Relationship between lymphopenia and disease activity in persons with multiple sclerosis treated with dimethyl fumarate.

BACKGROUND: Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). Its precise mechanism in treating MS involves nuclear factor erythroid-derived 2-related factor-dependent and -independent pathways. Lymphopenia, defined according to NIH Common Terminology for Adverse Events v5.0, is one potential adverse effect. It is unclear whether lymphopenia correlates with disease activity; existing studies have yielded conflicting results. OBJECTIVE: To determine whether lymphopenia in DMF-treated persons with MS (PwMS) correlates with disease activity. METHODS: A retrospective chart review of 66 PwMS treated with DMF between January 1, 2013 and September 30, 2020. RESULTS: Participants who experienced lymphopenia were older (p < 0.001), and had a longer disease duration (p = 0.012) and lower baseline absolute lymphocyte count (ALC) (p < 0.001). Breakthrough disease activity was the most common reason for DMF discontinuation (53.0%). Lymphopenia occurred in 36.4%, with ALCs decreasing over the first 12 months of therapy before plateauing. Lymphopenia was associated with a trend towards reduced relapses (p = 0.059) and significantly improved MRI activity (p = 0.001) and no evidence of disease activity (NEDA-3) (p = 0.022), but not disability progression (p = 0.549). Persons with lymphopenia were significantly less likely to be treated with another DMT after DMF (p = 0.036). CONCLUSION: Risk factors for and rates of lymphopenia resembled existing data. Lymphopenia was associated with significantly improved MRI activity and achievement of NEDA-3, and whether PwMS were treated with another DMT after DMF. Further studies are required to clarify the mechanism of DMF, lymphocyte subsets and their relationship with disease activity, and which characteristics predict response to DMF.

Potential of Timed 25-Foot Walk Values in Predicting Maximum Walking Distance in Persons with Multiple Sclerosis.

BACKGROUND: Expanded Disability Status Scale (EDSS) scores of 4.0 or greater are determined primarily by maximum walking distance (MWD). Estimation of MWD by persons with multiple sclerosis (MS) is often used due to the impracticality of formally walking a person with MS in a clinic setting. Previous studies have demonstrated discrepancies between estimated and actual MWDs. Whether Timed 25-Foot Walk test (T25FW) values can be used to predict MWD is currently unknown. This study aimed to determine whether T25FW time is predictive of MWD in persons with MS. METHODS: This study is a post hoc analysis of a previously described prospective cohort study. Persons with MS with an EDSS score of 3.5 to 5.5 were included. The participant's T25FW values and MWD were measured. RESULTS: Of the 38 adult participants (mean age, 50.8 years; 27 women [71%]), 24 (63%) had relapsing-remitting MS. The median EDSS score was 4.5 (range, 3.5-5.5). The T25FW times were divided into seven categories (<5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10.0 seconds). The MWDs were divided into corresponding EDSS score categories: ≥500, 300-499, 200-299, 100-199, and ≤99 m. Ordinal logistic regression, when controlled for age, found the T25FW categories to be predictive of EDSS score (χ2 = 17.630, df = 7, P = .014). CONCLUSIONS: The T25FW value may be used as a surrogate estimate of MWD. Further studies are needed to confirm the reliability of the T25FW in predicting MWD.

Self-reported maximum walking distance in persons with MS may affect the EDSS.

BACKGROUND: In persons with MS (PwMS), the Expanded Disability Status Scale (EDSS) is used to monitor disability progression. Scores between 4.0 and 7.0 are determined by maximum walking distance. Self-estimation of this value is often employed in clinic settings. OBJECTIVE: To examine the accuracy with which PwMS estimate their walking distance, and observe subsequent changes to the EDSS. METHODS: This prospective cohort study recruited PwMS with previously recorded EDSS of 3.5-7.0. Participants estimated their maximum walking distance and then walked as far as they could along a pre-specified course. Each distance was converted to an EDSS score, the "estimated EDSS" and the "actual EDSS". Chi-Square analysis was used to compare EDSS scores. Logistic regression was used to determine predictors of inaccurate estimations. RESULTS: Of the 66 PwMS in this study, 43.9% had a difference in the actual EDSS compared to the estimated EDSS. Median estimated EDSS was 4.75 (range 3.0-7.0); after walking assessment, median actual EDSS was 5.0 (range 3.0-7.0), which represented a significant difference [X2 (df 64, N=66)=206.9; p<0.001]. Actual EDSS decreased in 9 PwMS (13.6%) and increased in 20 PwMS (30.3%). Logistic regression did not find any demographic/disease characteristic to be predictive of this discrepancy. CONCLUSION: Some PwMS do not accurately estimate maximum walking distance; only 56.1% of PwMS accurately estimated their actual EDSS.