2024
US Clinical Practice Experience with Eculizumab in Myasthenia Gravis: Acute Clinical Events and Healthcare Resource Utilization
Nowak R, Habib A, Klink A, Muppidi S, Parthan A, Sader S, Balanean A, Gajra A, Howard J. US Clinical Practice Experience with Eculizumab in Myasthenia Gravis: Acute Clinical Events and Healthcare Resource Utilization. Drugs - Real World Outcomes 2024, 11: 593-601. PMID: 39470958, PMCID: PMC11589080, DOI: 10.1007/s40801-024-00457-8.Peer-Reviewed Original ResearchHealthcare resource utilizationAssociated healthcare resource utilizationRescue therapy useEculizumab treatmentMyasthenia gravisMG exacerbationEculizumab initiationTherapy useMethodsA retrospective chart reviewTerminal complement inhibitor eculizumabRetrospective chart review analysisRates of healthcare resource utilizationComplement inhibitor eculizumabGeneralized myasthenia gravisRetrospective chart reviewChart review analysisTreatment of patientsUS adultsEculizumab therapyAcute clinical eventsMG crisisRescue therapyChart reviewEculizumabTherapy administrationFluorescence-detection size-exclusion chromatography specifically detects autoantibodies targeting the ganglionic acetylcholine receptor in patients with autoimmune autonomic ganglionopathy
Baxter L, Hopkins S, O'Connor K, Pham M, Nowak R, Monson N, Blackburn K, Hibbs R, Vernino S, Noviello C. Fluorescence-detection size-exclusion chromatography specifically detects autoantibodies targeting the ganglionic acetylcholine receptor in patients with autoimmune autonomic ganglionopathy. Journal Of Neuroimmunology 2024, 396: 578454. PMID: 39277987, DOI: 10.1016/j.jneuroim.2024.578454.Peer-Reviewed Original ResearchAutoimmune autonomic ganglionopathyGanglionic acetylcholine receptorAutonomic ganglionopathyRadioimmunoprecipitation assayFluorescence-detection size-exclusion chromatographyAcetylcholine receptorsAutoantibody detectionClinical symptomsDetect autoantibodiesAutoimmune diseasesHealthy controlsPatient seraSize-exclusion-chromatographyAutoantibodiesGAChRGanglionopathySize exclusion chromatographyPatientsReceptorsUnited States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use
Habib A, Klink A, Muppidi S, Parthan A, Sader S, Balanean A, Gajra A, Nowak R, Howard J. United States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use. Journal Of Neurology 2024, 271: 6114-6126. PMID: 39052039, PMCID: PMC11377470, DOI: 10.1007/s00415-024-12569-w.Peer-Reviewed Original ResearchMinimal symptom expression’Minimal manifestation statusGeneralized myasthenia gravisEculizumab initiationEculizumab treatmentTotal scoreMG-ADLPrednisone dosageMyasthenia gravisMethodsA retrospective chart reviewComplement C5 inhibitor eculizumabSteroid-sparing effectAssociated with sustained improvementOpen-label extensionEffectiveness of eculizumabImmunosuppressive therapy useConcomitant medication useRetrospective chart reviewNonsteroidal immunosuppressive therapyMyasthenia Gravis-ActivitiesTreatment-refractoryC5 inhibitor eculizumabDiscontinue prednisoneImmunosuppressive therapySymptom expressionProteomic Analysis Reveals a Distinct Immunological Signature for Late-onset Myasthenia Gravis (S15.003)
Roy B, Habiabadi F, O’Connor K, Nowak R, Kaminski H. Proteomic Analysis Reveals a Distinct Immunological Signature for Late-onset Myasthenia Gravis (S15.003). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205944.Peer-Reviewed Original ResearchTrial Design and Impact on Study Outcome: Post-hoc Analysis of the BeatMG Study Based on RINOMAX Trial Criteria (P4-11.004)
Roy B, Nowak R. Trial Design and Impact on Study Outcome: Post-hoc Analysis of the BeatMG Study Based on RINOMAX Trial Criteria (P4-11.004). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205956.Peer-Reviewed Original ResearchPhenotypes of B Cells Producing Autoantibodies in MOGAD Patients (N1.002)
Filipek B, Yandamuri S, Obaid A, Thurman J, Makhani N, Nowak R, Guo Y, Lucchinetti C, Flanagan E, Longbrake E, O’Connor K. Phenotypes of B Cells Producing Autoantibodies in MOGAD Patients (N1.002). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000208259.Peer-Reviewed Original ResearchEffectiveness of Eculizumab Treatment by Time from Diagnosis in Patients with Generalized Myasthenia Gravis: A Retrospective Electronic Medical Record Analysis (S15.006)
Muppidi S, Lee J, Habib A, Howard J, Klink A, Kielhorn A, Sabatella G, Nowak R. Effectiveness of Eculizumab Treatment by Time from Diagnosis in Patients with Generalized Myasthenia Gravis: A Retrospective Electronic Medical Record Analysis (S15.006). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205156.Peer-Reviewed Original ResearchA Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.
Yandamuri S, Filipek B, Lele N, Cohen I, Bennett J, Nowak R, Sotirchos E, Longbrake E, Mace E, O'Connor K. A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases. The Journal Of Immunology 2024, 212: 785-800. PMID: 38251887, PMCID: PMC10932911, DOI: 10.4049/jimmunol.2300015.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderAb-dependent cellular cytotoxicityNK cellsMyasthenia gravisMG patientsInduced Ab-dependent cellular cytotoxicityNK cell-mediated effector functionsPeripheral blood immune cell populationsCell-mediated effector functionsNeuromyelitis optica spectrum disorder patientsBlood immune cell populationsAb-dependent cellular cytotoxicity activityNK marker CD56NK cell markersHLA-DR expressionNK cell subsetsExpression of perforinImmune cell populationsAutoimmune myasthenia gravisElevated disease burdenHLA-DRCell subsetsCellular cytotoxicityChemokine receptorsMultiparameter immunophenotyping
2023
Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis
Antozzi C, Guptill J, Bril V, Gamez J, Meuth S, Nowak R, Quan D, Sevilla T, Jouvin M, Jin J, Karcher K, Ramchandren S, Sun H, Ling L, Zhu Y, Arroyo S, Group F. Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis. Neurology 2023, 102: e207937. PMID: 38165333, PMCID: PMC10962909, DOI: 10.1212/wnl.0000000000207937.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsGeneralized myasthenia gravisSignificant dose responseAdverse eventsMG-ADLDay 57Myasthenia gravisDose responseMyasthenia Gravis ActivitiesPrimary safety endpointPrimary efficacy endpointSerious adverse eventsPhase 2 studyReceptor monoclonal antibodyDaily living (IADL) total scoreClinical trial registrationMG-ADL scoreDose-dependent reductionEudraCT numberQ2W groupEfficacy endpointPlacebo groupSafety endpointCare therapyReceptor autoantibodiesSubcutaneous batoclimab in generalized myasthenia gravis: Results from a Phase 2a trial with an open‐label extension
Nowak R, Breiner A, Bril V, Allen J, Khan S, Levine T, Jacobs D, Sahagian G, Siddiqi Z, Xu J, Macias W, Benatar M, Adams L, Genge A, Habib A, Hinton J, Holmlund T, Jacobs D, Lange D, Nicolle M, Phan H, Silvestri N, Small G, Yegiaian S. Subcutaneous batoclimab in generalized myasthenia gravis: Results from a Phase 2a trial with an open‐label extension. Annals Of Clinical And Translational Neurology 2023, 11: 194-206. PMID: 38062618, PMCID: PMC10791011, DOI: 10.1002/acn3.51946.Peer-Reviewed Original ResearchAnti-acetylcholine receptor antibodiesGeneralized myasthenia gravisTotal immunoglobulin GMyasthenia gravisImmunoglobulin G subclassesReceptor antibodiesOpen-label extension studyG subclassesImmunoglobulin GMyasthenia Gravis ActivitiesPatient-administered therapyPreliminary clinical benefitsQuantitative Myasthenia GravisOpen-label extensionPlacebo-controlled trialPhase 2a trialWeekly subcutaneous injectionsReceptor monoclonal antibodyMyasthenia Gravis QualityStudy support further investigationSupport further investigationMyasthenia Gravis CompositeEligible patientsPrimary endpointSecondary endpointsChange in concomitant therapies for generalized myasthenia gravis in patients receiving eculizumab: A retrospective analysis of registry data
Pulley M, Macwan S, Nowak R, Mozaffar T, Rodrigues E, Korideck H, Werneburg B, Narayanaswami P. Change in concomitant therapies for generalized myasthenia gravis in patients receiving eculizumab: A retrospective analysis of registry data. Journal Of The Neurological Sciences 2023, 455: 121092. DOI: 10.1016/j.jns.2023.121092.Peer-Reviewed Original ResearchRemission of severe myasthenia gravis after autologous stem cell transplantation
Schlatter M, Yandamuri S, O'Connor K, Nowak R, Pham M, Obaid A, Redman C, Provost M, McSweeney P, Pearlman M, Tees M, Bowen J, Nash R, Georges G. Remission of severe myasthenia gravis after autologous stem cell transplantation. Annals Of Clinical And Translational Neurology 2023, 10: 2105-2113. PMID: 37726935, PMCID: PMC10646993, DOI: 10.1002/acn3.51898.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationRefractory myasthenia gravisAutologous hematopoietic cell transplantationMyasthenia gravisCell transplantationAcetylcholine receptorsAutologous stem cell transplantationPhase 2 clinical trialAmerica (MGFA) clinical classificationMultiple immunomodulatory agentsRabbit antithymocyte globulinSevere myasthenia gravisAutoimmune neurological disordersHigh-dose chemotherapyMyasthenia Gravis FoundationNeuromuscular junction disordersStem cell transplantationTherapeutic plasma exchangeImmune cell subtypesDays of treatmentEffect of treatmentAntithymocyte globulinDisease activityComplete responseUnderwent treatmentLeg MRI as a Complementary Diagnostic Tool in the Assessment of Foot Drop
Torabi T, Zubair A, Nowak R, Tseng B, Haims A, Roy B. Leg MRI as a Complementary Diagnostic Tool in the Assessment of Foot Drop. Journal Of Clinical Neuromuscular Disease 2023, 25: 57-58. PMID: 37611274, DOI: 10.1097/cnd.0000000000000433.Peer-Reviewed Original ResearchPlasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions
Zubair A, Rethana M, Ma A, McAlpine L, Abulaban A, Munro B, Patwa H, Nowak R, Roy B. Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions. Journal Of Clinical Neuromuscular Disease 2023, 25: 11-17. PMID: 37611265, DOI: 10.1097/cnd.0000000000000439.Peer-Reviewed Original ResearchConceptsNeuro-immunological diseaseIntravenous immunoglobulinAutoimmune neurological disordersAutoimmune neuromuscular disorderAdult patientsElderly patientsNeurological disordersNeuromuscular disordersChronic inflammatory demyelinating polyradiculoneuropathyNational Inpatient Sample databaseNational Inpatient Sample datasetInflammatory demyelinating polyradiculoneuropathySafe therapeutic choiceRetrospective chart reviewAppropriate clinical settingSide effect profileDemyelinating polyradiculoneuropathyIVIG useChart reviewYounger patientsMyasthenia gravisEffect profileMedical historyPrimary diagnosisTherapeutic choiceIndividual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology
Pham M, Masi G, Patzina R, Obaid A, Oxendine S, Oh S, Payne A, Nowak R, O’Connor K. Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology. Acta Neuropathologica 2023, 146: 319-336. PMID: 37344701, PMCID: PMC11380498, DOI: 10.1007/s00401-023-02603-y.Peer-Reviewed Original ResearchConceptsMyasthenia gravisAntigenic modulationPathogenic mechanismsAutoimmune myasthenia gravisCurrent therapeutic approachesΑ-bungarotoxin bindingNicotinic acetylcholine receptorsReceptor blockadeSerum autoantibodiesAutoreactive clonesMonoclonal levelTherapeutic approachesMonoclonal autoantibodiesAcetylcholine receptorsComplement activationAutoantibodiesAChR subunitsJurkat cell lineDistinct molecular mechanismsPathogenic profilePathogenic capacityPathologyCell-based assaysMAbsPatientsMOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity
Yandamuri S, Filipek B, Obaid A, Lele N, Thurman J, Makhani N, Nowak R, Guo Y, Lucchinetti C, Flanagan E, Longbrake E, O’Connor K. MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity. JCI Insight 2023, 8: e165373. PMID: 37097758, PMCID: PMC10393237, DOI: 10.1172/jci.insight.165373.Peer-Reviewed Original ResearchConceptsMyelin oligodendrocyte glycoprotein antibody-associated diseaseAntibody-dependent cellular phagocytosisAntibody-dependent cellular cytotoxicityComplement-dependent cytotoxicityMOG autoantibodiesPatient seraCellular cytotoxicityEffector functionsComplement activityAntibody-associated diseaseMultiple mechanismsNK cellsPatient autoantibodiesCytotoxic capacityLesion histologyCellular phagocytosisFuture relapseIgG subclassesCerebrospinal fluidAutoantibodiesCNS conditionsMOGSerumRelapseCytotoxicityThe Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties
Jiang R, Roy B, Wu Q, Mohanty S, Nowak R, Shaw A, Kleinstein S, O’Connor K. The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties. ImmunoHorizons 2023, 7: 310-322. PMID: 37171806, PMCID: PMC10579972, DOI: 10.4049/immunohorizons.2200078.Peer-Reviewed Original ResearchConceptsInclusion body myositisMemory B cellsCell infiltrateBody myositisB cellsIBM muscle biopsiesB-cell infiltratesPlasma cell infiltrateClass-switched IgGMuscle tissueAdaptive immune receptor repertoire sequencingHumoral responseHealthy controlsIgA isotypePlasma cellsCell repertoireMuscle biopsyInfiltratesDegenerative disordersDisease pathologyRepertoire sequencingSkeletal muscleDermatomyositisPolymyositisMyositisInvestigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005)
Masi G, Pham M, Dai Y, Li Y, Karatz T, Oxendine S, Juel V, Ring A, Nowak R, Guptill J, O’Connor K. Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000202639.Peer-Reviewed Original ResearchChange in Concomitant Therapies for Generalized Myasthenia Gravis in Patients Receiving Eculizumab: a Retrospective Analysis of Registry Data (P1-5.002)
Pulley M, Macwan S, Nowak R, Mozaffar T, Rodrigues E, Korideck H, Werneburg B, Narayanaswami P. Change in Concomitant Therapies for Generalized Myasthenia Gravis in Patients Receiving Eculizumab: a Retrospective Analysis of Registry Data (P1-5.002). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000202372.Peer-Reviewed Original ResearchEarly B cell tolerance defects in anti-neurofascin 155 mediated chronic inflammatory demyelinating polyneuropathy (S40.005)
Roy B, Obaid A, Ohashi S, Coppola C, Das S, Hernandez A, Masi G, Martin-Aguilar L, Lleixà M, Nowak R, Querol Gutierrez L, O’Connor K. Early B cell tolerance defects in anti-neurofascin 155 mediated chronic inflammatory demyelinating polyneuropathy (S40.005). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000203364.Peer-Reviewed Original Research