INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• autoprotilátky krev   MeSH
• činnosti denního života MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory cholinergní * imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND AND OBJECTIVES: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). METHODS: ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population. RESULTS: Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed. DISCUSSION: Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.

• MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• imunologické faktory * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   diagnostické zobrazování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH

• MeSH
• bakteriální lyzáty * farmakologie   klasifikace   terapeutické užití   MeSH
• BCG vakcína aplikace a dávkování   farmakologie   imunologie   terapeutické užití   MeSH
• glukany aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• imunologické faktory farmakologie   klasifikace   terapeutické užití   MeSH
• imunomodulační látky * aplikace a dávkování   farmakologie   klasifikace   terapeutické užití   MeSH
• mikrobiota fyziologie   imunologie   MeSH
• probiotika farmakologie   klasifikace   terapeutické užití   MeSH
• slizniční imunita imunologie   účinky léků   MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Natalizumab was not shown to modify disability in progressive multiple sclerosis (MS). This matched observational study compared the effectiveness of autologous haematopoietic stem cell transplantation (AHSCT) with natalizumab in progressive MS. METHODS: Patients with primary/secondary progressive MS from seven AHSCT MS centres and the MSBase registry, treated with AHSCT or natalizumab, were matched on a propensity score derived from sex, age, Expanded Disability Status Scale (EDSS), number of relapses 12/24 months before baseline, time from MS onset, the most effective prior therapy and country. The pairwise-censored groups were compared on hazards of 6-month confirmed EDSS worsening and improvement, relapses and annualised relapse rates (ARRs), using Andersen-Gill proportional hazards models and conditional negative binomial model. RESULTS: 39 patients treated with AHSCT (37 with secondary progressive MS, mean age 37 years, EDSS 5.7, 28% with recent disability progression, ARR 0.54 during the preceding year) were matched with 65 patients treated with natalizumab. The study found no evidence for difference in hazards of confirmed EDSS worsening (HR 1.49, 95% CI 0.70 to 3.14) and improvement (HR 1.50, 95% CI 0.22 to 10.29) between AHSCT and natalizumab over up to 4 years. The relapse activity was also similar while treated with AHSCT and natalizumab (ARR: mean±SD 0.08±0.28 vs 0.08±0.25; HR 1.05, 95% CI 0.39 to 2.82). In the AHSCT group, 3 patients experienced febrile neutropenia during mobilisation, 9 patients experienced serum sickness, 6 patients required intensive care unit admission and 36 patients experienced complications after discharge. No treatment-related deaths were reported. CONCLUSION: This study does not support the use of AHSCT to control disability in progressive MS with advanced disability and low relapse activity.

• MeSH
• autologní transplantace * MeSH
• chronicko-progresivní roztroušená skleróza * farmakoterapie   terapie   MeSH
• dospělí MeSH
• imunologické faktory terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• natalizumab * terapeutické užití   MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH

BACKGROUND: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. METHODS: Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). RESULTS: A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. CONCLUSION: In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

• MeSH
• glatiramer acetát * terapeutické užití   MeSH
• humanizované monoklonální protilátky * terapeutické užití   škodlivé účinky   MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   MeSH
• interferony terapeutické užití   škodlivé účinky   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• recidiva MeSH
• registrace MeSH
• roztroušená skleróza farmakoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

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.

• Klíčová slova
• ocrelizumab,
• MeSH
• adherence k farmakoterapii statistika a číselné údaje   MeSH
• dimethyl fumarát škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * ekonomika   terapeutické užití   MeSH
• imunologické faktory ekonomika   terapeutické užití   MeSH
• interferon beta škodlivé účinky   terapeutické užití   MeSH
• intravenózní podání MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• roztroušená skleróza * diagnostické zobrazování   farmakoterapie   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• Klíčová slova
• ocrelizumab,
• MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunologické faktory terapeutické užití   MeSH
• klinická studie jako téma MeSH
• kongresy jako téma MeSH
• lidé MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• zprávy MeSH

BACKGROUND AND OBJECTIVES: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). METHODS: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. RESULTS: Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. DISCUSSION: Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.

• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dospělí MeSH
• gadolinium MeSH
• imunologické faktory terapeutické užití   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• natalizumab * terapeutické užití   MeSH
• neurofilamentové proteiny * krev   MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci MeSH
• relabující-remitující roztroušená skleróza krev   farmakoterapie   diagnostické zobrazování   MeSH
• roztroušená skleróza krev   diagnostické zobrazování   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Probiotics or bacteriotherapy is today's hot issue for public entities (Food and Agriculture Organization, and World Health Organization) as well as health and food industries since Metchnikoff and his colleagues hypothesized the correlation between probiotic consumption and human's health. They contribute to the newest and highly efficient arena of promising biotherapeutics. These are usually attractive in biomedical applications such as gut-related diseases like irritable bowel disease, diarrhea, gastrointestinal disorders, fungal infections, various allergies, parasitic and bacterial infections, viral diseases, and intestinal inflammation, and are also worth immunomodulation. The useful impact of probiotics is not limited to gut-related diseases alone. Still, these have proven benefits in various acute and chronic infectious diseases, like cancer, human immunodeficiency virus (HIV) diseases, and high serum cholesterol. Recently, different researchers have paid special attention to investigating biomedical applications of probiotics, but consolidated data regarding bacteriotherapy with a detailed mechanistically applied approach is scarce and controversial. The present article reviews the bio-interface of probiotic strains, mainly (i) why the demand for probiotics?, (ii) the current status of probiotics, (iii) an alternative to antibiotics, (iv) the potential applications towards disease management, (v) probiotics and industrialization, and (vi) futuristic approach.

• MeSH
• Bacteria * účinky léků   MeSH
• gastrointestinální nemoci terapie   imunologie   mikrobiologie   MeSH
• imunologické faktory terapeutické užití   MeSH
• imunomodulace MeSH
• lidé MeSH
• management nemoci MeSH
• probiotika * terapeutické užití   aplikace a dávkování   MeSH
• sekundární metabolismus MeSH
• střevní mikroflóra MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• fytoterapie * metody   MeSH
• imunologické faktory klasifikace   terapeutické užití   MeSH
• infekce dýchací soustavy * farmakoterapie   imunologie   patofyziologie   MeSH
• lidé MeSH
• mukociliární clearance fyziologie   účinky léků   MeSH
• rostlinné extrakty farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH