BACKGROUND: Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. OBJECTIVES: To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. DESIGN: A multicentre, prospective, non-controlled, non-interventional, observational cohort study. METHODS: Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. RESULTS: A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (p-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668). CONCLUSION: The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.

• Publication type
• Journal Article MeSH

Sekundárně progresivní roztroušená skleróza (SP-RS) představuje druhou nejčastější formu roztroušené sklerózy. Je pro ni charakteristické plynulé zhoršování neurologických obtíží s přítomností pouze ojedinělých relapsů nebo jejich úplnou absencí. Účinný lék pro pacienty se SP-RS na evropském trhu dlouho chyběl. Siponimod, selektivní modulátor sfingosin-1-fosfátových receptorů, je prvním přípravkem, u kterého bylo prokázáno zpomalení klinicky potvrzené progrese. Kazuistika popisuje téměř 19leté období ženy léčené pro roztroušenou sklerózu.

Secondary progressive multiple sclerosis (SP-MS) is the second most common form of multiple sclerosis. It is characterized by insidious worsening of neurologic function over time, with the reduction in the frequency of relapses or complete absence of relapse activity. An effective treatment for patients with SP-MS was lacking on the European market for a long time. Siponimod, a selective modulator of sfingosin-1-phosphate receptors, is the first drug to treat SP-MS, that showed a significant decrease in disability progression. A case study describes almost 19-year period of woman treated with multiple sclerosis.

• Keywords
• siponimod, neurodeficit,
• MeSH
• Azetidines therapeutic use   MeSH
• Benzyl Compounds therapeutic use   MeSH
• Multiple Sclerosis, Chronic Progressive * diagnosis   drug therapy   complications   pathology   MeSH
• Adult MeSH
• Humans MeSH
• Disease Progression MeSH
• Receptors, Lysosphingolipid drug effects   MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Roztroušená skleróza (RS) je závažné a chronické neurologické onemocnění, které může způsobit významnou invaliditu. Sekundárně progresivní RS (SPRS) je charakterizována kontinuálním zhoršováním neurologických funkcí s přítomností ojedinělých relapsů nebo bez nich. V březnu 2019 byl americkým Food and Drug Agency (FDA) schválen přípravek siponimod k léčbě SPRS s aktivitou onemocnění. Siponimod je první perorální lék pro SPRS s aktivitou onemocnění významně ovlivňující progresi disability a patologické změny v mozkové tkáni. Jedná se o modulátor receptoru pro sfingosin 1-fosfát (S1P) novější generace, který ovlivňuje receptory S1P1, čímž inhibuje vyplavování lymfocytů z lymfatických uzlin a thymu.

Multiple sclerosis (MS) is a serious and chronic neurological disease that can cause significant disability. Secondary progressive MS (SPMS) is characterized by continuous deterioration of neurological function with or without sporadic relapses. In March 2019, siponimod was approved by the US Food and Drug Agency (FDA) for the treatment of SPMS with disease activity. Siponimod is the first oral drug for the treatment of SPMS with disease activity significantly affecting the progression of disability and pathological changes in brain tissue. This is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator that internalizes S1P1 receptors, thereby inhibiting efflux of lymphocytes from lymph nodes and thymus.

• Keywords
• siponimod,
• MeSH
• Multiple Sclerosis, Chronic Progressive * diagnosis   drug therapy   MeSH
• Clinical Studies as Topic MeSH
• Contraindications, Drug MeSH
• Humans MeSH
• Medication Therapy Management MeSH
• Drug-Related Side Effects and Adverse Reactions classification   MeSH
• Disease Progression MeSH
• Sphingosine-1-Phosphate Receptors * agonists   administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease where cells in the central nervous system play a critical role. To our knowledge, alemtuzumab, fumarates (dimethyl, diroximel, and monomethyl), glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and teriflunomide are either limited to the periphery or insufficiently studied to confirm direct central nervous system effects in participants with multiple sclerosis. In contrast, cladribine and sphingosine 1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are central nervous system-penetrant and could have beneficial direct central nervous system properties.

• MeSH
• Immunosuppressive Agents MeSH
• Cladribine MeSH
• Humans MeSH
• Central Nervous System Diseases * MeSH
• Multiple Sclerosis, Relapsing-Remitting * MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Za poslední dekády se scénář léčby roztroušené sklerózy (RS) radikálně změnil. Rostoucí dostupnost účinné terapie modifikující chorobu (DMT) posunula terapeutické cíle od snížení počtu relapsů a nárůstu invalidity až k absenci známek aktivity onemocnění jak klinických, tak na magnetické rezonanci. Volba terapie je stále složitější a měla by se řídit odpovídajícími znalostmi mechanismu účinku jednotlivých léků, účinností a jejich bezpečnostním profilem. Vzhledem k tomu, že DMT ovlivňují zejména zánětlivou složku nemoci dominující v počátcích RS, časné zahájení léčby je klíčové. Recentní doporučení se kloní k časnému zahájení terapie s vyšší účinností. Využití skupiny modulátorů S1P receptorů jako léků první volby v léčbě RS by tak mohlo vést ke stabilizaci většího počtu pacientů již od počátku nemoci, a tím ke zlepšení jejich dlouhodobé prognózy.

Over the last decades, the scenario of multiple sclerosis (MS) treatment has changed radically. The increasing availability of effective disease-modifying therapies (DMTs) has shifted therapeutic targets from a reduction in relapses and increase in disability to the absence of signs of disease activity both clinically and on MRI. The choice of therapy is increasingly complex and should be guided by adequate knowledge of the mechanism of action of each drug, its efficacy and safety profile. Since DMTs mainly affect the inflammatory component of the disease predominant in early MS, early initiation of treatment is crucial. Recent recommendations lean towards early initiation of therapy with higher efficacy. Thus, the use of the S1P receptor modulator family of drugs as the first choice in the treatment of MS could lead to the stabilization of more patients from the onset of the disease and thus improve their long-term prognosis.

• Keywords
• ozanimod, ponesimod, siponimod,
• MeSH
• Antirheumatic Agents administration & dosage   therapeutic use   MeSH
• Azetidines administration & dosage   therapeutic use   MeSH
• Benzyl Compounds therapeutic use   MeSH
• Fingolimod Hydrochloride administration & dosage   adverse effects   therapeutic use   MeSH
• Inflammatory Bowel Diseases drug therapy   MeSH
• Indans administration & dosage   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Sphingosine 1 Phosphate Receptor Modulators * administration & dosage   adverse effects   therapeutic use   MeSH
• Oxadiazoles therapeutic use   MeSH
• Multiple Sclerosis drug therapy   MeSH
• Thiazoles administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH

Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system (CNS). Currently, MS treatment is limited to several Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved medications that slow disease progression by immunomodulatory action. Fingolimod and siponimod have similar mechanisms of action, and consequently, their therapeutic effects may be comparable. However, while fingolimod is mainly used for relapsing-remitting MS (RRMS), siponimod, according to EMA label, is recommended for active secondary progressive MS (SPMS). Clinicians and scientists are analysing whether patients can switch from fingolimod to siponimod and identifying the advantages or disadvantages of such a switch from a therapeutic point of view. In this review, we aim to discuss the therapeutic effects of these two drugs and the advantages/disadvantages of switching treatment from fingolimod to siponimod in patients with the most common forms of MS, RRMS and SPMS.

• MeSH
• Multiple Sclerosis, Chronic Progressive * drug therapy   chemically induced   MeSH
• Fingolimod Hydrochloride adverse effects   MeSH
• Risk Assessment MeSH
• Immunosuppressive Agents adverse effects   MeSH
• Humans MeSH
• Neurodegenerative Diseases * chemically induced   drug therapy   MeSH
• Recurrence MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Siponimod signifikantně snižuje riziko potvrzené progrese disability, zhoršení kognitivního výkonu, snižuje riziko relapsů a příznivě ovlivňuje parametry magnetické rezonance hodnocené pomocí atrofie mozku či zánětlivých ložisek u pacientů se sekundárně progresivní roztroušenou sklerózou. Data z pětileté extenze studie EXPAND podporují význam časné detekce sekundárně progresivní roztroušené sklerózy a tedy včasného zahájení léčby siponimodem.

Siponimod significantly reduced the risk of confirmed disability progression, worsening in cognitive processing speed, relapses, and magnetic resonance imaging measures of brain atrophy and inflammation in secondary progressive multiple sclerosis patients. Data from the 5-year extension of the EXPAND study support the importance of early detection of secondary progressive multiple sclerosis and thus early initiation of siponimod treatment.

• Keywords
• siponimod,
• MeSH
• Early Diagnosis MeSH
• Kaplan-Meier Estimate MeSH
• Humans MeSH
• Sphingosine 1 Phosphate Receptor Modulators * administration & dosage   economics   pharmacology   MeSH
• Brain drug effects   MeSH
• Numbers Needed To Treat MeSH
• Disease Progression MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

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• Keywords
• studie EXPAND, siponimod,
• MeSH
• Multiple Sclerosis, Chronic Progressive * diagnosis   drug therapy   MeSH
• Cytochrome P-450 CYP2C9 analysis   genetics   MeSH
• Clinical Studies as Topic MeSH
• Middle Aged MeSH
• Humans MeSH
• Disease Progression MeSH
• Sphingosine-1-Phosphate Receptors antagonists & inhibitors   therapeutic use   MeSH
• Multiple Sclerosis diagnosis   drug therapy   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Publikace obsahuje práce přednesené na kongresu, který se zaměřil na neurologické nemoci. Určeno odborné veřejnosti.

• MeSH
• Nervous System Diseases MeSH
• Publication type
• Congress MeSH
• Collected Work MeSH
• News MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurologie

• Keywords
• studie EXPAND, Siponimod,
• MeSH
• Azetidines therapeutic use   MeSH
• Benzyl Compounds therapeutic use   MeSH
• Multiple Sclerosis, Chronic Progressive * drug therapy   MeSH
• Double-Blind Method MeSH
• Humans MeSH
• Sphingosine 1 Phosphate Receptor Modulators MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Trial, Phase III MeSH
• Randomized Controlled Trial MeSH