Biogen

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Oral Presentation

FC02.05 - Safety and Efficacy in Patients Treated With Dimethyl Fumarate and Followed For 13 Years: Final Results of ENDORSE

Speakers
Presentation Number
FC02.05
Presentation Topic
Disease Modifying Therapies – Risk Management
Lecture Time
13:48 - 14:00

Abstract

Background

DMF is a well-established therapy for relapsing forms of multiple sclerosis (RMS); data from ENDORSE, an extension to phase 3 studies DEFINE and CONFIRM, has enabled >10 years follow-up.

Objectives

We report safety/efficacy of DMF in patients with RMS treated with DMF and followed for 13 years in ENDORSE (NCT00835770) (2 years DEFINE/CONFIRM, and >10 years ENDORSE).

Methods

Incidence of serious AEs (SAEs), discontinuations due to AEs, annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score were assessed. Patients were treated with DMF 240 mg BID: placebo (PBO)/DMF (PBO, years 0–2 /DMF, years 3–10) or continuously (DMF/DMF). Efficacy outcomes were assessed in patients up to 10 years due to sample size considerations. For lymphocyte analysis, data from first DMF exposure were analysed for patients in DEFINE/CONFIRM/ENDORSE.

Results

At 23 January 2020, 1736 patients enrolled/received ≥1 dose DMF. Of 1736 patients, 760 completed. Patients were followed for a median (min,max) of 6.76(0.04,10.98) years in ENDORSE, and 2 years in DEFINE/CONFIRM. Overall, 551 (32%) patients experienced SAEs; most were MS relapse and fall. There was one case of PML in this study. There was no increased incidence of other infections or serious infections. Sixteen percent (n=282) patients discontinued due to AEs; 2% relapse, 2% disease progression, and 4% GI disorders. ALC decreased over the first 48 weeks, and then remained generally stable for the majority of the study. The proportion of patients with other AEs of special interest (including opportunistic infection, malignancy, and serious herpes zoster) was similar regardless of ALC. For patients continuously treated (n=501), overall ARR remained low (0.141[95% CI, 0.119,0.167]), while for PBO/DMF patients (n=249) ARR decreased after initiating DMF (ARR 0–2 years, 0.330[95% CI, 0.266,0.408]; ARR overall, 0.149[95% CI, 0.116,0.190]). Overall, 60% of DMF/DMF and 66% of PBO/DMF patients remained relapse-free; 20% and 17% of patients had 1 relapse, respectively. Walking abilities were maintained throughout the study; the number of patients with EDSS scores ≤3.5 was 413/479(86%) DMF/DMF (179/217[82%] PBO/DMF) at Year 2, and 173/226(77%) DMF/DMF (67/90[74%] PBO/DMF) at Year 10. Seventy-two percent and 73% of DMF/DMF and PBO/DMF patients, respectively, had no 24-week confirmed disability progression over 10 years.

Conclusions

These safety and efficacy data in patients followed for 13 years, support DMF as a long-term option for patients with RMS.

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Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Poster Presentation

P0386 - Safety and Effectiveness of Dimethyl Fumarate Maintained Over 5 Years in Multiple Sclerosis Patients Treated in Routine Medical Practice (ID 430)

Speakers
Presentation Number
P0386
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

In clinical studies, delayed-release dimethyl fumarate (DMF) demonstrated a favorable benefit–risk profile in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies enable characterization of risks that may only emerge with long-term exposure in clinical practice. ESTEEM (NCT02047097) is an ongoing 5-year study characterizing long-term safety and effectiveness of routinely prescribed DMF in MS patients.

Objectives

To report 5-year safety and effectiveness in patients with multiple sclerosis (MS) treated with DMF under routine care.

Methods

Patients treated with DMF were recruited from ~380 sites. The primary objective was to determine incidence, type, and pattern of serious adverse events (SAEs), and AEs leading to discontinuation. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs).

Results

On April 3, 2019, 5084 patients had ≥1 dose of DMF and qualified for analysis. Mean (SD) age was 40.0 (11.2) years at enrollment, and 74% were female. In total, 1506 patients were treated for >24–48 months, and 441 were treated for >48 months. Two hundred and forty-five patients (4.8%) experienced SAEs; infections (n=64; 1.3%) and nervous system disorders (n=35; <1%) were most common. There were 1676 (33.0%) permanent treatment discontinuations: 965 (19.0%) due to AEs (most commonly: gastrointestinal AEs [395, 7.8%] and occurrence of lymphopenia [125, 2.5%]) and 260 (5.1%) due to insufficient efficacy. Overall ARR over the period of up to 5 years (0.09; 95% CI: 0.09–0.10) was significantly lower than in the year prior to baseline (0.82, 95% CI: 0.80–0.84), representing an 88.6% risk reduction [95% CI: 87.7–89.4 P<0.0001]). At 54 months, the Kaplan-Meier estimated probability of patients without relapse was 71.1% (n=4286). PROs were generally stable from baseline to Year 5.

Conclusions

Results from the ongoing study with up to 5 years follow-up reveal no new safety concerns emerging from real-world use of DMF. DMF demonstrated beneficial therapeutic effects for those patients that remained on treatment up to 5 years.

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