The therapeutic landscape for multiple sclerosis is now broad. Nevertheless, the goal of neuroprotective and remyelinating therapy has not yet been achieved. The aim of the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) was therefore to promote and improve research and learning among professionals. The basis this year was the translation of basal immunology to applied therapy.
The trend is toward earlier and more aggressive treatment of multiple sclerosis (MS). This is one of the main pieces of information that has been circulated and also stated in the revised guideline. Depending on the disease characteristics and those of the patient, more potent drugs should be considered. Also new is the recommendation for siponimod in secondary progressive MS with evidence of inflammatory activity in the disease. In addition, more detailed information was provided on the use of disease-modifying therapies during pregnancy and lactation and for women with high disease activity who wish to become pregnant.
A brief overview of the most important innovations:
- The full range of disease-modifying medications should be prescribed by a neurologist who has expertise in MS and access to adequate infrastructure to ensure proper monitoring of patents, comprehensive evaluation, early detection of side effects, and the ability to treat these side effects promptly.
- Early selection of a more effective disease-modifying drug should be considered depending on disease activity.
- Patients with clinically isolated syndrome (CIS) strongly suggestive of MS and abnormal MRI with lesions suggestive of MS but not meeting criteria for MS should be offered interferon or glatiramer acetate.
- The choice of appropriate medication in patients with relapsing-remitting MS depends on disability progression, disease severity (clinical or radiographic activity), patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.
- In patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), treatment with siponimod or other therapies used in relapsing-remitting MS should be considered.
- Although evidence is limited, treatment with siponimod or anti-CD20 monoclonal antibodies should be considered in patients with secondary progressive MS without evidence of inflammatory activity in whom progression has recently begun.
- For patients with primary progressive MS, ocrelizumab should be considered, especially in early stage and active (clinically and/or radiologically) disease.
- Women of childbearing age should be advised that disease-modifying MS therapies are not approved during pregnancy, with the exception of interferons and glatiramer acetate.
- For women with highly active disease who wish to become pregnant, there are a number of treatment options:
- Treatment with long-lasting effects such as alemtuzumab or cladribine, provided that at least four and six months, respectively, have elapsed between the last dose and conception
- Treatment with anti-CD20 drugs before pregnancy, with advice to wait two to six months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy; or
- In patients treated with natalizumab, continue treatment during pregnancy with a 6-week extended dosing regimen until the end of the second trimester or until 34 weeks gestation. Week and resumption of treatment after delivery (in neonates exposed to natalizumab, watch for hematologic abnormalities and liver function).
- During breastfeeding, only interferons and ofatumumab are currently approved.
Biomaker NfL mirror
In recent years, serum NfL levels have been found to reflect ongoing inflammatory neuroaxonal injury. Therefore, it was considered to use it as a prognostic marker for disease activity, disability progression and response to treatment. For this purpose, 309 MS patients and 59 healthy control subjects were analyzed in a study. Their serum NfL concentrations were classified as high (>8 pg/ml) or normal (<8 pg/ml). The primary endpoint was disease progression after two years. The researchers defined disease progression as three or more new cerebral MRI lesions, confirmed Expanded Disability Status Scale (EDSS) progression, or new clinical relapse. Cross-sectional analysis confirmed previous observations that high serum NfL levels are associated with increased clinical disability, higher numbers of T2 lesions and new T2 lesions, high T2 lesion volume, and retinal axonal loss. The researchers also found that patients with high serum NfL levels at baseline had a 2.6-fold increased risk of disease progression after two years. The results suggest that NfL in serum may be a sensitive biomarker for progressive neuroaxonal degeneration.
Reduce sleep disorders with the help of melatonin
Sleep problems are common in people with MS, but unfortunately are often neglected. Undiagnosed obstructive sleep apnea was detected in 65% of those affected. However, to date, the relationship between MS and sleep disorders has not been adequately studied. Therefore, a double-blind, placebo-controlled crossover study addressed this issue. Participants had a Pittsburgh Sleep Quality Index (PSQI) of ≥5 or an Insomnia Severity Index (ISI) of greater than 14. Patient-reported scores for sleep disturbance, sleep quality, daytime sleepiness, fatigue, ambulation, and mood were also recorded. Half of the participants were treated with melatonin administration for the first two weeks and then switched to placebo. For the other half, the opposite procedures were followed. Results demonstrate that melatonin improved average sleep duration (6.96 vs. 6.67 hours). In addition, trends toward statistical significance were evident in the ISI, the PSQI component 1, and the NeuroQoL fatigue score. Work suggests that the decline in melatonin secretion in MS may be due to a progressive failure of the pineal gland in the pathogenesis of MS. This would explain the positive effect of melatonin administration. However, further, larger studies are needed to provide conclusive findings.
Long-term prognosis with Barcelona risk score
In patients with clinically isolated syndrome, long-term prognosis can be predicted early in treatment based on a combination of clinical, biological, and imaging data. The Barcelona risk score is based on sex, age at CIS, CIS topography, number of T2 lesions, and presence of infratentorial and spinal cord lesions, contrast-enhanced lesions, and oligoclonal bands.
Patients were then divided into low, intermediate, and high risk groups. The three groups had different outcomes on MRI scans, clinical factors, and quality of life over the course of their disease. The high-risk group had the shortest time to reach an EDSS of 3.0 and also had a higher likelihood of progression on MRI examinations and quality-of-life measures. The results are a confirmation that this classification is really meaningful at the beginning of the disease.
InFo NEUROLOGY & PSYCHIATRY 2021; 19(6): 30-31 (published 1/12/21, ahead of print).
