Washington University School in St. Louis
Division of Biostatistics

Author Of 4 Presentations

Clinical Outcome Measures Poster Presentation

P0021 - A propensity-matched comparison of long-term disability progression in MS patients treated with dimethyl fumarate or fingolimod (ID 709)

Speakers
Presentation Number
P0021
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Previous comparative effectiveness studies in multiple sclerosis (MS) have shown similar efficacy between dimethyl fumarate (DMF) and fingolimod (FTY) on measures of inflammatory disease activity but most studies did not assess long-term disability.

Objectives

To compare long-term disability progression over 5 years (yrs), as assessed by Patient-Determined Disease Steps (PDDS), in NARCOMS registry participants (pts) treated with DMF or FTY.

Methods

The NARCOMS registry is a voluntary self-report registry of people with MS. Pts provide health-related information at enrollment and every 6 months thereafter. We identified pts with RRMS; living in the US; and initiating index DMT (DMF or FTY) from Spring 2011 through Spring 2018. Pts were included if they had ≥1 yr follow-up on index DMT. DMF pts treated with prior FTY, and FTY pts treated with prior DMF, were excluded. We used 1:1 propensity-score matching (PSM) to match FTY to DMF pts. Baseline factors (at time of index DMT initiation) used for PSM were age, disease duration, sex, number of prior DMTs, education, PDDS, cognition score, depression score, relapses in last 6 months, and cardiovascular comorbidities. Time to 6-month confirmed disability progression (≥1-point increase on PDDS sustained for ≥6 months) was estimated using the Kaplan-Meier method and compared using a Cox proportional hazards regression model with robust sandwich estimators. Pts were censored at last follow-up or at the time of DMT discontinuation.

Results

Overall, 689 DMF and 565 FTY pts were included. After PSM, 468 DMF pts were matched with 468 FTY pts. The survey compliance was high in both groups, with >93% of pts in both groups completing ≥50% of surveys while on treatment. Baseline characteristics were well-balanced after PSM, with standardized differences <0.1 for each covariate. Median treatment duration was 3.0 yrs for DMF and 4.0 yrs for FTY. At 5 yrs, 68.3% (95% CI: 62.4-73.5) of DMF pts and 63.3% (95% CI: 59.6-70.1) of FTY pts were free from 6-month confirmed PDDS progression (hazard ratio: 1.01 [95% CI: 0.79-1.28]; p=0.95).

Conclusions

In this propensity-matched analysis of MS pts from the NARCOMS registry, there was no significant difference between DMF and FTY on confirmed disability (PDDS) progression over 5 yrs. These results are consistent with previous studies that have shown similar effectiveness between DMF and FTY on relapse and MRI outcomes.

Supported by: Biogen; NARCOMS is a project of the CMSC

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Clinical Outcome Measures Poster Presentation

P0068 - Disability Progression in MS Participants Treated with Delayed-release Dimethyl Fumarate: Age-related Subgroup Analysis of the NARCOMS Registry (ID 397)

Speakers
Presentation Number
P0068
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Dimethyl fumarate (DMF) clinical trials excluded relapsing-remitting multiple sclerosis (RRMS) patients aged >55 years (yrs). The limited data on DMF use in this age group evaluated relapses but not disability. Unlike relapses, which often decrease as MS patients age, disability progression often increases.

Objectives

To characterize long-term disability outcomes over 4.5 yrs of DMF treatment in RRMS participants based on age at time of DMF initiation.

Methods

We identified NARCOMS participants (pts) with RRMS, living in the US, and initiating DMF from Fall 2013–Spring 2018 with ≥1 yr follow-up. We dichotomized age at DMF initiation as <55 (younger) and ≥55 yrs (older). Disability was measured using the Patient Determined Disease Steps (PDDS). Time to 6-month confirmed PDDS progression (≥1-point increase) and conversion to SPMS were estimated using the Kaplan-Meier method and compared using a log rank test. Cox proportional hazards regression models were adjusted for sex and initial PDDS level. Pts were censored at last follow-up or DMF discontinuation, whichever came first. Safety data were not collected.

Results

647 RRMS pts initiated DMF. In the younger subgroup (n=351, 54%), median age was 47 yrs, 88% female, and 24% reported a relapse in the last 6 months. In the older subgroup (n=296, 46%), median age was 60 yrs, 82% female, and 22% reported a relapse in the last 6 months. Compared to the younger subgroup, older pts had longer MS disease duration (11 vs 17 yrs, p<0.001) and significantly greater disability at baseline as measured by PDDS. Median treatment duration was 2.5 yrs in younger pts and 2 yrs in older pts. At last follow-up, 283 (81%) younger pts and 236 (80%) older pts remained on DMF. Most pts in both groups were estimated to remain free of disability progression over 4.5 yrs: 64% (95%CI: 57-71) of younger pts vs 74% (95%CI: 67-80) of older pts (p=0.12). Most pts in both subgroups also were estimated to remain free from conversion to SPMS over 4.5 yrs: 90% (95%CI: 85-94) of younger pts vs 86% (95%CI: 79-91) of older pts (p=0.17).

Conclusions

Conclusions: As expected, older pts (≥55 yrs) had significantly longer MS disease duration and higher baseline disability compared with younger pts (<55 yrs). Despite these baseline differences, most pts in both groups remained free of PDDS progression and free from conversion to SPMS over 4.5 yrs of DMF treatment.

Supported by: Biogen; NARCOMS is a project of the CMSC

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Imaging Poster Presentation

P0581 - Gradient echo magnetic resonance imaging to detect central vein sign in patients with Multiple Sclerosis (ID 1528)

Speakers
Presentation Number
P0581
Presentation Topic
Imaging

Abstract

Background

Diagnostic criteria for multiple sclerosis (MS) have undergone several iterations in the past 20 years, resulting in increased sensitivity and earlier diagnosis, but also increased misdiagnoses due to reduced specificity. Biomarkers are needed to distinguish MS from its mimics and between MS subtypes. MS lesions in white matter (WM) typically form around a central vein, which can be visualized with FLAIR* imaging (Sati, et al, 2012). Central vein sign (CVS) presence on MRI can help differentiate MS from other diseases with WM T2-weighted hyperintensities and may increase the sensitivity and specificity of MS diagnosis.

Objectives

To apply MRI-based gradient echo plural contrast imaging (GEPCI) approach (Luo, et al, 2012) to generate FLAIR*-like images and detect CVS in patients with progressive MS (PMS) and relapsing remitting MS (RRMS). To quantitatively evaluate tissue damage in lesions with and without CVS using tissue-specific GEPCI R2t* metric (Xiang, et al, 2019).

Methods

MRI scans of PMS (n=39) and RRMS subjects (n=30) were analyzed for the CVS within WM lesions. Presence of CVS, lesion volume, and anatomic location were determined. To quantitatively evaluate the severity of brain-tissue damage in MS lesions, mean R2t* was calculated. R2t* is a quantitative measure that correlates with brain tissue cellular density and is decreased in areas of reduced tissue integrity. The proportion of total lesions with CVS was calculated, excluding confluent lesions and lesions with more than 1 central vein. Median proportions in PMS and RRMS subjects were compared using the Wilcoxon sign rank test. Individual lesion CVS status was examined using generalized linear models. Linear mixed models adjusted for age were used to evaluate predictors of mean R2t* in nonconfluent lesions with only one central vein of sufficient size. Associations of CVS and clinical data from time of MRI scan, including Expanded Disability Status Scale (EDSS), symbol digit modality test (SDMT), and multiple sclerosis functional composite (MSFC) were made using Spearman correlations.

Results

The PMS group had significantly higher EDSS scores and poorer performance on SDMT and MSFC than the RRMS group. There were no significant differences in total CVS and percentage of CVS per lesion between MS subtypes. Controlling for age, EDSS, and lesion volume did not increase the odds of either group having CVS. Lesions with CVS had lower R2t* (greater tissue damage). However, accounting for MS type, age, and lesion count reduced significance (p = 0.09). Mean R2t* was significantly lower in PMS than RRMS (p = 0.027) and declined with age (p = 0.023).

Conclusions

This study did not find that the presence of CVS could distinguish between patients with RRMS and PMS. Our data suggest that lesions with CVS have more tissue damage. Due to reduced significance after accounting for additional variables, further studies with more patients are needed.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1009 - Characteristics and patient-reported outcomes of patients initiating ocrelizumab in the NARCOMS Registry from 2017 to 2019 (ID 1221)

Speakers
Presentation Number
P1009
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Ocrelizumab (OCR) was approved for relapsing and primary progressive forms of multiple sclerosis (MS) in 2017. Patient-reported outcome data among patients initiating OCR in clinical practice is limited.

Objectives

To evaluate the characteristics, experience and outcomes of participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry who initiated OCR.

Methods

NARCOMS is a voluntary registry enrolling persons with MS who update their information using semi-annual surveys. This analysis included participants initiating OCR between April 2017 and April 2019, including a subset of participants who completed 1-year follow-ups. Outcomes included Patient Determined Disease Steps (PDDS), relapses, health care utilization and employment (i.e. employed/unemployed status, absenteeism). Changes from baseline for the subgroup who completed 1-year surveys were evaluated using the nonparametric Wilcoxon-Signed Rank or McNemar’s tests.

Results

During the study period 829 participants initiated OCR. They had a mean [SD] age of 56.6 [10.6] years and time since diagnosis of 18.7 [9.9] years. Most participants were female (75.3%). The most common clinical course was relapsing-remitting (45.4%) followed by secondary progressive (32.1%) and primary progressive (22.6%). The median (interquartile range [IQR]) PDDS was 5.0 [3.0–6.0]. Similar baseline characteristics were observed in the subgroup of 435 participants who had ≥1 year of follow-up (median [IQR] follow-up, 1.5 [1.0–2.0] years). In this subgroup, participants were less likely to report a steroid-treated relapse at 1 year (7.7%) compared with baseline (1-year lookback, 4.7%; p=0.04), although no differences were observed with respect to emergency room or hospital admissions. More than half of participants reported either improvement (40.7%) or no change (15.3%) on the PDDS; 44% reported worsening. Among employed participants at baseline (n=139), 8% reported leaving the workforce during follow-up; among those who remained employed, fewer reported missing work in the follow-up year (33.9%) compared with baseline (1-year lookback; 46.5%; p=0.003).

Conclusions

Participants initiating ocrelizumab in the NARCOMS registry are representative of a prevalent MS population, consistent with the full registry population. Patients with longitudinal follow-up on ocrelizumab reported fewer relapses and lower work absenteeism, with no differences in health resource utilization compared to baseline.

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