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 administrationUnited 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 expressionA 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 treatmentPlasmapheresis 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 assaysMAbsPatientsChange 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 ResearchClinicoserological insights into patients with immune checkpoint inhibitor‐induced myasthenia gravis
Masi G, Pham M, Karatz T, Oh S, Payne A, Nowak R, Howard J, Guptill J, Juel V, O'Connor K. Clinicoserological insights into patients with immune checkpoint inhibitor‐induced myasthenia gravis. Annals Of Clinical And Translational Neurology 2023, 10: 825-831. PMID: 36924454, PMCID: PMC10187728, DOI: 10.1002/acn3.51761.Peer-Reviewed Original Research
2022
Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy
Fichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O’Connor K. Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy. Acta Neuropathologica Communications 2022, 10: 154. PMID: 36307868, PMCID: PMC9617453, DOI: 10.1186/s40478-022-01454-0.Peer-Reviewed Original ResearchConceptsB cell depletion therapyB cell clonesMuSK-MG patientsMyasthenia gravisB cellsMG patientsDepletion therapyCell clonesAutoantibody-producing B cellsMuscle-specific tyrosine kinaseComplete stable remissionB cell receptor repertoireCell receptor repertoireValuable candidate biomarkersB cell receptorMG relapseClinical relapseStable remissionDisease relapseAutoimmune disordersRelapsePatientsAcetylcholine receptorsCandidate biomarkersReceptor repertoireMyasthenia Gravis in the Setting of Immune Checkpoint Inhibitor Therapy: Practical Considerations and Opinion-Based Approach to Acute Management
Zubair A, Roy B, Baehring J, Nowak R. Myasthenia Gravis in the Setting of Immune Checkpoint Inhibitor Therapy: Practical Considerations and Opinion-Based Approach to Acute Management. Cureus 2022, 14: e30638. PMID: 36439604, PMCID: PMC9683636, DOI: 10.7759/cureus.30638.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsCheckpoint inhibitor therapyMyasthenia gravisCheckpoint inhibitorsInhibitor therapyICI therapyImmune checkpoint inhibitor therapyImmune checkpoint inhibitor useInflammatory adverse effectsBest treatment algorithmCell lung cancerCheckpoint inhibitor useRenal cell cancerSystem side effectsPotential treatment optionNeurologic complicationsInhibitor useAcute managementOncologic treatmentAnti-CTLA4Cell cancerClinical outcomesTreatment algorithmClinical manifestationsTreatment optionsReal-world experience of eculizumab treatment for generalized myasthenia gravis: initial data from a registry of patients with generalized myasthenia gravis in the USA (S25.006)
Narayanaswami P, Cutter G, Nowak R, Greene E, Muppidi S, Mozaffar T, Rodrigues E, Korideck H, Howard J. Real-world experience of eculizumab treatment for generalized myasthenia gravis: initial data from a registry of patients with generalized myasthenia gravis in the USA (S25.006). Neurology 2022, 98 DOI: 10.1212/wnl.98.18_supplement.1320.Peer-Reviewed Original ResearchA prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2) (P6-13.005)
Guptill J, Nowak R, Guidon A, Howard J, Soliven B, Hammett A, Sheldon B, Li Y, Meece T, Aban I, Cutter G, Kaminski H. A prospective natural history study and biorepository for patients with myasthenia gravis (EXPLORE-MG2) (P6-13.005). Neurology 2022, 98 DOI: 10.1212/wnl.98.18_supplement.2269.Peer-Reviewed Original Research
2021
Topline Results of a Phase 2 Study of Subcutaneous IMVT-1401 in Patients with Generalized Myasthenia Gravis (1417)
Benatar M, Breiner A, Bril V, Nowak R, Dunn I, Jacobs A. Topline Results of a Phase 2 Study of Subcutaneous IMVT-1401 in Patients with Generalized Myasthenia Gravis (1417). Neurology 2021, 96 DOI: 10.1212/wnl.96.15_supplement.1417.Peer-Reviewed Original ResearchVivacity-MG: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Nipocalimab Administered to Adults with Generalized Myasthenia Gravis (2157)
Guptill J, Antozzi C, Bril V, Gamez J, Meuth S, Blanco J, Nowak R, Quan D, Sevilla T, Szczudlik A, Hegarty B, Jouvin M, Jin J, Arroyo S. Vivacity-MG: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Nipocalimab Administered to Adults with Generalized Myasthenia Gravis (2157). Neurology 2021, 96 DOI: 10.1212/wnl.96.15_supplement.2157.Peer-Reviewed Original Research
2020
Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis
Howard JF, Nowak RJ, Wolfe GI, Freimer ML, Vu TH, Hinton JL, Benatar M, Duda PW, MacDougall JE, Farzaneh-Far R, Kaminski HJ, Barohn R, Dimachkie M, Pasnoor M, Farmakidis C, Liu T, Colgan S, Benatar M, Bertorini T, Pillai R, Henegar R, Bromberg M, Gibson S, Janecki T, Freimer M, Elsheikh B, Matisak P, Genge A, Guidon A, David W, Habib A, Mathew V, Mozaffar T, Hinton J, Hewitt W, Barnett D, Sullivan P, Ho D, Howard J, Traub R, Chopra M, Kaminski H, Aly R, Bayat E, Abu-Rub M, Khan S, Lange D, Holzberg S, Khatri B, Lindman E, Olapo T, Sershon L, Lisak R, Bernitsas E, Jia K, Malik R, Lewis-Collins T, Nicolle M, Nowak R, Sharma A, Roy B, Nye J, Pulley M, Berger A, Shabbir Y, Sachdev A, Patterson K, Siddiqi Z, Sivak M, Bratton J, Small G, Kohli A, Fetter M, Vu T, Lam L, Harvey B, Wolfe G, Silvestri N, Patrick K, Zakalik K, Duda P, MacDougall J, Farzaneh-Far R, Pontius A, Hoarty M. Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis. JAMA Neurology 2020, 77: 582-592. PMID: 32065623, PMCID: PMC7042797, DOI: 10.1001/jamaneurol.2019.5125.Peer-Reviewed Original ResearchConceptsGeneralized myasthenia gravisSecondary end pointsDaily living scoreTolerability profileEnd pointLiving scoreMyasthenia gravisClinical effectsPlacebo-controlled phase 2 clinical trialKey secondary efficacy end pointsKey secondary end pointSecondary efficacy end pointsSevere Generalized Myasthenia GravisQuantitative Myasthenia Gravis ScorePhase 2 clinical trialAcetylcholine receptor autoantibodiesEfficacy end pointMyasthenia gravis scoreMG activityComplement component 5Disease-specific variablesQuality of lifeComplete complement inhibitionBroader populationDaily SCMonovalent IgG4 autoantibodies require self-antigen driven affinity maturation to acquire pathogenic capacity
Fichtner M, Vieni C, Redler R, Jiang R, Suarez P, Nowak R, Burden S, Bhabha G, Ekiert D, O’Connor K. Monovalent IgG4 autoantibodies require self-antigen driven affinity maturation to acquire pathogenic capacity. The Journal Of Immunology 2020, 204: 224.39-224.39. DOI: 10.4049/jimmunol.204.supp.224.39.Peer-Reviewed Original ResearchMuSK myasthenia gravisMyasthenia gravisUnmutated common ancestorPathogenic capacityB-cell-mediated autoimmune diseasesAntigen-driven affinity maturationCell-mediated autoimmune diseaseMuscle-specific tyrosine kinaseSubset of patientsAutoreactive B cellsMonovalent antigen-binding fragmentsAffinity maturationHuman monoclonal autoantibodiesUnique autoantibodiesIgG4 autoantibodiesPathogenic autoantibodiesAutoimmune disordersAutoimmune responseAutoimmune diseasesSelf antigensIgG4 subclassAutoantibodiesMG autoantibodiesB cellsFab-arm exchangeGuidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic
Group I, Jacob S, Muppidi S, Guidon A, Guptill J, Hehir M, Howard J, Illa I, Mantegazza R, Murai H, Utsugisawa K, Vissing J, Wiendl H, Nowak R. Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic. Journal Of The Neurological Sciences 2020, 412: 116803. PMID: 32247193, PMCID: PMC7105910, DOI: 10.1016/j.jns.2020.116803.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusClinical Trials as TopicCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentDisease ManagementDisease SusceptibilityHumansImmunoglobulins, IntravenousImmunologic FactorsImmunosuppressive AgentsImmunotherapyLambert-Eaton Myasthenic SyndromeMyasthenia GravisPandemicsPlasma ExchangePneumonia, ViralSARS-CoV-2Vaccines