Long-term Treatment
At present (since the year 2009 in the Czech Republic), it is possible to commence a long-term immunomodulating treatment of a patient as early as after the first clinical attack suspected of MS, if it was treated with corticoids.
This offers a great advantage because no time is lost by waiting for other attacks, with the patient losing a part of their CNS during this time of waiting. This knowledge was the result of studies with biological medicines carried out for populations of patients with a clinically isolated syndrome (CIS) (the first attack). These studies have shown that early treatment postpones another attack and leads to stabilisation of the disease in many patients.
Treatment in the Remission Stage of MS
After the first attack subsides, the patients often have a feeling that they are completely all right and do not need any therapy. Treatment is necessary for the very reason that this is the beginning of the disease and that it is important to prevent future deterioration. The situation is substantially more complicated with patients who have already been diagnosed with relapsing-remitting MS. Even though we know that most of them would benefit from the treatment, the rules for payment for such treatment limit the patients in various countries to such a degree that not all of them can be treated.
We can categorise the treatment into the first line treatment, which is safe but now always sufficiently effective, and the second line treatment (escalation treatment), which is provided if the first line treatment is ineffective and does not result in stabilisation of the patient. Possibly, it can also be used the first line treatment for patients who have poor prognostic signs: numerous severe relapses; their condition is not completely rectified after treatment of a relapse; a major finding was identified using MRI; relapses affecting the motor system and cerebellum.
1. First line treatment
2. Second line treatment
Treatment of Secondary Progression MS
In a situation, in which a large amount of nerve fibres in the CNS has already been lost and the patient’s status is a clinically stable, serious disability, the inflammation is unfortunately less tumultuous; it takes place as a smouldering inflammation at the periphery of the niduses and is essentially therapeutically inaccessible. The disability is irreversible and the medicines mentioned above has proved to be ineffective for progression of the disability when tried in this stage. If the patient is losing their ability to walk, we know that the medicines for the remitting stage have no effect.
It is not easy to explain to the patient that there is no point in continuing the treatment. Adverse reactions may prevail over the benefit. This fact must be communicated in a sensitive manner and must be accompanied with creating a plan for further care.
If the attending physician believes that it is still suitable to try to modify the inflammation, it is possible to use a pulse therapy using cytostatic drugs in combination with corticosteroids. It is meaningful to try out cyclophosphamide or mitoxantrone for a limited period of time and to monitor carefully whether it is beneficial to the patient. When cyclophosphamide is administered, it is necessary to attend to the urinary tract (sufficient hydration; sterile urine; cystoscopy once a year to exclude or detect possible urinary bladder carcinoma in time) and to monitor total blood count. Mitoxantrone is cardiotoxic; it is necessary to carry out a heart echo test before each infusion and to monitor the ejection fraction of the left chamber even several years after the end of the treatment. Total blood count is necessary. Both cytostatic drugs may induce early menopause and may damage spermatogenesis. When they are administrated, nausea commonly occurs and can be well controlled by setrons.
At present, there are still many patients in the Czech Republic who take small maintenance doses of oral corticosteroids in this stage of the disease. It is an “off-label” treatment; itis not supported by data of evidence-based medicine. However, it was derived from the treatment of other autoimmune diseases in the past; and at the times when there were no other medicines available, it gave at least some chance of modifying the inflammatory process. Regrettably, in the late stage of the disease, its use is not substantiated and it only brings about adverse reactions. However, with most patients, it is not possible to discontinue its administration and so its dose is reduced to the lowest possible dose and the adverse reactions, particularly the development of osteoporosis, are prophylactically treated.
Another medicine that we can encounter in this stage is azathioprine. Its efficacy for secondary progression MS has also not been proven. If a patient has been taking it for a long time (many years), it is necessary for the patient to stop taking it due to the possibility of development of bone marrow depression or tumour diseases. Things are similar with methotrexate.
Intravenous immunoglobulins were temporarily paid for by health insurance companies when they were indicated for remitting MS. At present, they are not paid for, and therefore their administration is being abandoned; moreover, data from clinical studies for their use are not sufficient. It has also not been proven that they prevent attacks after childbirth; timely resumption of the original treatment is recommended.
Oral corticosteroids, azathioprine, cyclophosphamide and intravenous immunoglobulins (and rituximab) are parts of the standard treatment regimen for neuromyelitis optica – a disease similar to MS.
Treatment of Primary Progression MS
There is no definite recommendation for this type of disease. There is less inflammation and there is more degeneration of the central nervous system. It is possible to try cytostatic drug pulse treatment like with the secondary progression. Fingolimod and ocrelizumab are in clinical trials.
Besides a well-designed symptomatic treatment, physiotherapy is definitely the crucial treatment regimen in the progressive stages of the disease.
Recommended literature: Havrdová E. et al., Roztroušená skleróza v praxi, Galén, Prague 2015.
Detailed information about drugs and their effects: www.sukl.eu.