Monoclonal antibodies have become a mainstay in the treatment of patients with relapsing multiple sclerosis (RMS) and provide some benefit to patients with primary progressive MS. They are highly precise by specifically targeting molecules displayed on cells involved in distinct immune mechanisms of MS pathophysiology. They not only differ in the target antigen they recognize but also by the mode of action that generates their therapeutic effect. Natalizumab, an [Formula: see text]4[Formula: see text]1 integrin antagonist, works via binding to cell surface receptors, blocking the interaction with their ligands and, in that way, preventing the migration of leukocytes across the blood-brain barrier. On the other hand, the anti-CD52 monoclonal antibody alemtuzumab and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab, and ublituximab work via eliminating selected pathogenic cell populations. However, potential adverse effects may be serious and can necessitate treatment discontinuation. Most importantly, those are the risk for (opportunistic) infections, but also secondary autoimmune diseases or malignancies. Monoclonal antibodies also carry the risk of infusion/injection-related reactions, primarily in early phases of treatment. By careful patient selection and monitoring during therapy, the occurrence of these potentially serious adverse effects can be minimized. Monoclonal antibodies are characterized by a relatively long pharmacologic half-life and pharmacodynamic effects, which provides advantages such as permitting infrequent dosing, but also creates disadvantages regarding vaccination and family planning. This review presents an overview of currently available monoclonal antibodies for the treatment of RMS, including their mechanism of action, efficacy and safety profile. Furthermore, we provide practical recommendations for risk management, vaccination, and family planning.

• Klíčová slova
• Alemtuzumab, Disease-modifying therapy, Monoclonal antibodies, Multiple sclerosis, Natalizumab, Ocrelizumab, Ofatumumab, Rituximab, Ublituximab,
• MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• natalizumab terapeutické užití   MeSH
• protinádorové látky imunologicky aktivní * terapeutické užití   MeSH
• řízení rizik MeSH
• roztroušená skleróza * terapie   MeSH
• těhotenství MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• monoklonální protilátky MeSH
• natalizumab MeSH
• protinádorové látky imunologicky aktivní * 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