Cohort Of Relapsing-remitting Multiple Sclerosis Patients Research Articles

An Association of Framingham Risk Score with Patient Determined Disease Steps in a Cohort of Relapsing-Remitting Multiple Sclerosis Patients: An Italian Real-World Monocentric Experience.

The associations between Multiple Sclerosis (MS) and cardiovascular diseases, drawn from epidemiological studies, have attracted much attention in recent years. The present study employed a monocentric, observational, retrospective cohort design. The primary objective of the study was to describe the Framingham Risk Score (FRS) rate in a cross-sectional analysis of our cohort of relapsing-remitting MS patients who are regularly followed up and, if applicable, to identify any association with the patient's Patient Determined Disease Steps (PDDS). Cardiovascular risk was classified as follows: low if the FRS is less than 10%, moderate if it is 10% to 19%, and high if it is 20% or higher. A total cohort of 229 patients was enrolled. The sample consists of 163 women (71.2%). FRS categories were distributed as follows: 97 (42.3%) patients had low FRS, 84 (36.7%) patients had moderate FRS, and 48 (21%) patients had high FRS. In the univariable ordinal regression analysis, one one-point increase in the PDDS scale was associated with a 24% risk of high FRS (vs. low) (proportional odds ratio [OR] =2.426, 95% confidence interval [CI] 1.660-3.545; p <.0001). The results were also confirmed by the EDSS score, with a point increase in the EDSS score associated with a 19% risk of high FRS (vs. low) (proportional OR =1.953, 95% CI 1.429-2.669-1.04; p <.0001). The FRS demonstrated an association with the patient's "perception of the disease" as indicated by the PDDS. Further studies with larger cohorts are needed to adequately address cardiovascular risk in life-threatening conditions, such as MS.

Patient-reported outcome measurements in a selective cohort of relapsing-remitting multiple sclerosis patients: relationships with physical disability, cognitive impairment, and MRI-derived metrics.

The added value of patient-reported outcome measures (PROMs) in addition to standard clinical outcome tools in the assessment of relapsing-remitting multiple sclerosis (RRMS) patients' status is increasingly recognized. PROMs facilitate the detection of hidden aspects of MS and help to integrate the patient's subjective experience of health-related quality of life (HRQoL) status and treatment satisfaction in a holistic way. However, the relationship between PROMs and clinical and cognitive status has been scarcely investigated up to now. To investigate the association of PROMs with physical and cognitive disability in a cohort of RRMS patients at initiation of a new disease-modifying treatment. In this cross-sectional bicenter study, 59 consecutive RRMS patients underwent neurological examination with EDSS assessment, comprehensive cognitive tests (BVMT-R, SDMT, CVLT-II) and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A cross-sectional logistic regression analysis was performed to find baseline correlates of cognitive impairment. Of the 59 RRMS patients (mean age 39 ± 9.8years, 79.7% female, median EDSS 2.0), 33 (56%) had cognitive impairment. While almost all dimensions of health, explored by PROMs, were impacted in the overall sample, no significant difference was observed in patients with and without cognitive impairment. All PROMs were significantly associated with EDSS (R = 0.37-0.55; p < 0.05), except for the psychological component of MSIS-29, BDI and DEX-Q scores. No significant correlation was found between PROMs and cognitive performances. The cross-sectional logistic regression analysis included age, gender (female), education, EDSS, hippocampus and FLAIR lesion volumes as significant predictors of cognitive impairment. The data highlight that PROMs provide valuable information on the well-being of PwMS closely paralleling the extent of MS-related disability, as measured by the EDSS. Additional research should determine the relevance of PROMs as longitudinal outcome measures.

VALIDATION OF THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS (BICAMS) IN A LARGE COHORT OF RELAPSING-REMITTING MS PATIENTS.

Cognitive impairment is one of the most frequently reported symptoms in persons with multiple sclerosis (MS). The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been recommended as a standardized international screening and monitoring tool for brief cognitive assessment. The aim of our study was to assess the reliability and validity of the Serbian version of the BICAMS. A total of 500 relapsing-remitting MS (RRMS) patients and 69 age-, gender- and education-matched healthy control (HC) subjects were examined. All participants performed the BICAMS test battery, which includes the oral version of the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test second edition (CVLT-II), and Brief Visuospatial Memory Test Revised (BVMTR). A randomly selected subset of patients were retested one to three weeks after baseline. Statistically significant differences between patients and HCs were evident on the SDMT and BVMTR (p<0.001). HCs had higher CVLT-II scores but this difference did not reach statistical significance (p=0.063). Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was found in 62.9% of MS patients. There were statistically significant correlations between BICAMS scores and age, education, EDSS and disease duration in patient sample. Test-retest reliability was confirmed with Pearson correlation coefficient of 0.70 in all measures. This study supported the reliability and validity of the Serbian BICAMS, although the CVLT-II version tested here lacked sensitivity to detect MS compared to healthy volunteers.

Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study).

IntroductionMultiple sclerosis (MS) patients of African descent have increased risk for disease progression and may be less responsive to disease-modifying therapy.MethodsPatients in the CARE-MS studies received alemtuzumab 12 mg/day [initial alemtuzumab treatment (IAT); baseline: 5 days; 12 months later: 3 days] or subcutaneous interferon beta-1a (SC IFNB-1a) 3 ×/week. Core study outcomes were compared between treatment groups. In the extension study CAMMS03409, SC IFNB-1a-treated patients switched to alemtuzumab [delayed alemtuzumab treatment (DAT)]. Data from IAT and DAT arms were pooled to assess outcomes through 6 years post alemtuzumab initiation; IAT patients had an additional 2 years of follow-up in TOPAZ.ResultsOf 1200 CARE-MS patients, 43 (4%) were of African descent (35 IAT; 8 DAT) and received alemtuzumab in the 2-year core and/or 6-year extension; 29 (67%) remained on study at the time of analysis (24 IAT patients completed year 8 post alemtuzumab; 5 DAT patients completed year 6 post alemtuzumab). In year 2, annualized relapse rate (ARR; 0.09 versus 0.42), percentage of patients with improved Expanded Disability Status Scale (EDSS; 18% versus 11%), 6-month confirmed disability improvement (CDI; 28% versus 13%), no evidence of disease activity (55% versus 13%), and cumulative brain volume loss (BVL; − 0.55% versus − 1.32%) favored alemtuzumab versus SC IFNB-1a. Alemtuzumab remained efficacious at year 6 (pooled IAT/DAT) and at year 8 (IAT only) post alemtuzumab (ARR: 0.15 and 0.30; improved EDSS: 17% and 25%; CDI: 47% and 55%; BVL: − 1.14% and − 0.70%, respectively). No safety signals were unique to this population.ConclusionsAlemtuzumab was efficacious in a small cohort of relapsing-remitting MS patients of African descent over 8 years. Safety was consistent with the overall CARE-MS population, although the small sample size may have prevented the detection of known low-frequency adverse events.ClinicalTrials.gov Registration NumbersCARE-MS I, II, extension, TOPAZ: NCT00530348, NCT00548405, NCT00930553, NCT02255656.FundingSanofi (Cambridge, MA, USA) and Bayer HealthCare Pharmaceuticals (Leverkusen, Germany).Electronic supplementary materialThe online version of this article (10.1007/s40120-019-00159-2) contains supplementary material, which is available to authorized users.

Evaluating the Association between Enlarged Perivascular Spaces and Disease Worsening in Multiple Sclerosis.

Enlarged perivascular spaces (EPVSs) have been associated with relapses and brain atrophy in multiple sclerosis (MS). We investigated the association of EPVS with clinical and MRI features of disease worsening in a well-characterized cohort of relapsing-remitting MS patients prospectively followed for up to 10 years. Baseline EPVSs were scored on 1.5T MRI in 30 converters to moderate-severe disability, and 30 nonconverters matched for baseline characteristics. EPVS scores were not significantly different between converters and nonconverters, nor associated with accrual of lesions or brain atrophy. Our preliminary findings from a relatively small study sample argue against a potential use of EPVS as early indicator of risk for disease worsening in relapsing-remitting MS patients in a clinical setting. Although the small sample size and clinical 1.5T MRI may have limited our ability to detect a significant effect, we provided estimates of the association of EPVS with clinical and MRI indicators of disease worsening in a well-characterized cohort of MS patients.

Unlike PPARgamma, neither other PPARs nor PGC-1alpha is elevated in the cerebrospinal fluid of patients with multiple sclerosis

Corroborating with prior experimental findings, we recently reported the pronounced elevation of peroxisome proliferator-activated receptor gamma (PPARγ) protein concentration in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), in association with neuroinflammatory markers and clinical severity. Based on subsequent reports on the possible involvement of other PPARs and PPARγ coactivator-1alpha (PGC-1α) in neuroinflammation in MS, we analyzed the protein levels of PPARα, PPARβ/δ, and PGC-1α in a subset of CSF samples from the same cohort of relapsing-remitting MS patients. Unlike PPARγ, none of these proteins were found elevated in MS patients (n=25) compared to non-inflammatory controls (n=16), with the levels of PPARα and PPARβ/δ found generally below the limit of detection, and that of PGC-1α being detectable but comparable in both groups. The clinical and laboratory associations previously reported with PPARγ were however significant even in this smaller subset. The potential underlying causes of these differential alterations are discussed. The findings suggest that despite their proposed involvement in the regulation of inflammatory processes in MS, PPARα, PPARβ/δ, and PGC-1α proteins are not potential biomarkers of neuroinflammation in MS, and indicate a preferential role of PPARγ in the endogenous regulation of autoimmune response in the human CNS within its receptor family.

Relationship between Interferon Beta-1A Administration and Intracranial Vascular Tone Regulation in Patients with Relapsing-Remitting Multiple Sclerosis: A Pilot Study.

Interferon beta (IFN-β) therapy is one of the most commonly prescribed immunomodulatory therapies in relapsing-remitting multiple sclerosis (RRMS). A reversible cerebral vasoconstriction syndrome (RCVS), associated with IFN-β use, has been recently described. For this reason, we tested the effect of once a week intramuscular administration of IFN-β-1A on the function of cerebral vessels in a cohort of RRMS patients. Using transcranial Doppler (TCD) ultrasound, we measured the mean blood flow velocity (MFV) in intracranial vessels 10 h after IFN-β administration. Measurements showed a significant increase in MFV compared to the baseline values in some vessels.

Accounting for disease modifying therapy in models of clinical progression in multiple sclerosis

Identifying predictors of clinical progression in patients with relapsing–remitting multiple sclerosis (RRMS) is complicated in the era of disease modifying therapy (DMT) because patients follow many different DMT regimens. To investigate predictors of progression in a treated RRMS sample, a cohort of RRMS patients was prospectively followed in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB). Enrollment criteria were exposure to either interferon-β (IFN-β, n=164) or glatiramer acetate (GA, n=114) for at least 6months prior to study entry. Baseline demographic and clinical features were used as candidate predictors of longitudinal clinical change on the Expanded Disability Status Scale (EDSS). We compared three approaches to account for DMT effects in statistical modeling. In all approaches, we analyzed all patients together and stratified based on baseline DMT. Model 1 used all available longitudinal EDSS scores, even those after on-study DMT changes. Model 2 used only clinical observations prior to changing DMT. Model 3 used causal statistical models to identify predictors of clinical change. When all patients were considered using Model 1, patients with a motor symptom as the first relapse had significantly larger change in EDSS scores during follow-up (p=0.04); none of the other clinical or demographic variables significantly predicted change. In Models 2 and 3, results were generally unchanged. DMT modeling choice had a modest impact on the variables classified as predictors of EDSS score change. Importantly, however, interpretation of these predictors is dependent upon modeling choice.

Predicting beta-interferon failure in relapsing-remitting multiple sclerosis

Proposed beta-interferon (IFNβ) treatment failure criteria for patients with relapsing-remitting multiple sclerosis (RRMS) have not been validated in clinical practice. This study aimed to establish (a) whether IFNβ attenuated accumulation of fixed disability in comparison to a cohort of matched historical control subjects from the Sylvia Lawry centre for MS research, and (b) whether relapse-based treatment failure criteria or clinical and demographic variables had predictive value for the accumulation of fixed disability. Of the 175 IFNβ-treated RRMS patients, 60 (34%) developed accumulation of fixed disability over a median of five years follow-up, which was significantly less than the rate of accumulation of fixed disability in the control group (P<0.0001). Any relapse in the treatment period predicted accumulation of fixed disability with a sensitivity of 80% and specificity of 43%; patients totally relapse free were less likely to develop accumulation of fixed disability (P <0.002). Multivariate analysis confirmed that a greater risk of accumulation of fixed disability was conferred by a higher Expanded Disability Status Scale (EDSS) score starting IFNβ (P=0.02), and by failure of IFNβ to completely suppress relapses (P=0.004). In conclusion, IFNβ therapy reduced the accumulation of fixed disability in a cohort of RRMS patients, followed for a median of five years. Higher baseline EDSS and failure of complete relapse suppression were associated with a significantly greater likelihood of accumulation of fixed disability. Multiple Sclerosis 2007; 13: 336-342. http://msj.sagepub.com