Comparison of dimethyl fumarate and interferon outcomes in an MS cohort

Abstract Background To compare the effectiveness of dimethyl fumarate (DMF) with subcutaneous interferon beta-1a (IFNβ-1a) in controlling disease activity in patients with relapsing–remitting Multiple Sclerosis (MS). Methods Clinical and imaging data from patients treated with either IFNβ-1a or DMF for at least one year were reviewed. The proportion of patients with at least one clinical relapse within 3–15 months after treatment onset, the proportion of patients with new T2 or gadolinium-enhancing lesions, and the proportion of subjects who achieved no evidence of disease activity (NEDA) status were assessed. Results Three hundred sixteen (98 on IFNβ-1a, 218 on DMF) subjects were included. Baseline demographics were comparable between groups except for age, disease duration, and the number of previous treatments being higher and relapse rate in the prior year being lower in the DMF-treated group. The proportion of patients having a clinical relapse (24.5% vs. 9.6%; OR = 3.04; P < 0.001) or a new MRI lesion (28.6% vs. 8.7%; OR = 4.19, P < 0.001) at 15 months were higher on IFNβ-1a. 79.9% of the patients achieved NEDA status at 15 months on DMF (vs. 51.1% for IFNβ-1a; OR = 0.26, P < 0.001). Further adjustment for demographics, disease characteristics, treatment and relapse history, and subgroup analyses confirmed these findings. Conclusion DMF was associated with less clinical and radiological disease activity compared to IFNβ-1a

Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis

Abstract Background and objectives Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography–angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. Methods PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. Results The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001). Conclusions This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities

Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis

Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p= 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting