Devon S. Conway

Introduction Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are established disease-modifying therapies for relapsing multiple sclerosis (RMS). While DRF has demonstrated improved gastrointestinal tolerability compared to DMF, there is limited research evaluating whether this difference in tolerability translates into a difference in clinical effectiveness. This study evaluated the real-world effectiveness of DRF versus DMF on relapse outcomes in persons with MS (pwMS) in a large US population. Methods This retrospective cohort study utilized the Forian administrative claims database (January 1, 2018–June 30, 2025). Adult pwMS initiating DRF or DMF were identified and propensity score-matched (1:3 ratio) based on baseline demographic and clinical characteristics. Endpoints were assessed over 1- and 2-year follow-up periods. The primary endpoint was annualized relapse rate (ARR). Results The 1-year analysis included 1780 DRF-treated and 5340 DMF-treated pwMS; the 2-year analysis included 739 DRF-treated and 2217 DMF-treated pwMS. At 1 year of treatment, DRF was associated with a significantly lower ARR compared to DMF (0.12 vs. 0.16; p = 0.03), representing a 21% reduction in relapse rate (rate ratio 0.79; 95% CI 0.64–0.97). At 2 years of treatment, DRF maintained a lower ARR compared to DMF (0.11 vs. 0.16; p = 0.02), reflecting a 31% reduction in relapse rate (rate ratio 0.69; 95% CI 0.54–0.87). Conclusion The results of this real-world analysis indicate DRF may be more effective than DMF in reducing relapses over 1 and 2 years of treatment in pwMS.

Background: Relapse prevention in multiple sclerosis (MS) is accomplished with disease-modifying therapy (DMT). Relapse rates typically decrease with age while DMT-associated risks increase, complicating treatment of older persons with MS (PwMS). Objectives: This follow-up study aims to guide treatment decisions by evaluating clinical and patient-reported outcomes among older PwMS who discontinue DMT. Methods: This study included PwMS aged ≥60 evaluated at the Cleveland Clinic from 2010 to 2016, categorized as DMT continuers or discontinuers. Follow-up timeframe was February 2018–April 2024. Outcomes included relapses, magnetic resonance imaging (MRI) activity, and Neuro-QoL and MS Performance Test scores. Mixed-effects regression and survival models were used. Results: In total, 600 PwMS were included. Median follow-up time was 10.5 years (interquartile range 7.7–13.4), 66.0% discontinued DMT, and 3.3% had ≥1 relapse. Relapse risk did not differ significantly between groups (hazard ratio for discontinuers vs. continuers, 1.80, 95% confidence interval 0.51–6.39, p = 0.365). T2 lesions developed in 37.5% of continuers and 36.6% of discontinuers. Gadolinium-enhancing lesions developed in 10.1% and 7.9%, respectively. Neuro-QoL Fatigue T-scores slightly worsened for discontinuers over time. Conclusion: Findings demonstrate low relapse risk among PwMS over age 60, however, MRI changes were common. DMT discontinuation may be considered in this population, though further studies are needed to better understand radiological disease activity.

Introduction Benefit–risk profiles and mode/frequency of administration vary among the four US-approved treatments for anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab+ NMOSD), but no published studies have reported treatment preferences among patients with NMOSD in the USA. Therefore, the objective of this study was to quantify preferences and predict treatment choices among patients with AQP4-Ab+ NMOSD in the USA. Methods A cross-sectional, web-based discrete choice experiment survey was administered to patients with self-reported AQP4-Ab+ NMOSD. Respondents evaluated hypothetical AQP4-Ab+ NMOSD treatment profile pairs defined by efficacy, safety, process-related attributes, and administration mode/frequency. Data were analyzed using a random-parameters logit model to estimate conditional relative importance of attributes, minimum acceptable benefit, and predicted treatment choice in pairwise treatment profile (ravulizumab-like, eculizumab-like, inebilizumab-like, and satralizumab-like) comparisons. Preference heterogeneity was investigated by exploratory subgroup analysis using interaction terms in the regression analysis. Results The 255 survey completers (mean ± standard deviation [SD] age, 41.4 ± 13.7 years) averaged 6.6 ± 5.4 years since diagnosis, and 63.5% identified as female and 46.7% as Black or African American. Rituximab was the most common treatment (34.1% of respondents), and 15.7%, 9.4%, or 7.1% of respondents were receiving eculizumab, inebilizumab, or satralizumab, respectively. Respondents placed greater importance on reducing chance of relapse within the first year of treatment compared with other attributes such as reducing administration frequency from every 2 weeks to every 8 weeks (Q8W); safety attributes (risks of serious opportunistic or recurrent infection, elevated liver enzymes, and meningococcal infection) were rated similar to each other in importance. Pairwise comparisons favored the ravulizumab-like profile (67.8–87.7%) over the other three treatment profiles (12.3–32.2%). Preferences did not vary by age, disease duration, disease impact, or relapses in the past 12 months, but subgroups defined by current treatment type demonstrated different (p = 0.066) preferences. Respondents receiving intravenous/subcutaneous injections alone or with oral immunosuppressive therapy/corticosteroid treatments placed greater importance on reducing chance of relapse versus those receiving oral treatments alone, but they were not more likely to select a Q24W treatment over a Q8W treatment. Conclusions Respondents with AQP4-Ab+ NMOSD placed the highest importance on reducing chance of relapse, placed a high importance on reduced administration frequency, and rated the safety attributes (avoiding treatments with a risk of meningococcal infection, risk of elevated liver enzymes, and risk of other infections) as comparable to each other but less influential than relapse prevention. Respondents were more likely to select a ravulizumab-like profile over comparators. These findings can inform shared decision-making in selecting treatments.

Background: Upper extremity impairment is a common disabling consequence of multiple sclerosis (MS). Little is known about factors influencing upper extremity functioning in MS. Objective: Identify associations with longitudinal changes in upper extremity performance. Methods: Using a real-world, retrospective cohort study (4140 persons with MS and 14,544 observations), multivariable repeated-measures analyses were completed for nine-hole peg test (9HPT) dominant and non-dominant hand times and their difference (asymmetry), with clinical, demographic, and social determinants as covariates. Interactions with time (disease duration) were examined. Results: Cross-sectionally, dominant, and non-dominant hand times were strongly correlated ( ρ = 0.78), and moderately correlated with asymmetry, walking speeds, and depressive symptoms. Longitudinally, older age, males, Hispanics, Blacks, ever smokers, public insurance beneficiaries, greater lower-limb impairment, progressive disease, and greater depressive symptoms were independently associated with worsening dominant and non-dominant times. Public insurance beneficiaries, greater lower-limb impairment, progressive disease, and greater depressive symptoms were associated with greater asymmetry. Males accrued dominant hand dysfunction more rapidly and had greater asymmetry than females over time, while those with increasing lower-limb impairment more rapidly experienced asymmetry over time. Discussion: These findings identify high-risk groups and inform future research to guide strategies for preserving upper extremity function in multiple sclerosis.

Background: Little is known about how multiple sclerosis (MS) presents in Hispanic/Latinx (HL) people with MS (pwMS). Objective: Compare age at onset (AAO) and onset severity between HL versus non-Hispanic White (NHW) pwMS. Methods: A cross-sectional study leveraged the MS PATHS registry spanning seven US tertiary care institutions. HL was subcategorized as HL White (HLW) and HL Other (HLO; all other races). Multivariable models examined relationships between ethnoracial variables and AAO and self-reported presenting disease course. Models were repeated restricting to those born ⩾1970. Results: The study population included 8231 pwMS, including 540 HL (200 HLW, 340 HLO). The sex distribution did not differ across ethnoracial subgroups. From the statistical models (1) HLO pwMS had an earlier AAO and a higher prevalence of initial progressive disease course than NHW pwMS; (2) among all HL pwMS, irrespective of race, AAO did not differ by sex or between relapsing and progressive MS at onset. In younger HLO adults (born ⩾1970), those with progressive MS at onset had an earlier AAO than those with relapsing MS; and (3) in HL pwMS there was no sex-bias in presenting disease course. Discussion: Distinct differences in the presentation of MS in HL compared with NHW individuals were observed.

Background and Purpose: Slowly expanding lesions (SELs) are thought to represent a subset of chronic active lesions and have been associated with clinical disability, severity, and disease progression. The purpose of this study was to characterize SELs using advanced magnetic resonance imaging (MRI) measures related to myelin and neurite density on 7 Tesla (T) MRI.Methods: The study design was retrospective, longitudinal, observational cohort with multiple sclerosis (n = 15). Magnetom 7T scanner was used to acquire magnetization‐prepared 2 rapid acquisition gradient echo and advanced MRI including visualization of short transverse relaxation time component (ViSTa) for myelin, quantitative magnetization transfer (qMT) for myelin, and neurite orientation dispersion density imaging (NODDI). SELs were defined as lesions showing ≥12% of growth over 12 months on serial MRI. Comparisons of quantitative measures in SELs and non‐SELs were performed at baseline and over time. Statistical analyses included two‐sample t‐test, analysis of variance, and mixed‐effects linear model for MRI metrics between lesion types.Results: A total of 1075 lesions were evaluated. Two hundred twenty‐four lesions (21%) were SELs, and 216 (96%) of the SELs were black holes. At baseline, compared to non‐SELs, SELs showed significantly lower ViSTa (1.38 vs. 1.53, p < .001) and qMT (2.47 vs. 2.97, p < .001) but not in NODDI measures (p > .27). Longitudinally, only ViSTa showed a greater loss when comparing SEL and non‐SEL (p = .03).Conclusions: SELs have a lower myelin content relative to non‐SELs without a difference in neurite measures. SELs showed a longitudinal decrease in apparent myelin water fraction reflecting greater tissue injury.