Diroximel fumarate in the treatment of multiple sclerosis

2020 ◽  
Vol 10 (5) ◽  
pp. 267-276 ◽  
Author(s):  
Elise Jonasson ◽  
Tobias Sejbaek
Keyword(s):  
Multiple Sclerosis ◽  
Dimethyl Fumarate ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
First Line ◽  
Promising Alternative ◽  
Current Review ◽  
Phase Iii Trials ◽  
Monomethyl Fumarate ◽  
Gastrointestinal Adverse Events

Diroximel fumarate (DRF) is a new emerging therapy for patients with multiple sclerosis. The levels of its active metabolite, monomethyl fumarate, are bioequivalent to the levels generated from dimethyl fumarate (DMF) treatment. The efficacy and safety profiles of DRF are expected to be similar to the well-established profiles of DMF. The metabolism of DRF leads to lower concentration of methanol in the small intestine than with DMF and thus reduced severity and frequency of gastrointestinal adverse events. DRF seems a promising alternative to DMF and other first-line therapies for multiple sclerosis. The current review is based on the two existing Phase III trials of DRF: the interim analysis of the EVOLVE-MS-1 trial and the completed EVOLVE-MS-2 trial.

scholarly journals Pharmacotherapy Options for Multiple Sclerosis: Focus on Natalizumab

2010 ◽  
Vol 2 ◽  
pp. CMT.S2043 ◽  
Author(s):  
Martin Stangel ◽  
Bernd C. Kieseier
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Safety Management ◽  
Jc Virus ◽  
Unmet Need ◽  
Neurological Impairment ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
Phase Iii Trials

Multiple sclerosis (MS) is considered an autoimmune disease causing demyelination in the central nervous system (CNS) that subsequently leads to axonal damage and neurological impairment. Currently available first line therapies are based on immunomodulation with beta-interferons or glatirameracetate. However, these treatments are only partially effective, thus, more powerful therapies represent an unmet need in MS. Natalizumab is a monoclonal antibody targeting the α4β1 integrin that has been shown to be crucial in the process of transmigration of immunocompetent cells across the blood-brain-barrier (BBB) into the CNS. Two phase III trials have demonstrated clinical and paraclinical efficacy of natalizumab and recent data suggest that many patients that have failed on a first-line disease modifying drug (DMD) benefit from a treatment with natalizumab. Unfortunately, since the licensing of natalizumab in 2006 there have been 75 cases of progressive multifocal leukoencephalopathy (PML) reported. This rare, but potentially fatal infection of the brain by JC-virus restricts the use of natalizumab. Currently there are attempts to define algorithms based on the identification of risk factors for the development of PML to achieve a better safety management for MS patients treated with this monoclonal antibody.

scholarly journals Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies

2021 ◽  
Vol 13 ◽  
pp. 117957352110287
Author(s):  
Jiwon Oh ◽  
Sandra Vukusic ◽  
Klaus Tiel-Wilck ◽  
Jihad Said Inshasi ◽  
David Rog ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Age Groups ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Additional Group ◽  
Disability Status ◽  
Scale Scores ◽  
Post Hoc ◽  
Phase Ii And Iii

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies. Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed. Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups. Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

scholarly journals Efficacy and Safety of Moxifloxacin in Hospitalized Patients with Secondary Peritonitis: Pooled Analysis of Four Randomized Phase III Trials

2014 ◽  
Vol 15 (5) ◽  
pp. 567-575 ◽  
Author(s):  
Jan J. De Waele ◽  
Jose M. Tellado ◽  
Günter Weiss ◽  
Jeffrey Alder ◽  
Frank Kruesmann ◽  
...  
Keyword(s):  
Pooled Analysis ◽  
Hospitalized Patients ◽  
Secondary Peritonitis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Phase Iii Trials

Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing–remitting multiple sclerosis: findings from the CONFIRM study

2013 ◽  
Vol 20 (2) ◽  
pp. 253-257 ◽  
Author(s):  
Mariko Kita ◽  
Robert J Fox ◽  
J Theodore Phillips ◽  
Michael Hutchinson ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Short Form ◽  
Dimethyl Fumarate ◽  
Phase Iii ◽  
Health Related Quality ◽  
Relapsing Remitting ◽  
Related Quality ◽  
Health Related

Multiple sclerosis (MS) has a significant impact on health-related quality of life (HRQoL) with symptoms adversely affecting many aspects of everyday living. BG-12 (dimethyl fumarate) demonstrated significant efficacy in the phase III studies DEFINE and CONFIRM in patients with relapsing–remitting MS. In CONFIRM, HRQoL was worse in patients with greater disability at baseline, and who relapsed during the study, and improved with BG-12 treatment. Mean Short Form-36 Physical Component Summary scores for BG-12 increased over 2 years and scores for placebo decreased. Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS.

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

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