Roztroušená skleróza (RS) je chronické a nevyléčitelné autoimunitní onemocnění centrálního nervového systému (CNS). Cílem chorobu­ modifikující léčby (DMT - disease modifying therapy) je zpomalit progresi onemocnění, zabránit relapsům a zvýšit celkovou kvalitu života pacienta. Adherence označuje míru spolupráce pacienta při léčbě a je nezbytná pro účinnou léčbu. Non-adherence je spojená s rizikem progrese disability a se zvýšenými náklady na zdravotní péči. Cílem tohoto článku je představení tří kazuistik pacientů s vysoce účinnou terapií (HET - high efficacy therapy). První pacientka je léčena HET od počátku choroby a má výbornou adherenci. Druhá kazuistika referuje o pacientce s non­‐adherencí na interferonu beta s následnou těžkou atakou po vysazení léčby. Pacientka je nyní stabilizovaná na ocrelizumabu. Třetí pacientka měla nežádoucí účinky na perorální léčbě dimethyl fumarátem a byla také převedena na ocrelizumab.

Multiple sclerosis (MS) is a chronic and incurable autoimmune disease of the central nervous system (CNS). The goals of disease-modifying therapy (DMT) are to slow down disease progression, prevent relapses, and increase the overall quality of life of the patient. Adherence refers to the degree to which a patient complies with prescribed treatment and as such is required for the treatment to be effective. Non-adherence is associated with a risk of disability progression and increased healthcare costs. The aim of the article is to present three case reports of female patients on high-efficacy therapy (HET). Patient 1 has been treated with HET since disease onset and has excellent adherence. The second case report presents a patient with non-adherence to interferon beta with a subsequent severe attack following treatment discontinuation. The patient is now stabilized with ocrelizumab. Patient 3 had experienced adverse effects while on oral treatment with dimethyl fumarate and was also switched to ocrelizumab.

• Keywords
• ocrelizumab,
• MeSH
• Medication Adherence statistics & numerical data   MeSH
• Dimethyl Fumarate adverse effects   therapeutic use   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * economics   therapeutic use   MeSH
• Immunologic Factors economics   therapeutic use   MeSH
• Interferon-beta adverse effects   therapeutic use   MeSH
• Administration, Intravenous MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Young Adult MeSH
• Multiple Sclerosis * diagnostic imaging   drug therapy   pathology   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Roztroušená skleróza (RS) je chronické autoimunitní a neurodegenerativní onemocnění postihující mozek a míchu. Onemocnění začíná nejčastěji mezi 20.-30. rokem věku a vyskytuje se třikrát častěji u žen. Léčbu je nutné zahájit co nejdříve po stanovení diagnózy. U pacientek ve fertilním věku je vhodné zvolit lék, jehož podávání je bezpečné i po početí.

Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease affecting the brain and spinal cord. Most often the disease begins between the ages of 20-30 and occurs three times as often in women. Treatment is initiated early, preferably after the first symptom of the disease. In patients of childbearing age, it is advisable to choose a drug that is safe after conception. The period of pregnancy has a favourable effect on the course of the disease, with a decrease in activity in most cases. In stable patients, therapy is discontinued. If patients have unplanned pregnancy and the disease is not stable, therapy with certain drugs can be continued. This communication gives an overview of the drugs that can be given not only during pregnancy but also during lactation. The procedures used in the care of women after childbirth and during lactation are mentioned. Stabilized patients are assured of safe therapy during this time and can continue breastfeeding for 4-6 months. Other drugs from both the first and escalation lines do not yet have a proven safety profile during pregnancy or lactation and are therefore not mentioned in the article.

• MeSH
• Glatiramer Acetate adverse effects   therapeutic use   MeSH
• Interferon-beta adverse effects   therapeutic use   MeSH
• Breast Feeding MeSH
• Pregnancy Complications * MeSH
• Humans MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Review MeSH

Roztroušená skleróza a psoriáza jsou autoimunitní onemocnění s určitými společnými imunopatologickými rysy. Byť není zatím jednoznačně prokázáno, že by byla koincidence těchto onemocnění vyšší, většina metaanalýz tomu nasvědčuje. V současné době je v České republice schválen v léčbě pouze jeden preparát, u kterého byla prokázána účinnost u obou těchto onemocnění, a tím je dimethyl-fumarát. Bezpečnost a možný pozitivní efekt na obě onemocnění byly prokázány u secukinumabu a ustekinumabu, které ale nejsou schváleny k léčbě roztroušené sklerózy. V případě středně těžké či těžké psoriázy s nutností systémové léčby je možné v léčbě roztroušené sklerózy zahájit léčbu glatiramer-acetátem, který nemá imunosupresivní efekt a má nízké riziko interakcí s biologickou léčbou. V přídatné léčbě s interferonem beta byla prokázána i bezpečnost methotrexátu, který lze užít v systémové léčbě psoriázy. Vhodné je užití fototerapie, která zvyšuje hladinu vitaminu D. Nevhodné jsou u pacientů s demyelinizačním onemocněním inhibitory tumor necrosis faktoru, u kterých existuje reálné riziko vyvolání či zhoršení demyelinizačního onemocnění jak periferního, tak i centrálního nervového systému. V případě těžkého průběhu psoriázy a roztroušené sklerózy (což se zdá být dle dostupných populačních studií relativně vzácný jev) je nutná spolupráce neurologa, dermatologa a imunologa vzhledem k riziku farmakodynamických interakcí při polyterapii imunomodulační léčby.

Multiple sclerosis and psoriasis are autoimmune diseases which share certain immunopathological features. Although the coincidence of the two diseases has not yet been clearly shown to be higher, most meta-analyses suggest so. In the Czech Republic, only one agent is currently approved in the treatment for which efficacy in both diseases has been demonstrated: dimethyl fumarate. Safety and a possible positive effect on both diseases have been demonstrated in secukinumab and ustekinumab which, however, are not approved to treat multiple sclerosis. In the case of moderate or severe psoriasis requiring systemic treatment, it is possible - in treating multiple sclerosis - to initiate treatment with glatiramer acetate which has no immunosuppressive effect and exhibits a low risk of interactions with biological therapy. In adjunctive therapy with interferon beta, the safety of methotrexate has been shown, which can also be used in the systemic treatment of psoriasis. It is advisable to use phototherapy which increases the level of vitamin D. In patients with demyelinating disease, tumour necrosis factor inhibitors are unsuitable since there is a real risk of inducing or deteriorating demyelinating disease in both the peripheral and central nervous systems. In the case of a severe course of both psoriasis and multiple sclerosis (which, according to available population studies, appears to be a relatively rare phenomenon), cooperation of a neurologist, dermatologist, and immunologist is required given the risk of pharmacodynamic interactions in the case of polytherapy involving immunomodulatory treatment.

• Keywords
• secukinumab,
• MeSH
• Dimethyl Fumarate therapeutic use   MeSH
• Phototherapy methods   MeSH
• Glatiramer Acetate adverse effects   MeSH
• Immunologic Factors therapeutic use   MeSH
• Immunomodulation MeSH
• Interferon-beta adverse effects   MeSH
• Comorbidity MeSH
• Drug Interactions MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Psoriasis * drug therapy   complications   MeSH
• Multiple Sclerosis * diagnosis   drug therapy   complications   MeSH
• Tumor Necrosis Factor-alpha antagonists & inhibitors   MeSH
• Ustekinumab therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Zvýšená incidence bolestí hlavy u pacientů s roztroušenou sklerózou (RS) ve srovnání se zdravou populací je obecně známa. Prevalence v jednotlivých studiích, v jejich meta-analýzách a v jednotlivých publikovaných souborech pacientů má velký rozptyl 4-64 %. Ukazuje se, že je zvýšený výskyt bolestí hlavy v časné fázi RS a v průběhu relapsu je pravděpodobně ekvivalentem zánětlivé reakce na meningách u pacientů s RS. V tomto smyslu mohou být bolesti hlavy (migréna nebo tenzní typ bolestí hlavy - TTH) chápány jako symptom RS. Několik léků používaných v léčbě RS může způsobit bolesti hlavy nebo dekompenzovat migrénu, zhoršit kvalitu života a lékovou adherenci. V případě klasifikace primární bolesti hlavy jako komorbidity RS je nutno zahájit specifickou léčbu.

The increased incidence of headache in MS patients compared to a healthy population is generally known. Prevalence in individual studies, in their meta-analyses and in individual published MS patient populations has a large dispersion of 4-64 %. It turns out that there is an increased incidence of headache in the early stage of MS and during relapse and are likely equivalent to an inflammatory reaction on meninges in MS patients. In this sense, headaches, migraine or a tension type of headache (TTH) can be understood as a symptom of MS. Several drugs used in the treatment of MS can cause headaches or decompensate migraine, worsen quality of life and drug adherence. In the case of classification of primary headache as comorbidity of MS, specific treatment should be initiated.

• MeSH
• Headache chemically induced   diagnosis   epidemiology   etiology   classification   MeSH
• Diagnosis, Differential MeSH
• Interferon-beta administration & dosage   adverse effects   MeSH
• Comorbidity MeSH
• Humans MeSH
• Migraine Disorders * chemically induced   diagnosis   epidemiology   etiology   classification   MeSH
• Multiple Sclerosis * diagnosis   complications   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Sclerosis multiplex (SM) je autoimunitné ochorenie centrálneho nervového systému. V súčasnosti máme k dispozícii pomerne širokú škálu ochorenie modifikujúcich liečiv (Disease Modifying Therapy - DMT) s rôznym mechanizmom účinku a účinnosťou. Na dosiahnutie čo najlepšieho liečebného ovplyvnenia ochorenia je potrebný individuálny prístup pri výbere liečby. Je potrebné mať na pamäti aj riziká zvolenej liečby pre daného pacienta. Kontinuálne klinické, ako aj laboratórne monitorovanie pacientov je nevyhnutné.

Currently, we have a fairly wide range of disease - modifying drugs (DMD) with different mechanisms of action and different efficiencies. To obtain the most efficient therapeutic results we need to choose an individual approach for appropriate therapy. It is also very important to keep in mind the risk of this therapy for appropriate patient. The continual clinical and laboratory monitoring of the patients is unavoidable.

• MeSH
• Alemtuzumab pharmacology   adverse effects   therapeutic use   MeSH
• Dimethyl Fumarate pharmacology   adverse effects   therapeutic use   MeSH
• Glatiramer Acetate pharmacology   adverse effects   therapeutic use   MeSH
• Risk Assessment MeSH
• Antibodies, Monoclonal, Humanized pharmacology   adverse effects   therapeutic use   MeSH
• Immunosuppressive Agents pharmacology   adverse effects   therapeutic use   MeSH
• Interferon-beta pharmacology   adverse effects   therapeutic use   MeSH
• Cladribine pharmacology   adverse effects   therapeutic use   MeSH
• Crotonates pharmacology   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Natalizumab pharmacology   adverse effects   therapeutic use   MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Toluidines pharmacology   adverse effects   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Background: Neutralizing anti-drug antibodies (ADA) can greatly reduce the efficacy of biopharmaceuticals used to treat patients with multiple sclerosis (MS). However, the biological factors pre-disposing an individual to develop ADA are poorly characterized. Thus, there is an unmet clinical need for biomarkers to predict the development of immunogenicity, and subsequent treatment failure. Up to 35% of MS patients treated with beta interferons (IFNβ) develop ADA. Here we use machine learning to predict immunogenicity against IFNβ utilizing serum metabolomics data. Methods: Serum samples were collected from 89 MS patients as part of the ABIRISK consortium-a multi-center prospective study of ADA development. Metabolites and ADA were quantified prior to and after IFNβ treatment. Thirty patients became ADA positive during the first year of treatment (ADA+). We tested the efficacy of six binary classification models using 10-fold cross validation; k-nearest neighbors, decision tree, random forest, support vector machine and lasso (Least Absolute Shrinkage and Selection Operator) logistic regression with and without interactions. Results: We were able to predict future immunogenicity from baseline metabolomics data. Lasso logistic regression with/without interactions and support vector machines were the most successful at identifying ADA+ or ADA- cases, respectively. Furthermore, patients who become ADA+ had a distinct metabolic response to IFNβ in the first 3 months, with 29 differentially regulated metabolites. Machine learning algorithms could also predict ADA status based on metabolite concentrations at 3 months. Lasso logistic regressions had the greatest proportion of correct classifications [F1 score (accuracy measure) = 0.808, specificity = 0.913]. Finally, we hypothesized that serum lipids could contribute to ADA development by altering immune-cell lipid rafts. This was supported by experimental evidence demonstrating that, prior to IFNβ exposure, lipid raft-associated lipids were differentially expressed between MS patients who became ADA+ or remained ADA-. Conclusion: Serum metabolites are a promising biomarker for prediction of ADA development in MS patients treated with IFNβ, and could provide novel insight into mechanisms of immunogenicity.

• MeSH
• Biomarkers blood   MeSH
• Interferon-beta adverse effects   therapeutic use   MeSH
• Leukocytes, Mononuclear immunology   metabolism   MeSH
• Humans MeSH
• Membrane Lipids metabolism   MeSH
• Membrane Microdomains MeSH
• Metabolome * MeSH
• Metabolomics * methods   MeSH
• Antibodies, Neutralizing blood   immunology   MeSH
• Prognosis MeSH
• Antibodies blood   immunology   MeSH
• Multiple Sclerosis blood   diagnosis   drug therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Roztroušená skleróza je chronické autoimunitní onemocnění centrálního nervového systému, u kterého vedou zánětlivé procesy k poškozením myelinu a ke ztrátě axonů a neuronů a jehož důsledkem je trvalá invalidita. První ataka onemocnění se typicky manifestuje mezi 20. a 40. rokem života a u většiny nemocných je průběh roztroušené sklerózy relaps-remitentní. V současnosti je pro pacienty s relaps-remitentní formou roztroušené sklerózy dostupná imunomodulační léčba, která, pokud je podána včas, snižuje aktivitu nemoci a oddaluje nástup tzv. sekundární progrese. Při volbě léčebného přípravku se snažíme o nasazení účinné terapie za minimalizace možných rizik léčby, které jsou dané typem léku a do jisté míry jsou i individuální.

Multiple sclerosis is a chronic autoimmune disease of the central nervous system that is characterized by inflammatory processes that can lead to demyelination and loss of axons and neurons, which is major cause of permanent disability. Multiple sclerosis usually begins around the age between 20 and 40 years and disease course is typically relapsing-remitting. Disease modifying drugs are a group of treatments for people with relapsing MS that reduce the disease activity and can delay an onset of the secondary progressive phase. We weigh benefits against risks of each kind of drug for each individual patient before we consider prescribing disease modifying drugs.

• Keywords
• Ocrevus (ocrelizumab), Lemtrada (alemtuzumab),
• MeSH
• Alemtuzumab administration & dosage   adverse effects   MeSH
• Early Diagnosis MeSH
• Fingolimod Hydrochloride administration & dosage   adverse effects   MeSH
• Glatiramer Acetate administration & dosage   adverse effects   MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   adverse effects   MeSH
• Remission Induction MeSH
• Interferon-beta administration & dosage   adverse effects   MeSH
• Cladribine administration & dosage   adverse effects   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Natalizumab administration & dosage   adverse effects   MeSH
• Multiple Sclerosis, Relapsing-Remitting drug therapy   MeSH
• Multiple Sclerosis * diagnostic imaging   drug therapy   classification   MeSH
• Secondary Prevention MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

V posledních 15 letech byl v mezinárodních a kooperativních studiích identifikován zvýšený počet genetických a environmentálních rizikových faktorů pro roztroušenou sklerózu (RS) u dětí, které přispěly k lepšímu chápání patofyziologie RS. Za rizikové faktory RS u dětí jsou považovány puberta a pohlavní hormony, obezita, hladina vitaminu D, expozice virům, kouření, složení stravy a genetické faktory. Diagnostika musí být rozšířena o vyloučení ostatních zánětlivých onemocnění. Ne z každé demyelinizační příhody u dětí se vyvine RS. Je nutná pečlivá diferenciální diagnostika. Léčba klinicky izolovaného syndromu nebo akutní exacerbace, resp. relapsu RS u dětí vychází ze zkušeností s léčbou u dospělých. Nedostatečná účinnost léčby 1. linie léky ovlivňujícími nemoc (DMD – disease modifying drugs) vyžaduje eskalaci u více než 40 % dětských pacientů. Neoddělitelnou součástí léčby RS u dětí a adolescentů je léčba symptomatická a nemedikamentózní.

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• Keywords
• PARADIGMS,
• MeSH
• Diagnosis, Differential MeSH
• Child MeSH
• Fingolimod Hydrochloride adverse effects   therapeutic use   MeSH
• Interferon-beta adverse effects   therapeutic use   MeSH
• Humans MeSH
• Methylprednisolone administration & dosage   MeSH
• Adolescent MeSH
• Multicenter Studies as Topic MeSH
• Randomized Controlled Trials as Topic MeSH
• Risk Factors MeSH
• Multiple Sclerosis diagnosis   drug therapy   MeSH
• Statistics as Topic MeSH
• Age Factors MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Review MeSH

Roztroušená skleróza představuje nejčastější imunopatologické onemocnění centrálního nervového systému a zároveň nejčastější neurologickou příčinu invalidity mladých osob v našem regionu. První lék se schopností modifikovat průběh atakovité (relabující‑remitující) formy choroby – interferon beta ‒ byl uveden do praxe v roce 1993. V současnosti zahrnuje skupina těchto léčiv více než deset přípravků a jejich řada se stále rozrůstá. Dosud posledním registrovaným přípravkem je monoklonální protilátka okrelizumab (Ocrevus), který jako první lék prokázal jednoznačný efekt také u primárně progresivní formy roztroušené sklerózy. Článek podává základní informace o účinnosti, bezpečnosti a indikacích k léčbě okrelizumabem u roztroušené sklerózy, včetně prvních zkušeností a důležitých otázek z klinické praxe.

Multiple sclerosis is the most frequent immunopathological disease of the central nervous system and also the most frequent neurological condition leading to the disability of young people in our region. First disease‑modifying drug treating the relapsing‑remitting form of the disease – interferon beta ‒ was introduced in 1993. Currently, the group of these drugs comprises more than ten medications and is still growing. The last registered drug is a monoclonal antibody ocrelizumab (Ocrevus) that, for the first time, proved to be effective also in the primary progressive form of multiple sclerosis. The article provides fundamental information about the efficacy, safety and indications of ocrelizumab treatment in multiple sclerosis, including initial experiences and important questions from the clinical practice.

• Keywords
• Okrelizumab,
• MeSH
• Autoimmune Diseases of the Nervous System diagnosis   etiology   therapy   MeSH
• B-Lymphocytes cytology   pathology   drug effects   MeSH
• Multiple Sclerosis, Chronic Progressive * diagnosis   drug therapy   MeSH
• Drug Therapy history   methods   trends   MeSH
• Antibodies, Monoclonal, Humanized * administration & dosage   adverse effects   therapeutic use   MeSH
• Interferon-beta administration & dosage   adverse effects   therapeutic use   MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Meta-Analysis as Topic MeSH
• Central Nervous System Diseases diagnosis   etiology   therapy   MeSH
• Multiple Sclerosis, Relapsing-Remitting diagnosis   drug therapy   MeSH
• Multiple Sclerosis * diagnosis   etiology   drug therapy   MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH

Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-β. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-β administration. Reduced monocyte NOTCH2 expression in nADA+ MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA+ patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-β administration.

• MeSH
• Biomarkers analysis   metabolism   MeSH
• Adult MeSH
• Interferon-beta adverse effects   immunology   MeSH
• Drug Hypersensitivity blood   diagnosis   immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Monocytes metabolism   MeSH
• Antibodies, Neutralizing blood   immunology   MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Prospective Studies MeSH
• Cross-Sectional Studies MeSH
• Receptor, Notch2 analysis   metabolism   MeSH
• Multiple Sclerosis blood   drug therapy   immunology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH