Background:
Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing–remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure ...to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF’s distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile.
Objective:
To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study.
Methods:
EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory.
Results:
As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1–98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13–0.20).
Conclusion:
Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS.
Background:
Diroximel fumarate (DRF) is a novel oral fumarate approved for relapsing forms of multiple sclerosis (MS). DRF demonstrated significantly improved gastrointestinal (GI) tolerability ...versus dimethyl fumarate (DMF) with fewer days of Individual Gastrointestinal Symptom and Impact Scale (IGISIS) scores ⩾2, GI adverse events (AEs), and treatment discontinuations due to GI AEs. Our aim was to evaluate the impact of GI tolerability events on quality of life (QoL) for patients with relapsing–remitting MS who received DRF or DMF in EVOLVE-MS-2.
Methods:
A post hoc analysis was conducted in patients who were enrolled in the randomized, blinded, 5-week, EVOLVE-MS-2 ClinicalTrials.gov identifier: NCT03093324 study of DRF versus DMF. Patients completed daily IGISIS and Global GISIS (GGISIS) eDiary questionnaires to assess GI symptom intensity and interference with daily activities and work.
Results:
In total, 504 patients (DRF, n = 253; DMF, n = 251) received study drug and 502 (DRF, n = 253; DMF, n = 249) completed at least one post-baseline questionnaire. With DRF, GI symptoms were less likely to interfere ‘quite a bit’ or ‘extremely’ with regular daily activities IGISIS: DRF, 9.5% (24/253) versus DMF, 28.9% (72/249) or work productivity GGISIS: DRF, 6.1% (10/165) versus DMF, 11.3% (18/159). DRF-treated patients had fewer days with ⩾1 h of missed work (DRF, 43 days, n = 20 versus DMF, 88 days, n = 26). DMF-treated patients reported highest GI symptom severity and missed work at week 2–3 shortly after completing the titration period, which coincided with the majority of GI-related treatment discontinuations 58.3% (7/12). GI tolerability AEs DRF, 34.8% (88/253); DMF, 48.2% (121/251), concomitant symptomatic medication use DRF, 19.3% (17/88) versus DMF, 30.6% (37/121), and GI-related discontinuations (DRF, 0.8% versus DMF, 4.8%) were lower with DRF versus DMF.
Conclusions:
The improved GI tolerability with DRF translated into clinically meaningful benefits to QoL, as patients experienced less impact on daily life and work and required less concomitant symptomatic medication use.
Trial registration:
ClinicalTrials.gov identifier: NCT03093324
Background
Little is known about quality of life (QOL) at the time of multiple sclerosis (MS) or clinically isolated syndrome (CIS) diagnosis and how it evolves in the critical adjustment period ...immediately following a new diagnosis.
Objectives
To (1) describe QOL trajectory in the first year post-MS/CIS diagnosis and (2) examine associations of demographic and biopsychosocial factors with QOL at baseline and as it evolves over the first year post-MS/CIS diagnosis.
Methods
Participants were
N
= 250 individuals newly diagnosed with MS or CIS. Participants completed self-report assessments of QOL, demographics, and biopsychosocial factors at 1, 2, 3, 6, 9, and 12 months post-diagnosis using validated measures.
Results
At 1-month post-diagnosis, QOL
M
= 75.2/100 with subsequent assessments revealing consistent ratings on average. Modelling revealed a small number of variables that were predictive of QOL at baseline and/or change in QOL over time.
Conclusion
QOL in the first year post-MS/CIS diagnosis was, on average, high and stable. A subset of modifiable factors across the biopsychosocial spectrum was associated with baseline level of QOL and change in QOL over time. The stability in QOL suggests that patients can be assessed early after diagnosis for key variables that are predictive of both current and future QOL.
Background:
Diroximel fumarate (DRF) is approved for adults with relapsing–remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate ...(DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF.
Objective:
To report final outcomes from EVOLVE-MS-1.
Methods:
EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory.
Results:
Overall, 75.7% (800/1057) of patients completed the study; median exposure was 1.8 (range: 0.0–2.0) years. AEs occurred in 938 (88.7%) patients, mostly of mild (28.9%) or moderate (50.3%) severity. DRF was discontinued due to AEs in 85 (8.0%) patients, with < 2% discontinuing due to GI or flushing/flushing-related AEs. At Week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (72.7%; p < 0.0001); adjusted annualized relapse rate was 0.13 (95% confidence interval: 0.11–0.15).
Conclusion:
DRF was generally well tolerated over 2 years, with few discontinuations due to AEs; radiological measures indicated decreased disease activity from baseline. These outcomes support DRF as a treatment option in patients with RRMS.
Background:
Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system ...function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body.
Objective:
This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists.
Methods:
Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA’s Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose.
Results:
Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk.
Conclusion:
Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.
Pregnancy in multiple sclerosis (MS) is considered safe for both the woman and the child. Nevertheless, pregnancy issues in MS are complex both from a patient’s and a provider’s perspective. In an ...anonymous survey, 28 healthcare providers in the United States reported on the management of multiple sclerosis (MS) during pregnancy. Participants were asked about their recommendations to patients about the use of disease modifying therapies during pregnancy and breastfeeding and general recommendations about MS and pregnancy. Healthcare providers were also asked about sources from which they receive information about the management of patients with MS. Results suggested that healthcare providers do not discourage pregnancy for women with MS, recommend that women not use disease modifying therapies while pregnant, and have a positive view of breastfeeding for women with MS. Results also indicated the need for guidelines on patient management for pregnant women with MS.
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