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Cognitive deterioration is common in multiple sclerosis (MS) and requires regular follow-up. Currently, cognitive status is measured in clinical practice using paper-and-pencil tests, which are both time-consuming and costly. Remote monitoring of cognitive status could offer a solution because previous studies on telemedicine tools have proved its feasibility and acceptance among people with MS. However, existing smartphone-based apps include designs that are prone to motor interference and focus primarily on information processing speed, although memory is also commonly affected. This study aims to validate a smartphone-based cognitive screening battery, icognition, to detect deterioration in both memory and information processing speed. The icognition screening battery consists of 3 tests: the Symbol Test for information processing speed, the Dot Test for visuospatial short-term memory and learning, and the visual Backward Digit Span (vBDS) for working memory. These tests are based on validated paper-and-pencil tests: the Symbol Digit Modalities Test, the 10/36 Spatial Recall Test, and the auditory Backward Digit Span, respectively. To establish the validity of icognition, 101 people with MS and 82 healthy participants completed all tests. Of the 82 healthy participants, 20 (24%) repeated testing 2 to 3 weeks later. For each icognition test, validity was established by the correlation with its paper-and-pencil equivalent (concurrent validity), the correlation and intraclass correlation coefficient (ICC) between baseline and follow-up testing (test-retest reliability), the difference between people with MS and healthy participants, and the correlation with other clinical parameters such as the Expanded Disability Status Scale. All icognition tests correlated well with their paper-and-pencil equivalents (Symbol Test: r=0.67; P<.001; Dot Test: r=0.31; P=.002; vBDS: r=0.69; P<.001), negatively correlated with the Expanded Disability Status Scale (Symbol Test: ρ=-0.34; P<.001; Dot Test: ρ=-0.32; P=.003; vBDS: ρ=-0.21; P=.04), and showed moderate test-retest reliability (Symbol Test: ICC=0.74; r=0.85; P<.001; Dot Test: ICC=0.71; r=0.74; P<.001; vBDS: ICC=0.72; r=0.83; P<.001). Test performance was comparable between people with MS and healthy participants for all cognitive tests, both in icognition (Symbol Test: U=4431; P=.42; Dot Test: U=3516; P=.32; vBDS: U=3708; P=.27) and the gold standard paper-and-pencil tests (Symbol Digit Modalities Test: U=4060.5, P=.82; 10/36 Spatial Recall Test: U=3934; P=.74; auditory Backward Digit Span: U=3824.5, P=.37). icognition is a valid tool to remotely screen cognitive performance in people with MS. It is planned to be included in a digital health platform that includes volumetric brain analysis and patient-reported outcome measures. Future research should establish the usability and psychometric properties of icognition in a remote setting.

In multiple sclerosis (MS), the early detection of disease activity or progression is key to inform treatment changes and could be supported by digital tools. We present a novel CE-marked and FDA-cleared digital care management platform consisting of (1) a patient phone/web application and healthcare professional portal (icompanion) including validated symptom, disability, cognition, and fatigue patient-reported outcomes; and (2) clinical brain magnetic resonance imaging (MRI) quantifications (icobrain ms). We validate both tools using their ability to detect (sub)clinical disease activity (known-groups validity) and real-world data insights. Surveys showed that 95.6% of people with MS (PwMS) were interested in using an MS app, and 98.2% were interested in knowing about MRI changes. The icompanion measures of disability (p < 0.001) and symptoms (p = 0.005) and icobrain ms MRI parameters were sensitive to (sub)clinical differences between MS subtypes. icobrain ms also decreased intra- and inter-rater lesion count variability and increased sensitivity for detecting disease activity/progression from 24% to 76% compared to standard radiological reading. This evidence shows PwMS’ interest, the digital care platform’s potential to improve the detection of (sub)clinical disease activity and care management, and the feasibility of linking different digital tools into one overarching MS care pathway.

ObjectivesSome disease-modifying therapies (DMTs) have been associated with COVID-19 severity in people with MS. Comprehensive exploration of these relationships in large international samples is needed.MethodsClinician-reported demographic/clinical data from 27 countries were aggregated into a dataset of 5,648 patients with suspected/confirmed COVID-19. COVID-19 severity outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, death) assessed using multilevel mixed-effect ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were compared to glatiramer acetate, dimethyl fumarate, pooled other DMTs, and natalizumab.ResultsOf 5,648 patients (83.4% confirmed COVID-19) were included. Compared to glatiramer acetate, ocrelizumab and rituximab were associated with higher probability of hospitalisation (4%(95%CI=1–7) & 7%(95%CI=4–11)), ICU/artificial ventilation (2%(95%CI=0–4) & 4%(95%CI=2–6)), and death (1%(95%CI=0–2) & 2%(95%CI=1–4)) [predicted marginal effects]. Untreated patients had 5%(95%CI=2–8), 3%(95%CI=1–5), and 1%(95%CI=0–3) higher probabilities of the three respective levels of COVID-19 severity than glatiramer acetate. Compared to pooled other DMTs and to natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. Evaluation of interferon associations with COVID-19 severity found these only apparent in comparison with the untreated but not vs individual or pooled other DMTs. All associations persisted/enhanced on restriction to confirmed COVID-19.ConclusionsAnalysing the largest international real-world dataset of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab) are associated with more severe course of COVID-19, while interferon-based DMTs have no intrinsic protective benefit from other treatment.