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First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency

      Highlights

      • First-line immunotherapies of AE include IVMP, IVIG, and PE.
      • The combination of IVMP and IVIG was used most frequently than either alone.
      • A similar effectiveness was achieved with IVMP and IVIG either in combination or alone.
      • Monotherapy of IVMP might be a better choice with a better cost-efficiency.

      Abstract

      Objective

      To evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China.

      Methods

      Our study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency.

      Results

      Among the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP.

      Conclusion

      The combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.

      Keywords

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      References

        • Abboud H.
        • Probasco J.C.
        • Irani S.
        • Ances B.
        • Benavides D.R.
        • Bradshaw M.
        • Christo P.P.
        • Dale R.C.
        • Fernandez-Fournier M.
        • Flanagan E.P.
        • Gadoth A.
        • George P.
        • Grebenciucova E.
        • Jammoul A.
        • Lee S.T.
        • Li Y.
        • Matiello M.
        • Morse A.M.
        • Rae-Grant A.
        • Rojas G.
        • Rossman I.
        • Schmitt S.
        • Venkatesan A.
        • Vernino S.
        • Pittock S.J.
        • Titulaer M.J.
        • Autoimmune Encephalitis Alliance Clinicians N.
        Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.
        J. Neurol. Neurosurg. Psychiatry. 2021; 92: 757-768https://doi.org/10.1136/jnnp-2020-325300
        • Cohen J.
        • Sotoca J.
        • Gandhi S.
        • Yeshokumar A.K.
        • Gordon-Lipkin E.
        • Geocadin R.G.
        • Frick K.D.
        • Probasco J.C.
        • Venkatesan A.
        Autoimmune encephalitis: a costly condition.
        Neurology. 2019; 92: e964-e972https://doi.org/10.1212/WNL.0000000000006990
        • Cortese I.
        • Chaudhry V.
        • So Y.T.
        • Cantor F.
        • Cornblath D.R.
        • Rae-Grant A.
        Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the therapeutics and technology assessment subcommittee of the american academy of neurology.
        Neurology. 2011; 76: 294-300https://doi.org/10.1212/WNL.0b013e318207b1f6
        • Crowe E.P.
        • DeSimone R.A.
        Transfusion support and alternatives for Jehovah's Witness patients.
        Curr. Opin. Hematol. 2019; 26: 473-479https://doi.org/10.1097/MOH.0000000000000535
        • Fernandez-Zarzoso M.
        • Gomez-Segui I.
        • de la Rubia J.
        Therapeutic plasma exchange: review of current indications.
        Transfus Apher Sci. 2019; 58: 247-253https://doi.org/10.1016/j.transci.2019.04.007
        • Gong X.
        • Chen C.
        • Liu X.
        • Lin J.
        • Li A.
        • Guo K.
        • Zhou D.
        • Hong Z.
        Long-term functional outcomes and relapse of anti-NMDA receptor encephalitis: a cohort study in western China.
        Neurol. Neuroimmunol. Neuroinflamm. 2021; 8: e958https://doi.org/10.1212/NXI.0000000000000958
        • Graus F.
        • Cordon-Cardo C.
        • Posner J.B.
        Neuronal antinuclear antibody in sensory neuronopathy from lung cancer.
        Neurology. 1985; 35: 538-543https://doi.org/10.1212/wnl.35.4.538
        • Graus F.
        • Titulaer M.J.
        • Balu R.
        • Benseler S.
        • Bien C.G.
        • Cellucci T.
        • Cortese I.
        • Dale R.C.
        • Gelfand J.M.
        • Geschwind M.
        • Glaser C.A.
        • Honnorat J.
        • Hoftberger R.
        • Iizuka T.
        • Irani S.R.
        • Lancaster E.
        • Leypoldt F.
        • Pruss H.
        • Rae-Grant A.
        • Reindl M.
        • Rosenfeld M.R.
        • Rostasy K.
        • Saiz A.
        • Venkatesan A.
        • Vincent A.
        • Wandinger K.P.
        • Waters P.
        • Dalmau J.
        A clinical approach to diagnosis of autoimmune encephalitis.
        Lancet Neurol. 2016; 15: 391-404https://doi.org/10.1016/S1474-4422(15)00401-9
        • Guo Y.
        • Tian X.
        • Wang X.
        • Xiao Z.
        Adverse effects of immunoglobulin therapy.
        Front. Immunol. 2018; 9: 1299https://doi.org/10.3389/fimmu.2018.01299
        • Heine J.
        • Ly L.T.
        • Lieker I.
        • Slowinski T.
        • Finke C.
        • Pruss H.
        • Harms L.
        Immunoadsorption or plasma exchange in the treatment of autoimmune encephalitis: a pilot study.
        J. Neurol. 2016; 263: 2395-2402https://doi.org/10.1007/s00415-016-8277-y
        • Jiang Y.
        • Tian X.
        • Gu Y.
        • Li F.
        • Wang X.
        Application of plasma exchange in steroid-responsive encephalopathy.
        Front. Immunol. 2019; 10: 324https://doi.org/10.3389/fimmu.2019.00324
        • Lancaster E.
        The diagnosis and treatment of autoimmune encephalitis.
        J. Clin. Neurol. 2016; 12: 1-13https://doi.org/10.3988/jcn.2016.12.1.1
        • Lennon V.A.
        • Wingerchuk D.M.
        • Kryzer T.J.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Fujihara K.
        • Nakashima I.
        • Weinshenker B.G.
        A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.
        Lancet. 2004; 364: 2106-2112https://doi.org/10.1016/S0140-6736(04)17551-X
        • Li A.
        • Gong X.
        • Guo K.
        • Lin J.
        • Zhou D.
        • Hong Z.
        Direct economic burden of patients with autoimmune encephalitis in western China.
        Neurol. Neuroimmunol. Neuroinflamm. 2020; 7: e891https://doi.org/10.1212/NXI.0000000000000891
        • Liu D.
        • Ahmet A.
        • Ward L.
        • Krishnamoorthy P.
        • Mandelcorn E.D.
        • Leigh R.
        • Brown J.P.
        • Cohen A.
        • Kim H.
        A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy.
        Allergy Asthma Clin. Immunol. 2013; 9: 30https://doi.org/10.1186/1710-1492-9-30
        • Lunemann J.D.
        • Nimmerjahn F.
        • Dalakas M.C.
        Intravenous immunoglobulin in neurology-mode of action and clinical efficacy.
        Nat. Rev. Neurol. 2015; 11: 80-89https://doi.org/10.1038/nrneurol.2014.253
        • Lunemann J.D.
        • Quast I.
        • Dalakas M.C.
        Efficacy of intravenous immunoglobulin in neurological diseases.
        Neurotherapeutics. 2016; 13: 34-46https://doi.org/10.1007/s13311-015-0391-5
        • McKeon A.
        • Zekeridou A.
        Autoimmune encephalitis management: MS centers and beyond.
        Mult. Scler. 2020; 26: 1618-1626https://doi.org/10.1177/1352458520905485
        • Osman C.
        • Jennings R.
        • El-Ghariani K.
        • Pinto A.
        Plasma exchange in neurological disease.
        Pract. Neurol. 2020; 20: 92-99https://doi.org/10.1136/practneurol-2019-002336
        • Qiao S.
        • Wu H.K.
        • Liu L.L.
        • Zhang R.R.
        • Wang M.L.
        • Han T.
        • Zhang S.C.
        • Liu X.W.
        Characteristics and prognosis of autoimmune encephalitis in the east of China: a multi-center study.
        Front. Neurol. 2021; 12642078https://doi.org/10.3389/fneur.2021.642078
        • Ramanathan S.
        • Al-Diwani A.
        • Waters P.
        • Irani S.R.
        The autoantibody-mediated encephalitides: from clinical observations to molecular pathogenesis.
        J. Neurol. 2021; 268: 1689-1707https://doi.org/10.1007/s00415-019-09590-9
        • Ross E.L.
        • Becker J.E.
        • Linnoila J.J.
        • Soeteman D.I.
        Cost-effectiveness of routine screening for autoimmune encephalitis in patients with first-episode psychosis in the United States.
        J. Clin. Psychiatry. 2020; 82 (19m13168)https://doi.org/10.4088/JCP.19m13168
        • Scharman C.D.
        • Burger D.
        • Shatzel J.J.
        • Kim E.
        • DeLoughery T.G.
        Treatment of individuals who cannot receive blood products for religious or other reasons.
        Am. J. Hematol. 2017; 92: 1370-1381https://doi.org/10.1002/ajh.24889
        • Shan W.
        • Yang H.
        • Wang Q.
        Neuronal surface antibody-medicated autoimmune encephalitis (Limbic Encephalitis) in China: a multiple-center, retrospective study.
        Front. Immunol. 2021; 12621599https://doi.org/10.3389/fimmu.2021.621599
        • Titulaer M.J.
        • McCracken L.
        • Gabilondo I.
        • Armangue T.
        • Glaser C.
        • Iizuka T.
        • Honig L.S.
        • Benseler S.M.
        • Kawachi I.
        • Martinez-Hernandez E.
        • Aguilar E.
        • Gresa-Arribas N.
        • Ryan-Florance N.
        • Torrents A.
        • Saiz A.
        • Rosenfeld M.R.
        • Balice-Gordon R.
        • Graus F.
        • Dalmau J.
        Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study.
        Lancet Neurol. 2013; 12: 157-165https://doi.org/10.1016/S1474-4422(12)70310-1
        • Vincent A.
        • Buckley C.
        • Schott J.M.
        • Baker I.
        • Dewar B.K.
        • Detert N.
        • Clover L.
        • Parkinson A.
        • Bien C.G.
        • Omer S.
        • Lang B.
        • Rossor M.N.
        • Palace J.
        Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis.
        Brain. 2004; 127 (Pt 3): 701-712https://doi.org/10.1093/brain/awh077
        • Viswanathan S.
        • Appiwatanakul M.
        • Nayak A.
        • Islam B.
        • Khatri B.
        • Pangeran D.
        • Bambardekar H.
        • Maharani K.
        • Tan K.
        • Alexander M.
        • Hussain M.E.
        • Adenan M.S.
        • Danapaul N.A.
        • Khalife N.
        • Ohnmar O.
        • Ong B.H.
        • Estiasari R.
        • Hanifa S.N.
        • Siritho S.
        • Ng C.F.
        • Ratna S.
        • Umapathi T.
        • Thit W.M.
        • Ramli Y.
        • Lee Y.Y.
        • Hiew F.L.
        Proceedings of the inaugural strategy meeting for the establishment of a Southeast Asia regional therapeutic plasma exchange consortium for neurological disorders.
        Ther. Apher. Dial. 2019; 23: 289-297https://doi.org/10.1111/1744-9987.12806
        • Xu X.
        • Lu Q.
        • Huang Y.
        • Fan S.
        • Zhou L.
        • Yuan J.
        • Yang X.
        • Ren H.
        • Sun D.
        • Dai Y.
        • Zhu H.
        • Jiang Y.
        • Zhu Y.
        • Peng B.
        • Cui L.
        • Guan H.
        Anti-NMDAR encephalitis: a single-center, longitudinal study in China.
        Neurol. Neuroimmunol. Neuroinflamm. 2020; 7: e633https://doi.org/10.1212/NXI.0000000000000633
        • Yasir M.
        • Goyal A.
        • Bansal P.
        • Sonthalia S.
        Corticosteroid Adverse Effects.
        StatPearls, Treasure Island (FL)2021
        • Zhang Y.
        • Huang H.J.
        • Chen W.B.
        • Liu G.
        • Liu F.
        • Su Y.Y.
        Clinical efficacy of plasma exchange in patients with autoimmune encephalitis.
        Ann. Clin. Transl. Neurol. 2021; 8: 763-773https://doi.org/10.1002/acn3.51313
        • Zuliani L.
        • Nosadini M.
        • Gastaldi M.
        • Spatola M.
        • Iorio R.
        • Zoccarato M.
        • Mariotto S.
        • De Gaspari P.
        • Perini F.
        • Ferrari S.
        • Evoli A.
        • Sartori S.
        • Franciotta D.
        • Giometto B.
        Management of antibody-mediated autoimmune encephalitis in adults and children: literature review and consensus-based practical recommendations.
        Neurol. Sci. 2019; 40: 2017-2030https://doi.org/10.1007/s10072-019-03930-3