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

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

Background

Diroximel fumarate (DRF) is an oral fumarate recently approved in the United States for relapsing forms of multiple sclerosis (MS). DRF demonstrated favorable gastrointestinal (GI) tolerability in clinical studies of MS patients (pts). Discontinuations due to GI adverse events (AEs) were low (0.7%) in an open-label 2-year study. In a randomized study versus dimethyl fumarate (DMF), fewer pts reported GI AEs (35%, 88/253 DRF vs 49%,123/251 DMF) and GI AEs leading to discontinuation (0.8% DRF vs. 4.8% DMF); GI AEs were less frequently reported as moderate/severe for DRF (23%, 20/88) vs DMF (40%, 49/123). It is important to characterize DRF persistence in a real-world setting and effectiveness across different patient types and geographies.

Objectives

To describe the novel design of the DRF EXPERIENCE (EXPloring diroximEl fumarate Real-world experIENCE) Study Initiative.

Methods

A Phase IV DRF study should collect data on meaningful real-world outcomes, including treatment persistence, real-world tolerability, and clinical effectiveness, including cognitive changes, to align with evolving treatment goals. As DRF was designed to reduce treatment burden, impact on quality of life should also be assessed. Country-specific nuances due to unique healthcare environments, ethnicity, and cultural considerations diminish the utility of a single-study design.

Results

The DRF EXPERIENCE Study Initiative uses a novel design comprising 4 individual studies, each conducted in different regions but anchored by a core protocol to characterize the early experience in pts initiating DRF per routine care. The core protocol defines a set of required assessments for each study, but also allows flexibility to include others that address country-specific research questions. The primary objective is to characterize persistence to DRF at 1 year. Core protocol assessments include relapse, disability, cognitive changes, and pt-reported Neuro-QoL. Each study will enroll ~200 pts; the pooled total sample size of ~800 will improve ability for subgroup analyses. Pts will be followed for 2 years and include those newly initiating a disease modifying therapy (DMT) or switching from previous DMTs (including prior DMF).

Conclusions

The DRF EXPERIENCE Study Initiative uses a novel design to characterize the improved GI tolerability profile and effectiveness of DRF in MS pts in the real-world and will be informative to providers and patients when considering MS treatment goals together with the burden of therapy.

Supported by: Biogen

Background

Diroximel fumarate (DRF) is an oral fumarate recently approved in the United States for relapsing forms of multiple sclerosis (MS). DRF demonstrated favorable gastrointestinal (GI) tolerability in clinical studies of MS patients (pts). Discontinuations due to GI adverse events (AEs) were low (0.7%) in an open-label 2-year study. In a randomized study versus dimethyl fumarate (DMF), fewer pts reported GI AEs (35%, 88/253 DRF vs 49%,123/251 DMF) and GI AEs leading to discontinuation (0.8% DRF vs. 4.8% DMF); GI AEs were less frequently reported as moderate/severe for DRF (23%, 20/88) vs DMF (40%, 49/123). It is important to characterize DRF persistence in a real-world setting and effectiveness across different patient types and geographies.

Objectives

To describe the novel design of the DRF EXPERIENCE (EXPloring diroximEl fumarate Real-world experIENCE) Study Initiative.

Methods

A Phase IV DRF study should collect data on meaningful real-world outcomes, including treatment persistence, real-world tolerability, and clinical effectiveness, including cognitive changes, to align with evolving treatment goals. As DRF was designed to reduce treatment burden, impact on quality of life should also be assessed. Country-specific nuances due to unique healthcare environments, ethnicity, and cultural considerations diminish the utility of a single-study design.

Results

The DRF EXPERIENCE Study Initiative uses a novel design comprising 4 individual studies, each conducted in different regions but anchored by a core protocol to characterize the early experience in pts initiating DRF per routine care. The core protocol defines a set of required assessments for each study, but also allows flexibility to include others that address country-specific research questions. The primary objective is to characterize persistence to DRF at 1 year. Core protocol assessments include relapse, disability, cognitive changes, and pt-reported Neuro-QoL. Each study will enroll ~200 pts; the pooled total sample size of ~800 will improve ability for subgroup analyses. Pts will be followed for 2 years and include those newly initiating a disease modifying therapy (DMT) or switching from previous DMTs (including prior DMF).

Conclusions

The DRF EXPERIENCE Study Initiative uses a novel design to characterize the improved GI tolerability profile and effectiveness of DRF in MS pts in the real-world and will be informative to providers and patients when considering MS treatment goals together with the burden of therapy.

Supported by: Biogen