disease. In 2019, with the European registrations of three drugs, there is an opportunity for effective immunomodulatory therapy for NMOSD with aquaporin 4 antibodies using monoclonal antibodies. These therapies can also be used as first-line drugs in these patients. As of November 1, 2023, there is a B.138.FM drug program for the treatment of patients with optic neuritis spectrum disorder, under which the drug satralizumab is available for patients. It is very important that NMOSD sufferers are correctly diagnosed and included in treatment under this drug program as soon as possible. This is especially important because NMOSD is a disease that leads very quickly to irreversible disability.

Commentary by Prof. Beata Zakrzewska-Pniewska, MD, chairman of the Coordinating Team for the treatment of patients with neuritis of the optic nerve and spinal cord (NMOSD).

Thanks to the favorable provisions, effective from November 2022, of the B.138.FM drug program, we have the opportunity to treat patients with NMOSD in accordance with the latest medical knowledge and current expert recommendations. The reimbursement program covers the modern drug used in NMOSD, namely satralizumab. According to the provisions of the drug program, patients who meet the following criteria together are eligible for satralizumab treatment:

- Age 12+;

- NMOSD diagnosis, based on current diagnostic criteria;

- The presence of antibodies to aquaporin 4 (anti-AQP4) in blood serum;

- The degree of disability, as assessed by the EDSS scale, ranging from 0 to 6.5 points inclusive;

- No contraindications to the use of this drug, as specified in the Summary of Product Characteristics;

- no prior treatment with another interleukin-6 inhibitor drug (this means excluding from the program patients with NMOSD previously treated with tocilizumab).

For patients who are of childbearing age, contraception is recommended). Patients who discontinue treatment with satralizumab under the drug program due to pregnancy may be re-admitted to it after the pregnancy ends. In patients qualified for the drug program, an evaluation of the efficacy and safety of treatment is carried out after 12 months of therapy, as is done in drug programs dedicated to patients with, for example, multiple sclerosis (MS), which have been running for many years.

Eligibility of patients for treatment with satralizumab in the drug program is carried out by the Coordinating Team for the Treatment of Patients with NMOSD Spectrum, based on the application prepared by the neurologist caring for the patient in question and sent to the Coordinating Team. More information on the rules of the Team can be found at the following link: https://uckwum.pl/dla-pacjenta/leczenie-nmosd/

Source: press mat.