2024
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
Mao-Draayer Y, Bar-Or A, Balashov K, Foley J, Smoot K, Longbrake E, Robertson D, Mendoza J, Lewin J, Everage N, Božin I, Lyons J, Mokliatchouk O, Bame E, Giuliani F. 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. Advances In Therapy 2024, 1-18. PMID: 39570545, DOI: 10.1007/s12325-024-03047-w.Peer-Reviewed Original ResearchAbsolute lymphocyte countRelapsing-remitting MSEffect of dimethyl fumarateAnnualized relapse rateDisease-modifying therapiesAdverse eventsDimethyl fumarateCD8+ T cell compartmentMultiple sclerosisOlder patientsMedian absolute lymphocyte countOral disease-modifying therapyTreated with dimethyl fumarateSafety outcomesTreating relapsing MST cell compartmentPhase 3 studyResponse to disease-modifying therapiesIncidence of SAEsLymphocyte subset changesReal-world safetyTreatment discontinuationCD4+Immunophenotypic changesRelapse rate
2021
A New England COVID-19 Registry of Patients With CNS Demyelinating Disease
Money KM, Mahatoo A, Samaan S, Anand P, Baber U, Bailey M, Bakshi R, Bouley A, Bower A, Cahill J, Houtchens M, Katz J, Lathi E, Levit E, Longbrake EE, McAdams M, Napoli S, Raibagkar P, Wade P, Sloane JA. A New England COVID-19 Registry of Patients With CNS Demyelinating Disease. Neurology Neuroimmunology & Neuroinflammation 2021, 8: e1046. PMID: 34341094, PMCID: PMC8362350, DOI: 10.1212/nxi.0000000000001046.Peer-Reviewed Original ResearchConceptsCOVID-19 infectionHospitalization ratesRisk factorsSevere coronavirus disease 2019 (COVID-19) infectionDisease-modifying therapy useCoronavirus disease 2019 (COVID-19) infectionStepwise multivariate logistic regressionCNS Demyelinating DiseaseNausea/vomitingAbsolute lymphocyte countIndependent risk factorNumber of comorbiditiesDisease 2019 infectionPatient risk factorsRisk of hospitalizationCOVID-19 cohortDisease-modifying therapiesCase fatality rateMultivariate logistic regressionCOVID-19 registryFisher's exact testDemyelinating diseaseClinical characteristicsLymphocyte countNeurologic symptoms
2020
Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity
Longbrake EE, Mao-Draayer Y, Cascione M, Zielinski T, Bame E, Brassat D, Chen C, Kapadia S, Mendoza JP, Miller C, Parks B, Xing D, Robertson D. Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity. Multiple Sclerosis Journal 2020, 27: 883-894. PMID: 32716690, PMCID: PMC8023410, DOI: 10.1177/1352458520937282.Peer-Reviewed Original ResearchConceptsDelayed-release dimethyl fumarateAbsolute lymphocyte countT cellsMedian absolute lymphocyte countEffector memory T cellsDimethyl fumarate treatmentPhase 3b studyTotal T cellsAdverse event ratesMemory T cellsProtective humoral immunityForms of MSDMF BIDLymphocyte subsetsAdverse eventsLymphocyte countTotal IgAImmune environmentImmunoglobulin levelsNaive CD4Sustained efficacyHumoral immunityFumarate treatmentSubclass levelsCount changesAbsolute Lymphocyte Counts Are Not a Biomarker of Clinical Response in Patients Treated With Delayed-Release Dimethyl Fumarate (830)
Longbrake E, Mao-Draayer Y, Matthews P, Foley J, Zieliński T, Chen C, Mokliatchouk O, Parks B, Sharma A, Xing D, Kapadia S, Bame E. Absolute Lymphocyte Counts Are Not a Biomarker of Clinical Response in Patients Treated With Delayed-Release Dimethyl Fumarate (830). Neurology 2020, 94 DOI: 10.1212/wnl.94.15_supplement.830.Peer-Reviewed Original ResearchRelease Dimethyl FumarateAbsolute lymphocyte countClinical responseLymphocyte countDimethyl fumaratePatientsBiomarkers
2017
Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count
Longbrake EE, Cantoni C, Chahin S, Cignarella F, Cross AH, Piccio L. Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count. Multiple Sclerosis Journal 2017, 24: 728-738. PMID: 28480794, PMCID: PMC5665729, DOI: 10.1177/1352458517707069.Peer-Reviewed Original ResearchConceptsAbsolute lymphocyte countDMF-treated patientsPeripheral blood mononuclear cellsDimethyl fumarateLymphocyte countPeptide stimulationLow absolute lymphocyte countFollicular T helper cellsDMF-induced lymphopeniaInvariant T (MAIT) cellsPro-inflammatory cytokinesT-cell phenotypeBlood mononuclear cellsT cell productionT helper cellsT lymphocyte functionMemory B cellsActivation-induced cell deathMultiparametric flow cytometryUntreated patientsMultiple sclerosisMononuclear cellsHealthy controlsT cellsT lymphocytes
2015
Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients
Longbrake E, Ramsbottom M, Cantoni C, Ghezzi L, Cross A, Piccio L. Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients. Multiple Sclerosis Journal 2015, 22: 1061-1070. PMID: 26459150, PMCID: PMC4829494, DOI: 10.1177/1352458515608961.Peer-Reviewed Original ResearchConceptsDMF-treated patientsMemory T cellsMultiple sclerosis patientsT cellsMS patientsDendritic cellsSclerosis patientsEffector memory T cellsUntreated MS patientsMyeloid dendritic cellsAbsolute lymphocyte countPlasmacytoid dendritic cellsNatural killer cellsNaïve T cellsMechanism of actionLymphocyte countLymphopenic patientsRegulatory cellsKiller cellsPeripheral bloodImmune cellsHealthy controlsPatientsB cellsFlow cytometryDimethyl fumarate-associated lymphopenia: Risk factors and clinical significance
Longbrake EE, Naismith RT, Parks BJ, Wu GF, Cross AH. Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance. Multiple Sclerosis Journal - Experimental Translational And Clinical 2015, 1: 2055217315596994. PMID: 26550483, PMCID: PMC4636217, DOI: 10.1177/2055217315596994.Peer-Reviewed Original ResearchDimethyl fumarateMultiple sclerosisRisk factorsClinical significanceGrade 2Lower baseline absolute lymphocyte countBaseline absolute lymphocyte countSingle academic medical centerDMF-induced lymphopeniaDMF-treated patientsRetrospective cohort studyAbsolute lymphocyte countGood clinical responseProgressive multifocal leukoencephalopathyDisease-modifying therapiesFraction of patientsReal-world populationAcademic medical centerLymphocyte monitoringNatalizumab exposureMultifocal leukoencephalopathyClinical responseCohort studyLymphocyte countOlder patients