Faculty Bibliography

OBJECTIVE: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis. METHODS: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted. RESULTS: In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (beta = 0.16, p < 0.001). Relapses of all phenotypes promoted disability accumulation, with the most pronounced increase associated with pyramidal (beta = 0.27 (0.25-0.29)), cerebellar (beta = 0.35 (0.30-0.39)) and bowel/bladder (beta = 0.42 (0.35-0.49)) phenotypes (mean (95% confidence interval)). Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain, as well as anatomically related domains. CONCLUSION: Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.

BACKGROUND: Dimethyl fumarate (DMF) was approved by the US Food and Drug Administration (FDA) for treatment of relapsing-remitting multiple sclerosis (RRMS) based on two phase III randomized clinical trials (RCTs). There were not enough non-White patients enrolled in these RCTs to allow for subgroup analysis based on race. Efficacy and tolerability of DMF therapy across various racial groups is unknown. METHODS: Retrospective chart review was performed on all patients with RRMS who were started on DMF in two tertiary multiple sclerosis (MS) clinics. Efficacy and tolerability of DMF was compared across three self-identified racial groups: White-American (WA), African-American (AA) and Hispanic-American (HA). RESULTS: A total of 390 RRMS patients were included in the study: 261 (66.9%) WA, 69 (17.7%) AA and 52 (13.3%) HA. When comparing 'pre-DMF' (1 year) and 'on DMF' (mean follow up of 14 months) periods, statistically significant reduction in rates of annualized relapses (WA from 0.44 to 0.19, AA from 0.39 to 0.15, and HA from 0.39 to 0.14; no differences between groups), new T2 lesions (WA from 45% to 23%, AA from 39% to 23%, HA from 52% to 26%; no difference between groups), and Gd+ lesions (WA from 25% to 13%, AA from 24% to 7%, HA from 23% to 12%; no difference between groups) were seen. DMF was relatively well tolerated across all groups, with an overall discontinuation rate of 20% (no difference between the three groups). CONCLUSION: Efficacy of DMF in our clinic population did not differ across three major ethnic groups, WA, AA and HA, and was comparable with results observed in the pivotal studies. These 'real-life' data suggest that race is not a factor that needs to be taken into account when initiating DMF.

The rapid escalation in prices of disease-modifying therapies (DMTs) for multiple sclerosis (MS) over the past decade has resulted in a dramatic overall increase in the costs of MS-related care. In this article, we outline various approaches whereby neurologists can contribute to responsible cost containment while maintaining, and even enhancing, the quality of MS care. The premise of the article is that clinicians are uniquely positioned to introduce innovative management strategies that are both medically sound and cost-efficient. We describe our "top 5" recommendations, including strategies for customizing relapse treatment; developing alternative dosing schedules for Food and Drug Administration-approved MS DMTs; using off-label therapies for relapse suppression; and limiting the use of DMTs to those who clearly fulfill diagnostic criteria, and who might benefit from continued use over time. These suggestions are well-grounded in the literature and our personal experience, but are not always supported with rigorous Class I evidence as yet. We advocate for neurologists to take a greater role in shaping clinical research agendas and helping to establish cost-effective approaches on a firm empiric basis.

BACKGROUND: Discontinuation of injectable disease-modifying therapy (DMT) for multiple sclerosis (MS) after a long period of relapse freedom is frequently considered, but data on post-cessation disease course are lacking. OBJECTIVES: (1) To compare time to first relapse and disability progression among 'DMT stoppers' and propensity-score matched 'DMT stayers' in the MSBase Registry; (2) To identify predictors of time to first relapse and disability progression in DMT stoppers. METHODS: Inclusion criteria for DMT stoppers were: age >/=18 years; no relapses for >/=5 years at DMT discontinuation; follow-up for >/=3 years after stopping DMT; not restarting DMT for >/=3 months after discontinuation. DMT stayers were required to have no relapses for >/=5 years at baseline, and were propensity-score matched to stoppers for age, sex, disability (Expanded Disability Status Score), disease duration and time on treatment. Relapse and disability progression events in matched stoppers and stayers were compared using a marginal Cox model. Predictors of first relapse and disability progression among DMT stoppers were investigated using a Cox proportional hazards model. RESULTS: Time to first relapse among 485 DMT stoppers and 854 stayers was similar (adjusted HR, aHR=1.07, 95% CI 0.84 to 1.37; p=0.584), while time to confirmed disability progression was significantly shorter among DMT stoppers than stayers (aHR=1.47, 95% CI 1.18 to 1.84, p=0.001). The difference in hazards of progression was due mainly to patients who had not experienced disability progression in the prebaseline treatment period. CONCLUSIONS: Patients with MS who discontinued injectable DMT after a long period of relapse freedom had a similar relapse rate as propensity score-matched patients who continued on DMT, but higher hazard for disability progression.