Faculty Bibliography

BACKGROUND:Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. METHODS:Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID + SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. RESULTS:The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p = 0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p = 0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p = 0.566) and -0.11% (-0.25%, -0.10%; p = 0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p<0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p<0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p = 0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p<0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. CONCLUSIONS:The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics.

BACKGROUND:Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS:We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS:Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS:Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.

Background: Fatigue is among the most frequent and disabling symptoms in RMS patients.
Objective(s): To measure multiple sclerosis (MS) fatigue and its impact on daily life in a real-world population using a survey including the relapsing MS (RMS)-specific Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS).
Method(s): This is an ongoing noninterventional prospective study of RMS patients recruited across the USA via an online survey. Participants completed questionnaires including disease history, disease status, sleep, social and emotional functioning, and the FSIQ-RMS, administered daily for 7 days. The FSIQ-RMS measures self-reported fatigue, and scores range from 0-100 (higher score = greater severity). The impact of fatigue on several aspects of patient's life was rated from 0 (no impact) to 10 (very high impact).
Result(s): A total of 300 RMS participants completed the 7-day assessment: mean age: 43.0 yrs; 88% women; mean diagnosis age: 32 yrs. Fatigue was reported as the symptom with the greatest impact on daily functioning. Participants with lower disability rated fatigue as the most impactful symptom on daily life. Fatigue was rated as severe, with a mean score: 57.3 for the FSIQ-RMS symptom domain; 3 impact sub-domain scores were 42.3, 43.4 and 50.1 (physical, cognitive/emotional, and coping). Fatigue severity did not vary among patients receiving high efficacy disease modifying therapy (DMT) vs other DMTs (44% [n=111] vs 56% [n=143], with score of 57.8?}17.6 vs 55.9?}19.8). Impact of ability to perform daily activities was rated as the highest (6.9/10) in terms of impact on patient's life. Because of MS, 44% of participants did not work. Among those who were working currently (48%), the impact of fatigue on professional life was rated as 4.5/10. Nearly half of the participants (49% of 300) discussed fatigue at each visit with their neurologists and 35% discussed at most visits, with 'impact of fatigue on quality of life' being the most discussed topic (65% of 289). Participants used different approaches to manage their fatigue including avoided heat exposure (77%), took breaks (65%), managed their energy (59%), took non-medicinal products (58%); however, only 6% (of 293) were totally satisfied with these strategies.
Conclusion(s): In this survey including the novel RMS specific FSIQ-RMS, fatigue occurred in most MS participants and adversely influenced patient's daily functioning and life. Fatigue remains a major concern for those with MS

Objective/UNASSIGNED:At the time of multiple sclerosis (MS) diagnosis, identifying those at risk for poorer health-related quality of life and emotional well-being can be a critical consideration for treatment planning. This study aimed to test whether adverse childhood experiences predict MS patients' health-related quality of life and emotional functioning at time of diagnosis and initial course of disease. Methods/UNASSIGNED:We recruited patients at the time of new MS diagnosis to complete self-report surveys at baseline and a one-year follow-up. Questionnaires included the Adverse Childhood Experiences (ACEs), as well as the MS Knowledge Questionnaire (MSKQ), the 36-Item Short Form Health Survey (SF-36), and Self-Management Screening (SeMaS). Results/UNASSIGNED: Conclusions/UNASSIGNED:Childhood adversity predicts health-related quality of life and emotional well-being at time of MS diagnosis and over the initial course of the disease. Measured using a brief screening inventory (ACEs), routine administration may be useful for identifying patients in need of increased supportive services.

OBJECTIVE:To compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BA) and White Americans (WA) and evaluate the role of socioeconomic status. METHODS:We compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit ZIP codes. RESULTS:Of 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs. mild disability, 95% CI 1.18, 1.86) and worse performances on tests of cognitive processing speed (-5.06 fewer correct, CI -5.72, -4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96) and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (-0.77 mL, 95% CI -0.91, -0.64), cortical (-30.63 mL, 95% CI -35.93, -25.33), and deep (-1.58 mL, 95% CI -1.92, -1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BA. CONCLUSION/CONCLUSIONS:We observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors and optimal treatment strategies among BAs with MS is warranted.

Background and aims: Natalizumab extended interval dosing (EID) is associated with lower progressive multifocal leukoencephalopathy risk than standard interval dosing (SID) in anti-JC virus antibody positive multiple sclerosis patients. However, EID efficacy has yet to be demonstrated in a randomised controlled trial, and real-world efficacy data would be valuable. Method(s): This study compared Multiple Sclerosis Performance Test (MSPT) functional changes occurring during treatment with natalizumab EID versus SID in MS PATHS, a network of healthcare institutions providing access to real-world clinical data. An MSPT segment was defined as the time between two MSPT assessments six months apart. MSPT segments with average infusion cycles >35 days and 35 days were defined as EID and SID, respectively. Patients could contribute multiple segments to both groups. Missing covariate data were multiply imputed. Covariates at segment start (Table) were balanced between groups by inverse probability weighting (IPW) based on a logistic propensity score model. Differences in annualized change in MSPT scores were compared between EID/SID arms with weighted linear regression. Result(s): Data from 152 EID and 1,079 SID segments were analysed. After IPW, all baseline factors exhibited a standard mean difference 0.05. Annualised change in MSPT scores of processing speed, manual dexterity, and ambulation did not differ significantly between EID and SID. On average, MSPT scores were maintained or improved while on natalizumab (Figure). Conclusion(s): Functional outcomes between patients treated with natalizumab EID versus SID were comparable. Cognitive processing speed, manual dexterity, and walking speed were maintained or improved over time for both treatment groups

Purpose/UNASSIGNED:Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine. Methods/UNASSIGNED:In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities. Results/UNASSIGNED:Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions. Conclusion/UNASSIGNED:tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.