scholarly journals Comparative effectiveness of delayed-release dimethyl fumarate versus glatiramer acetate in multiple sclerosis patients: results of a matching-adjusted indirect comparison

2017 ◽  
Vol 6 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Andrew Chan ◽  
Gary Cutter ◽  
Robert J Fox ◽  
James Xiao ◽  
James B Lewin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Comparative Effectiveness ◽  
Indirect Comparison ◽  
Dimethyl Fumarate ◽  
Delayed Release ◽  
Adjusted Indirect Comparison ◽  
Multiple Sclerosis Patients

Evidence of activation of the Nrf2 pathway in multiple sclerosis patients treated with delayed-release dimethyl fumarate in the Phase 3 DEFINE and CONFIRM studies

2017 ◽  
Vol 23 (14) ◽  
pp. 1875-1883 ◽  
Author(s):  
Sreeja Gopal ◽  
Alvydas Mikulskis ◽  
Ralf Gold ◽  
Robert J Fox ◽  
Katherine T Dawson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ex Vivo ◽  
Dimethyl Fumarate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Phase 3 ◽  
Potent Inducer ◽  
Nrf2 Pathway ◽  
Delayed Release ◽  
Multiple Sclerosis Patients

Background: Delayed-release dimethyl fumarate (DMF) is an approved oral treatment for relapsing forms of multiple sclerosis (MS). Preclinical studies demonstrated that DMF activated the nuclear factor E2–related factor 2 (Nrf2) pathway. DMF and its primary metabolite monomethyl fumarate (MMF) were also shown to promote cytoprotection of cultured central nervous system (CNS) cells via the Nrf2 pathway. Objective: To investigate the activation of Nrf2 pathway following ex vivo stimulation of human peripheral blood mononuclear cells (PBMCs) with DMF or MMF, and in DMF-treated patients from two Phase 3 relapsing MS studies DEFINE and CONFIRM. Methods: Transcription of Nrf2 target genes NADPH:quinone oxidoreductase-1 (NQO1) and heme-oxygenase-1 (HO1) was measured using Taqman® assays. RNA samples were isolated from ex vivo–stimulated PBMCs and from whole blood samples of 200 patients each from placebo, twice daily (BID) and three times daily (TID) treatments. Results: DMF and MMF induced NQO1 and HO1 gene expression in ex vivo–stimulated PBMCs, DMF being the more potent inducer. Induction of NQO1 occurred at lower DMF concentrations compared to that of HO1. In DMF-treated patients, a statistically significant induction of NQO1 was observed relative to baseline and compared to placebo. No statistical significance was reached for HO1 induction. Conclusion: These data provide the first evidence of Nrf2 pathway activation from two large pivotal Phase 3 studies of DMF-treated MS patients.

Real-world patient characteristics, treatment patterns and costs in relapsing multiple sclerosis patients treated with glatiramer acetate, dimethyl fumarate or teriflunomide in Germany

2021 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Anna Kurzeja ◽  
Bogdan Muresan ◽  
Jennifer S Haas ◽  
Jessica Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Patient Characteristics ◽  
Dimethyl Fumarate ◽  
Healthcare Resource Utilization ◽  
Disease Modifying Therapies ◽  
High Adherence ◽  
Treatment Naïve ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Aim: To evaluate adherence, healthcare resource utilization (HRU) and costs for glatiramer acetate (GA; injectable), dimethyl fumarate (oral) and teriflunomide (oral) in relapsing multiple sclerosis. Patients & methods: Retrospective analyses of a claims database. Results: Teriflunomide patients were older with more co-morbidities and fewer relapses versus GA and dimethyl fumarate. GA patients were mostly disease-modifying therapies (DMTs)-treatment naive. Treatment adherence was 61–70%. All DMTs reduced HRU versus pre-index. Costs were comparable across cohorts. High adherence reduced hospitalizations and several costs versus low adherers. Conclusion: Adherence rates were high and comparable with all DMTs. Similar (and high) reductions in HRU and costs occurred with all DMTs. High adherence improved economic outcomes versus low adherence. Thus, investing in adherence improvement is beneficial to improve outcomes in relapsing multiple sclerosis.

scholarly journals Safety and Tolerability of Delayed-Release Dimethyl Fumarate Administered with Interferon Beta or Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis

2016 ◽  
Vol 18 (3) ◽  
pp. 138-146 ◽  
Author(s):  
Jonathan Calkwood ◽  
Timothy Vollmer ◽  
Robert J. Fox ◽  
Ray Zhang ◽  
Mark Novas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Glatiramer Acetate ◽  
Safety Profile ◽  
Interferon Beta ◽  
Dimethyl Fumarate ◽  
Delayed Release ◽  
Normal Limits ◽  
Increased Risk ◽  
Relapsing Remitting

Background: Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for relapsing multiple sclerosis (MS). The objective of this study was to explore the safety and tolerability of DMF when administered with interferon beta (IFNβ) or glatiramer acetate (GA). Methods: Patients with relapsing-remitting MS receiving established therapy with the same dose of IFNβ or GA for at least 12 months continued their prescribed therapy for 2 months (monotherapy period) and then received DMF 240 mg three times daily in addition to their prescribed MS therapy for 6 months (add-on therapy period). Safety and magnetic resonance imaging outcomes were monitored monthly. Results: During the add-on therapy period, in the DMF+IFNβ (n = 57) and DMF+GA (n = 47) groups, the overall incidence of adverse events was 95% and 100%, respectively; the most common adverse events were flushing, diarrhea, and abdominal pain. In both groups, mean lymphocyte counts decreased but remained within normal limits, and hepatic transaminase levels increased transiently; no case met Hy's law criteria. There was no overall increased risk of infection. In both groups, gadolinium-enhancing lesion activity and new/enlarging T2 lesions decreased compared with the monotherapy period (exploratory endpoints). Conclusions: The safety profile of DMF taken with IFNβ or GA was acceptable and consistent with the known safety profile of DMF monotherapy.

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