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.
- Publikační typ
- časopisecké články MeSH
- MeSH
- kladribin * aplikace a dávkování ekonomika farmakologie MeSH
- klinické rozhodování MeSH
- lidé MeSH
- monitorování léčiv metody statistika a číselné údaje MeSH
- roztroušená skleróza * farmakoterapie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- biologické markery krev MeSH
- intermediární filamenta * MeSH
- lidé MeSH
- roztroušená skleróza * krev prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Slovenská republika MeSH
BACKGROUND: Neurofilament light chain is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (MS). Its role in progressive MS is less clear. AIM: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA-3 (No Evident Disease Activity), and brain volumetry, in a cohort of patients with the progressive disease form (PMS). METHODS: Levels of pNfL (SIMOA technology) were examined in 52 PMS patients and analysed in relationship to NEDA-3 status and annual brain volume loss (BVL) during the last 12 months. The statistical model was developed using logistic regression analysis, including demographic, clinical and magnetic resonance imaging (MRI) data as independent variables. Dependent variables were NEDA-3 status and BVL. RESULTS: The mean age of the study participants (n=52, 50% females) was 45.85 (SD, 9.82) and the median disability score was 5.0 (IQR: 5.0-5.5). ROC analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 77.8% and 87.6%, respectively, P<0.001) and abnormal BVL (the sensitivity and specificity were 96.6% and 68.2%, respectively, P<0.001). CONCLUSIONS: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-3 status, including brain MRI-volumetry, in patients with the progressive form of MS.
- MeSH
- atrofie MeSH
- biologické markery MeSH
- intermediární filamenta MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mozek diagnostické zobrazování patologie MeSH
- nemoci centrálního nervového systému * MeSH
- progrese nemoci MeSH
- relabující-remitující roztroušená skleróza * diagnostické zobrazování farmakoterapie patologie MeSH
- roztroušená skleróza * diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS. METHODS: This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration's Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS. RESULTS: The 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35' and 56°16') were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes <40°, more severe disease was associated with higher latitudes (β = 0.08, 95% CI 0.04-0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40° (β = -0.02, 95% CI -0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 years (β = - 0.5, 95% CI -0.6 to 0.4) and 18 years (β = - 0.6, 95% CI -0.7 to 0.4), as well as with lower lifetime UVB exposure at the time of disability assessment (β = -1.0, 95% CI -1.1 to 0.9). DISCUSSION: In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.
- MeSH
- lidé MeSH
- posuzování pracovní neschopnosti MeSH
- registrace MeSH
- roztroušená skleróza * diagnóza epidemiologie MeSH
- stupeň závažnosti nemoci MeSH
- ultrafialové záření škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
INTRODUCTION: There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). METHODS: Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). RESULTS: Levels of pNfL were significantly higher in MS patients than in healthy controls (p < 0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (p < 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, p < 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, p < 0.001). CONCLUSION: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.
- MeSH
- biologické markery MeSH
- intermediární filamenta MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek MeSH
- relabující-remitující roztroušená skleróza * MeSH
- ROC křivka MeSH
- roztroušená skleróza * diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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 farmakologie škodlivé účinky terapeutické užití MeSH
- dimethyl fumarát farmakologie škodlivé účinky terapeutické užití MeSH
- glatiramer acetát farmakologie škodlivé účinky terapeutické užití MeSH
- hodnocení rizik MeSH
- humanizované monoklonální protilátky farmakologie škodlivé účinky terapeutické užití MeSH
- imunosupresiva farmakologie škodlivé účinky terapeutické užití MeSH
- interferon beta farmakologie škodlivé účinky terapeutické užití MeSH
- kladribin farmakologie škodlivé účinky terapeutické užití MeSH
- krotonáty farmakologie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- natalizumab farmakologie škodlivé účinky terapeutické užití MeSH
- nežádoucí účinky léčiv MeSH
- roztroušená skleróza * farmakoterapie MeSH
- toluidiny farmakologie škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
