Trial reportAdvances in therapy2019
Improving the Gastrointestinal Tolerability of Fumaric Acid Esters: Early Findings on Gastrointestinal Events with Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis from the Phase 3, Open-Label EVOLVE-MS-1 Study.
Trial report in Advances in therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02634307 (A Phase 3 Open Label Study to Evaluate the Long-term Safety and Tolerability of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis), which is not on this map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3 Open Label Study to Evaluate the Long-term Safety and Tolerability of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis
Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Trial
- Comparative Effectiveness of Diroximel Fumarate vs. Dimethyl Fumarate in Persons with Multiple Sclerosis: A US Claims Analysis of Relapse Outcomes.Advances in therapy · 2026Article
- A Randomised, Double-Blind Study Comparing the Gastrointestinal Tolerability of Tegomil Fumarate Versus Dimethyl Fumarate in Healthy Volunteers.Neurology and therapy · 2026Article
- Diroximel Fumarate-Loaded Solid Lipid Nanoparticles (DRF-SLNs) as Potential Carriers for the Treatment of Multiple Sclerosis: Preformulation Study.International journal of molecular sciences · 2025Article
- Patient and healthcare provider experience of diroximel fumarate: considerations for selecting disease-modifying therapy.Neurodegenerative disease management · 2025Article
- Dimethyl Fumarate vs. Monomethyl Fumarate: Unresolved Pharmacologic Issues.Pharmaceutics · 2025Review
- Comparative activity of dimethyl fumarate derivative IDMF in three models relevant to multiple sclerosis and psoriasis.FEBS open bio · 2025Article
- Diroximel Fumarate Acts Through Nrf2 to Attenuate Methylglyoxal-Induced Nociception in Mice and Decrease ISR Activation in DRG Neurons.Diabetes · 2025Article
- Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.Clinical drug investigation · 2024Observational
- Exploring the top 30 drugs associated with drug-induced constipation based on the FDA adverse event reporting system.Frontiers in pharmacology · 2024Article
- Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decreases ISR activation in DRG neurons.bioRxiv : the preprint server for biology · 2023Article
- Letter to the Editor Regarding: "Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis".Neurology and therapy · 2023Article
- Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Article
- Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Novel Gastroprotective and Thermostable Cocrystal of Dimethyl Fumarate: Its Preparation, Characterization, andACS omega · 2023Article
- Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders.International journal of molecular sciences · 2023Review
- Identification of galectin-1 and other cellular targets of alpha,beta-unsaturated carbonyl compounds, including dimethylfumarate, by use of click-chemistry probes.Redox biology · 2023Article
- Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis.Neurology and therapy · 2023Article
- Novel potential pharmacological applications of dimethyl fumarate-an overview and update.Frontiers in pharmacology · 2023Review
- Disease-modifying therapies for relapsing/active secondary progressive multiple sclerosis - a review of population-specific evidence from randomized clinical trials.Therapeutic advances in neurological disorders · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
introductionDiroximel fumarate (DRF) is a novel oral fumarate in development for patients with relapsing forms of multiple sclerosis (MS). Clinical findings from the DRF development program suggest that rates of gastrointestinal (GI) treatment-emergent adverse events (TEAEs) and discontinuation due to GI TEAEs are low, based on clinical and real-world observations of other fumaric acid esters, including dimethyl fumarate (DMF). The incidence of GI TEAEs varies from 40 to 88% in clinical and real-world studies of DMF. The objective of this study is to present GI tolerability findings from the EVOLVE-MS-1 study and present biologic hypotheses for the improved GI properties of DRF.
methodsGI TEAEs and treatment discontinuation because of GI TEAEs were assessed in DRF-treated patients with relapsing-remitting MS who were participating in the ongoing, 96-week, open-label, phase 3 EVOLVE-MS-1 study.
resultsAs of March 30, 2018, a total of 696 patients were enrolled in EVOLVE-MS-1. GI TEAEs were reported in 30.9% (215/696) of patients; the vast majority (96%; 207/215) experienced events that were mild or moderate in severity. When GI AEs did occur, they occurred early in treatment, resolved (88.8%; 191/215), and were of short duration [median 7.5 (range 1-87) days] in most patients. GI TEAEs led to < 1% of patients discontinuing treatment.
conclusionsWe suggest that the distinct chemical structure of DRF contributes to the observed low rates of GI TEAEs and GI-associated treatment discontinuations, possibly due to a combination of several factors. We hypothesize that these factors may include less reactivity with off-target proteins and/or lower production of a methanol leaving group that may contribute to GI irritation. A direct comparison of GI tolerability with DRF versus DMF is being evaluated in the EVOLVE-MS-2 study.
trial registrationClinicalTrials.gov number NCT02634307.
fundingAlkermes Inc. (Waltham, MA, USA) and Biogen (Cambridge, MA, USA).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.