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

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

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. 2024 Nov 21. doi: 10.1007/s12325-024-03047-w. Online ahead of print.

Authors

Yang Mao-Draayer¹, Amit Bar-Or², Konstantin Balashov³, John Foley⁴, Kyle Smoot⁵, Erin E Longbrake⁶, Derrick Robertson⁷, Jason P Mendoza⁸, James B Lewin⁹, Nicholas Everage⁸, Ivan Božin¹⁰, Jennifer Lyons⁸, Oksana Mokliatchouk⁸, Eris Bame^{8

11}, Fabrizio Giuliani¹²

Affiliations

¹ Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
² Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ Boston University School of Medicine, Boston, MA, USA.
⁴ Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, UT, USA.
⁵ Providence MS Center, Providence Brain and Spine Institute, Portland, OR, USA.
⁶ Yale University, New Haven, CT, USA.
⁷ University of South Florida College of Medicine, Tampa, FL, USA.
⁸ Biogen, Cambridge, MA, USA.
⁹ Biogen, Cambridge, MA, USA. Jim.lewin@biogen.com.
¹⁰ Biogen, Baar, Switzerland.
¹¹ Department of Internal Medicine and Department of Experimental Medicine, University of Genoa, Genoa, Italy.
¹² University of Alberta, Edmonton, AB, Canada.

PMID: 39570545
DOI: 10.1007/s12325-024-03047-w

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).

Keywords: Dimethyl fumarate; Effectiveness; Real-world evidence; Relapsing multiple sclerosis; Safety.

Associated data

ClinicalTrials.gov/NCT02525874
ClinicalTrials.gov/NCT02047097