Clinical Trial, Phase III Clinical Trial, Phase IV Journal Article Multicenter Study Ppublish 1 citation
PubMed: 39570545 DOI: 10.1007/s12325-024-03047-w
Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients.
Adv Ther 42(1):395-412
Authors: Yang Mao-Draayer, Amit Bar-Or, Konstantin Balashov, John Foley, Kyle Smoot, Erin E Longbrake, Derrick Robertson, Jason P Mendoza, James B Lewin, Nicholas Everage, Ivan Božin, Jennifer Lyons, Oksana Mokliatchouk, Eris Bame, Fabrizio Giuliani
Affiliations
- Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Boston University School of Medicine, Boston, MA, USA.
- Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, UT, USA.
- Providence MS Center, Providence Brain and Spine Institute, Portland, OR, USA.
- Yale University, New Haven, CT, USA.
- University of South Florida College of Medicine, Tampa, FL, USA.
- Biogen, Cambridge, MA, USA.
- Biogen, Cambridge, MA, USA.
- Biogen, Baar, Switzerland.
- Department of Internal Medicine and Department of Experimental Medicine, University of Genoa, Genoa, Italy.
- University of Alberta, Edmonton, AB, Canada.
Abstract
INTRODUCTION
Real-world studies in the USA report that 41-56% of patients with multiple sclerosis (MS) are ≥ 50 years old, yet data on their response to disease-modifying therapies (DMTs) is limited. Dimethyl fumarate (DMF) is an oral DMT approved for treating relapsing MS. This analysis evaluated the safety, efficacy, and immunophenotype changes of DMF in patients ≥ 50 years compared with patients < 50 years.
METHODS
ESTEEM, a 5-year, real-world, observational phase 4 study, assessed the safety and effectiveness of DMF, including treatment-emergent serious adverse events (SAEs) and adverse events (AEs) leading to treatment discontinuation. Absolute lymphocyte counts (ALCs) were recorded from a subset of patients. The PROCLAIM study, a phase 3b interventional study, reported safety outcomes and lymphocyte subset changes in patients with relapsing-remitting MS (RRMS) treated with DMF. The study evaluated safety outcomes by analyzing the incidence of SAEs and detailed changes in CD4 + and CD8 + T cell compartments over 96 weeks of DMF treatment.
RESULTS
ESTEEM included 4020 patients aged < 50 years and 1069 aged ≥ 50 years. AEs leading to discontinuation were reported by 19.6% patients < 50 years and 29.6% of patients ≥ 50 years, with gastrointestinal disorders being the most common. SAEs were reported by 5.2% of patients < 50 years and 8.9% those ≥ 50 years. In PROCLAIM, SAEs were reported in 13% of patients < 50 years and 10% of those ≥ 50 years. Median ALC decreased by 35% in patients < 50 years and 50% in those ≥ 50 years in ESTEEM, with similar patterns observed in PROCLAIM.
CONCLUSIONS
ESTEEM found no unexpected safety signals in older patients and annualized relapse rates (ARRs) were significantly reduced in both age groups. Both studies indicated that DMF is efficacious and has a favorable safety profile in patients with RRMS aged ≥ 50 years.
CLINICAL TRIAL REGISTRATION
ESTEEM (NCT02047097), PROCLAIM (NCT02525874).
MeSH
Equipment And Supplies, Safety, Lymphocytes, Dimethyl Fumarate, Drug Therapy, Aged, Drug-Related Side Effects And Adverse Reactions, Fumarates, Diagnosis, Therapeutics