BACKGROUND: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance. OBJECTIVES: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate). DESIGN: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD. METHODS: This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW). RESULTS: After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070-0.092) for natalizumab patients and 0.191 (0.178-0.205) for BRACETD patients (p < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42-0.65); p < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients. CONCLUSION: Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.

• Klíčová slova
• multiple sclerosis, natalizumab, real-world evidence,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Natalizumab is an effective therapy in the treatment of relapsing-remitting multiple sclerosis; it induces lymphocytosis (NIL, natalizumab-induced lymphocytosis) and changes the peripheral lymphocyte pattern. METHODS: This study aims to evaluate NIL, peripheral blood lymphocyte subsets, CD4/CD8 ratio, and their impacts on JCV index and clinical data-No Evidence of Disease Activity (NEDA-3) and annualized relapse rate (ARR) in patients treated with natalizumab. RESULTS: Forty-one patients (33 women) were included in the study. The mean duration of follow-up on natalizumab treatment was 6.7 ± 3.2 years. Significant increases in relative lymphocytosis after 1 month, with a median of 40.4% (- 34.1 to + 145.5%) (p < 0.001), and after 1 year (49.0% (- 9.3 to + 127.6%)) (p < 0.001) were found. Significant differences were found after 1 month when comparing NIL between patients JCV-seroconverting (20.6% (- 17.7 to 72.7%)) and stable JCV-seronegative ones (43.5% (- 6.3 to +96.3%)) (p = 0.04). No significant difference NIL level was found between the patients exhibiting NEDA-3 status and those without it. ARR on natalizumab treatment correlated with CD4/CD8 ratio (r = 0.356; p = 0.021); patients who maintained NEDA-3 status over the whole treatment period exhibited a lower CD4/CD8 ratio (1.89 ± 1.08 vs. 2.5 ± 0.73; p < 0.04). CONCLUSION: This contribution reports the CD4/CD8 ratio as a possible biomarker for better clinical efficacy of natalizumab in patients exhibiting a lower CD4/CD8 ratio. NIL did not correlate with long-term therapeutic efficacy in patients treated with natalizumab, but was demonstrated as lower in patients JCV-seroconverting in the course of follow-up.

• Klíčová slova
• Flow cytometry, JC virus, Multiple sclerosis, Natalizumab, T lymphocytes,
• MeSH
• CD8-pozitivní T-lymfocyty MeSH
• imunologické faktory škodlivé účinky   MeSH
• lidé MeSH
• lymfocytóza * chemicky indukované   MeSH
• natalizumab škodlivé účinky   MeSH
• progresivní multifokální leukoencefalopatie * MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * MeSH
• virus JC * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunologické faktory MeSH
• natalizumab MeSH

Neurology is one of the typical disciplines where personalized medicine has been recently becoming an important part of clinical practice. In this article, the brief overview and a number of examples of the use of biomarkers and personalized medicine in neurology are described. The various issues in neurology are described in relation to the personalized medicine and diagnostic, prognostic as well as predictive blood and cerebrospinal fluid biomarkers. Such neurological domains discussed in this work are neuro-oncology and primary brain tumors glioblastoma and oligodendroglioma, cerebrovascular diseases focusing on stroke, neurodegenerative disorders especially Alzheimer's and Parkinson's diseases and demyelinating diseases such as multiple sclerosis. Actual state of the art and future perspectives in diagnostics and personalized treatment in diverse domains of neurology are given.

• Klíčová slova
• Alzheimer’s disease, Biomarker, Multiple sclerosis, Neuro-oncology, Parkinson’s disease, Personalized medicine, Predictive preventive personalized medicine, Stroke,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH