University of Leipzig
Department of Neurology

Author Of 3 Presentations

Clinical Trials Poster Presentation

P0200 - Diroximel Fumarate in Patients With Relapsing-Remitting Multiple Sclerosis: Interim Safety and Efficacy Results From the Phase 3 EVOLVE-MS-1 Study (ID 435)

Speakers
Presentation Number
P0200
Presentation Topic
Clinical Trials

Abstract

Background

Diroximel fumarate (DRF) is a novel oral fumarate for relapsing forms of multiple sclerosis (MS). DRF is converted to monomethyl fumarate (MMF), the same pharmacologically active metabolite as dimethyl fumarate (DMF). Oral administration of DRF 462mg and DMF 240mg produce bioequivalent MMF exposure and are therefore expected to exhibit comparable efficacy and safety profiles. DRF has an improved gastrointestinal (GI) tolerability profile compared to DMF.

Objectives

To report interim safety, tolerability, and efficacy outcomes in DRF-treated patients from EVOLVE-MS-1 and to assess GI tolerability in a subgroup of patients who received DMF prior to DRF.

Methods

EVOLVE-MS-1 (NCT02634307) is an ongoing, open-label, 96-week study assessing DRF safety, tolerability, and efficacy in adults with relapsing-remitting MS. Patients entered the study either as newly enrolled in the DRF clinical development program or after completing EVOLVE-MS-2 (NCT03093324), a randomized, blinded, phase 3 study in which patients received DRF or DMF over 5 weeks.

Results

As of 2 July 2019, 1051 patients were enrolled, 458 of whom had completed EVOLVE-MS-2. Median DRF exposure was 1.5 (range 0.0-1.9) years. Overall, 44.2% of patients completed the study and 17.3% discontinued treatment; 6.3% discontinued due to AEs and 0.7% due to GI AEs. AEs occurred in 82.1% (863/1051) of patients; 90% (779/863) were mild or moderate in severity. Incidence of GI AEs was 28.4% (299/1051) in the overall population, 21.7% (51/235) in patients with prior DRF treatment, and 21.5% (48/223) in patients with prior DMF treatment. Patients who had experienced GI AEs in EVOLVE-MS-2 (DRF to DRF, 33.6% [79/235]; DMF to DRF, 44.8% [100/223]) had low rates of recurrence (3.4% [8/235] and 3.6% [8/223] for those previously treated with DRF and DMF, respectively) and/or onset of new GI AEs (19.6% [46/235] and 20.6% [46/223], respectively) in EVOLVE-MS-1, regardless of prior treatment group. In the overall population (n=1051), annualized relapse rate was 0.14, and 86.1% of patients were relapse-free. Outcomes in patients who were newly diagnosed or most recently switched from interferon or glatiramer acetate will be presented.

Conclusions

Safety and efficacy results from the ongoing EVOLVE-MS-1 study were consistent with previous findings of DRF and the known benefit-risk profile for DMF. In patients who switched from DMF to DRF, no worsening of tolerability was observed.

Supported by: Biogen

Collapse
Diagnostic Criteria and Differential Diagnosis Poster Presentation

P0263 - Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis (ID 1336)

Abstract

Background

Up to date prognostic estimation in newly diagnosed patients is hardly possible while the differentiation between disabling versus more benign courses is of utmost relevance. Reliable blood-based biomarkers that are associated with diagnosis and prognosis of multiple sclerosis (MS) have not been established.

Objectives

Can serum neurofilament light chain measurements serve as a reliable biomarker for diagnostic accuracy and prognosis for multiple sclerosis patients at the time point of diagnosis?

Methods

In a multicenter prospective longitudinal observational cohort, patients with a first diagnosis of multiple sclerosis (MS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers and assessed yearly with a standardized protocol. Patients were offered standard immunotherapies according to national treatment guidelines. Serum NfL concentrations were measured using an ultrasensitive single-molecule array (Simoa).

Results

A possible association between sNfL levels and clinical diagnosis, relapses, MRI parameters and treatment decisions was tested in 814 patients classified according to current (2017) and older (2010) McDonald criteria at time point of diagnosis and two years after study inclusion sNfL levels correlated with number of T2 and Gd+ lesions and clinical relapses. After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036) and increased accuracy of distinction between CIS and RRMS, when including ≥ 90th percentile of sNfL values. Patients receiving disease-modifying treatment (DMT) during the first two years had higher sNfl baseline levels (11.8 pg/ml, 7.5-20.9 pg/ml, n = 727) than patients never receiving DMT (9.5 pg/ml, IQR 6.4-14.1 pg/ml, n = 87, p = 0.002). Longitudinal sNfL levels reflected treatment decisions within the first four years.

Conclusions

sNfL is associated with diagnosis and prognosis of MS patients at the time point of first diagnosis and may be of use for initial treatment stratification.

Collapse
Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0707 - Costs and health-related quality of life in patients with neuromyelitis optica spectrum disorder and MOG-antibody associated disease (CHANCENMO-Study) (ID 1015)

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOG-AD) are orphan diseases with high impact on quality of life and to date unknown socio-economic burden.

Objectives

The aim of this study was to evaluate costs and health-related quality of life of NMOSD and MOG-AD from the societal perspective.

Methods

In a multicenter cross-sectional study throughout Germany between 04/2017 and 04/2019, the primary data on retrospective consumption of medical and non-medical resources and work ability related to NMOSD and MOG-AD were assessed via standardized and pre-tested paper-based patient questionnaires. Health-related quality of life was captured by the EuroQoL Group EQ-5D-5L questionnaire. Clinical data were retrieved from the Neuromyelitis Optica Study Group (NEMOS) database. Patient recruitment took place at 17 German NEMOS centers. Costs were analyzed in EUR for 2018.

Results

During the recruitment period, 218 of 275 adult patients were screened for eligibility. 212 patients (80.2% women; mean age 49 ± SD 15 years; mean disease duration 9 ± SD 8.5 years; Expanded Disability Status Scale (EDSS) 3.7 ± SD 2.1) were analyzed. The mean total annual per capita cost of illness accounted for EUR 59 576 and the mean index value of the EQ-5D-5L was 0.693. Given an estimated prevalence of NMOSD in Germany of 1.3/100 000, the annual burden from the societal perspective adds to EUR 64.3 Mio for Germany. The most important cost drivers were informal care costs (27.6% of total costs), indirect costs (23.3%; particularly loss of salary) and drugs, especially immunotherapeutics (16.4%). Costs showed a significant positive correlation with disease severity (p<0.0001); in the EDSS 6.5-8.5 subgroup the annual costs were EUR 129 436. Moreover, the health-related quality of life revealed a negative correlation with disease severity (p<0.0001); in the EDSS 6.5-8.5 subgroup the mean index value was 0.195.

Conclusions

These German data from the era without approved standard medications show enormous effects of the disease on costs and quality of life and might be helpful for estimating the impact and cost-effectiveness of new therapeutic approaches.

Collapse