Abstract
Chronic immune-mediated neuropathies, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), neuropathies associated with monoclonal gammopathy, and multifocal motor neuropathy (MMN), are a group of disorders deemed to be caused by an immune response against peripheral nerve antigens. Several immune therapies have been reported to be variably effective in these neuropathies including steroids, plasma exchange, and high-dose intravenous (IVIg) or subcutaneous (SCIg) immunoglobulins. These therapies are however far from being invariably effective and may be associated with a number of side effects leading to the use of immunosuppressive agents whose efficacy has not been so far confirmed in randomized trials. More recently, new biological agents, such as rituximab, have proved to be effective in patients with neuropathy associated with IgM monoclonal gammopathy and are currently tested in CIDP.
Similar content being viewed by others
References
Lehmann HC, Broke N, Kuwabara S (2019) Chronic inflammatory demyelinating polyneuropathy: update on diagnosis, immunopathogenesis and treatment. J Neurol Neurosurg Psychiatry 90:981–987
Oaklander AL, Lunn MP, Hughes RA et al (2017) Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews. Cochrane Database Syst Rev 1:CD010369
Hughes RA, Mehndiratta MM, Rajabally YA (2017) Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev 11:CD002062
Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society-first revision. J Peripher Nerv Syst 15:1–9
Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, van Doorn P, ICE Study Group (2008) Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol 7:136–144
Kuwabara S, Mori M, Misawa S, Suzuki M, Nishiyama K, Mutoh T, Doi S, Kokubun N, Kamijo M, Yoshikawa H, Abe K, Nishida Y, Okada K, Sekiguchi K, Sakamoto K, Kusunoki S, Sobue G, Kaji R, Glovenin-I CIDP Study Group (2017) Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial. J Neurol Neurosurg Psychiatry 88:832–838
Kuitwaard K, Brusse E, Jacobs BC, Vrancken AFJE, Eftimov F, Notermans NC, Kooi AJ, Fokkink WJR, Nieboer D, Lingsma HF, Merkies ISJ, Doorn PA (2020) Randomised trial of intravenous immunoglobulin maintenance treatment regimens in chronic inflammatory demyelinating polradiculoneuropathy. Eur J Neurol. https://doi.org/10.1111/ene.14501
Eftimov F, Winer JB, Vermeulen M, de Haan R, van Schaik IN (2013) Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev 12:CD001797
Lewis RA, Cornblath DR, Hartung HP, Sobue G, Lawo JP, Mielke O, Durn BL, Bril V, Merkies ISJ, Bassett P, Cleasby A, Schaik IN, PATH study group, Sabet A, George K, Roberts L, Carne R, Blum S, Henderson R, van Damme P, Demeestere J, Larue S, D’Amour C, Kunc P, Valis M, Sussova J, Kalous T, Talab R, Bednar M, Toomsoo T, Rubanovits I, Gross-Paju K, Sorro U, Saarela M, Auranen M, Pouget J, Attarian S, le Masson G, Wielanek A, Desnuelle C, Delmon E, Clavelou P, Aufauvre D, Schmidt J, Zschuentzsch J, Sommer C, Kramer D, Hoffmann O, Goerlitz C, Haas J, Chatzopoulos M, Yoon R, Gold R, Berlit P, Jaspert-Grehl A, Liebetanz D, Kutschenko A, Stangel M, Trebst C, Baum P, Bergh F, Klehmet J, Meisel A, Klostermann F, Oechtering J, Lehmann H, Schroeter M, Hagenacker T, Mueller D, Sperfeld A, Bethke F, Drory IV, Algom A, Yarnitsky D, Murinson B, di Muzio A, Ciccocioppo F, Sorbi S, Mata S, Schenone A, Grandis M, Lauria G, Cazzato D, Antonini G, Morino S, Cocito D, Zibetti M, Yokota T, Ohkubo T, Kanda T, Kawai M, Kaida K, Onoue H, Kuwabara S, Mori M, Iijima M, Ohyama K, Baba M, Tomiyama M, Nishiyama K, Akutsu T, Yokoyama K, Kanai K, Schaik IN, Eftimov F, Notermans NC, Visser N, Faber C, Hoeijmakers J, Rejdak K, Chyrchel-Paszkiewicz U, Casanovas Pons C, Antonia M, Gamez J, Salvado M, Infante CM, Benitez S, Lunn M, Morrow J, Gosal D, Lavin T, Melamed I, Testori A, Ajroud-Driss S, Menichella D, Simpson E, Lai ECH, Dimachkie M, Barohn RJ, Beydoun S, Johl H, Lange D, Shtilbans A, Muley S, Ladha S, Freimer M, Kissel J, Latov N, Chin R, Ubogu E, Mumfrey S, Rao T, MacDonald P, Sharma K, Gonzalez G, Allen J, Walk D, Hobson-Webb L, Gable K (2020) Placebo effect in chronic inflammatory demyelinating polyneuropathy: the PATH study and a systematic review. J Peripher Nerv Syst 25:230–237
Adrichem ME, Eftimov F, van Schaik IN (2016) Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy, a time to start and a time to stop. J Peripher Nerv Syst 21:121–127
Doneddu PE, Mandia D, Gentile F, Gallia F, Liberatore G, Terenghi F, Ruiz M, Nobile-Orazio E (2020) Home monitoring of maintenance intravenous immunoglobulin therapy in patients with chronic inflammatory neuropathy. J Peripher Nerv Syst 25:238–246
Kuitwaard K, Fokkink WR, Brusse E et al (2017) Maintenance IV immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy. J Peripher Nerv Syst 22:425–432
Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM (2016) A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. J Peripher Nerv Syst 21:33–37
Mielke O, Bril V, Cornblath DR, Lawo JP, Geloven N, Hartung HP, Lewis RA, Merkies ISJ, Sobue G, Durn B, Shebl A, Schaik IN, on behalf of the PATH study group, Sabet A, George K, Roberts L, Carne R, Blum S, Henderson R, van Damme P, Demeestere J, Larue S, D’Amour C, Kunc P, Valis M, Sussova J, Kalous T, Talab R, Bednar M, Toomsoo T, Rubanovits I, Gross-Paju K, Sorro U, Saarela M, Auranen M, Pouget J, Attarian S, le Masson G, Wielanek-Bachelet A, Desnuelle C, Delmont E, Clavelou P, Aufauvre D, Schmidt J, Zschuentzsch J, Sommer C, Kramer D, Hoffmann O, Goerlitz C, Haas J, Chatzopoulos M, Yoon R, Gold R, Berlit P, Jaspert-Grehl A, Liebetanz D, Kutschenko A, Stangel M, Trebst C, Baum P, Bergh F, Klehmet J, Meisel A, Klostermann F, Oechtering J, Lehmann H, Schroeter M, Hagenacker T, Mueller D, Sperfeld A, Bethke F, Drory V, Algom A, Yarnitsky D, Murinson B, di Muzio A, Ciccocioppo F, Sorbi S, Mata S, Schenone A, Grandis M, Lauria G, Cazzato D, Antonini G, Morino S, Cocito D, Zibetti M, Yokota T, Ohkubo T, Kanda T, Kawai M, Kaida K, Onoue H, Kuwabara S, Mori M, Iijima M, Ohyama K, Baba M, Tomiyama M, Nishiyama K, Akutsu T, Yokoyama K, Kanai K, van Schaik IN, Eftimov F, Notermans NC, Visser N, Faber C, Hoeijmakers J, Rejdak K, Chyrchel-Paszkiewicz U, Casanovas Pons C, Antonia M, Gamez J, Salvado M, Infante CM, Benitez S, Lunn M, Morrow J, Gosal D, Lavin T, Melamed I, Testori A, Ajroud-Driss S, Menichella D, Simpson E, Lai ECH, Dimachkie M, Barohn RJ, Beydoun S, Johl H, Lange D, Shtilbans A, Muley S, Ladha S, Freimer M, Kissel J, Latov N, Chin R, Ubogu E, Mumfrey S, Rao T, MacDonald P, Sharma K, Gonzalez G, Allen J, Walk D, Hobson-Webb L, Gable K (2019) Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: results from the pre-randomization phase of the Polyneuropathy And Treatment with Hizentra study. J Peripher Nerv Syst 24:72–79
Kapoor M, Reilly MM, Manji H, Lunn MP, Aisling S., Carr (2020) Dramatic clinical response to ultra-high dose IVIg in otherwise treatment resistant inflammatory neuropathies. Int J Neurosci 1–10
Seino Y, Nakamura T, Hirohata M, Kawarabayashi T, Okushima T, Shoji M (2019) Severe chronic inflammatory demyelinating polyneuropathy ameliorated following high-dose (3 g/kg) intravenous immunoglobulin therapy. Intern Med 58:855–859
Vanhoutte EK, Faber CG, Merkies IS, PeriNomS study group (2013) 196th ENMC international workshop: outcome measures in inflammatory peripheral neuropathies 8-10 February 2013, Naarden, The Netherlands. Neuromuscul Disord 23:924–933
Draak TH, Vanhoutte EK, van Nes SI et al (2014) Changing outcome in inflammatory neuropathies: Rasch-comparative responsiveness. Neurology 83:2124–2132
Doneddu PE, Hadden RDM (2020) Daily grip strength response to intravenous immunoglobulin in chronic immune neuropathies. Muscle Nerve 62:103–110
Kapoor M, Spillane J, Englezou C, Sarri-Gonzalez S, Bell R, Rossor A, Manji H, Reilly MM, Lunn MP, Carr A (2020) Thromboembolic risk with IVIg: incidence and risk factors in patients with inflammatory neuropathy. Neurology 94:e635–e638
Van Schaik IN, Bril V, van Geloven N et al (2018) Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 17:35–46
van Schaik IN, Mielke O, Bril V, van Geloven N, Hartung HP, Lewis RA, Sobue G, Lawo JP, Praus M, Durn BL, Cornblath DR, Merkies ISJ, on behalf of the PATH study group (2019) Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP: PATH extension study. Neurol Neuroimmunol Neuroinflamm 6:e590
Berger M, Jolles S, Orange JS, Sleasman JW (2013) Bioavailability of IgG administered by the subcutaneous route. J Clin Immunol 33:984–990
Cocito D, Merola A, Peci E et al (2014) Subcutaneous immunoglobulin in CIDP and MMN: a short-term nationwide study. J Neurol 261:2159–2164
Cocito D, Merola A, Romagnolo A, Peci E, Toscano A, Mazzeo A, Gentile L, Russo M, Fazio R, Filosto M, Siciliano G, Schirinzi E, Nobile-Orazio E, Lopiano L (2016) Subcutaneous immunoglobulin in CIDP and MMN: a different long-term clinical response? J Neurol Neurosurg Psychiatry 87:791–793
Markvardsen LH, Harbo T, Sindrup SH, Christiansen I, Andersen H, Jakobsen J, The Danish CIDP and MMN Study Group (2014) Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy. Eur J Neurol 21:1465–1470
Cirillo G, Todisco V, Ricciardi D, Tedeschi G (2019) Clinical-neurophysiological correlations in chronic inflammatory demyelinating polyradiculoneuropathy patients treated with subcutaneous immunoglobulin. Muscle Nerve 60:662–667
Gentile L, Mazzeo A, Russo M, Arimatea I, Vita G, Toscano A (2020) Long-term treatment with subcutaneous immunoglobulin in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a follow-up period up to 7 years. Sci Rep 10:7910
Markvardsen LH, Debost J, Harbo T et al (2013) Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol 20:836–842
Cocito D, Serra G, Paolasso I, Barilà DA, Lopiano L, Cattel L (2012) Economic and quality of life evaluation of different modalities of immunoglobulin therapy in chronic dysimmune neuropathies. J Peripher Nerv Syst 17:426–428
Lazzaro C, Lopiano L, Cocito D (2014) Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis. Neurol Sci 35:1023–1034
Le Masson G, Solé G, Desnuelle C et al (2018) Home versus hospital immunoglobulin treatment for autoimmune neuropathies: a cost minimization analysis. Brain Behav 8:e00923
van Schaik IN, Eftimov F, van Doorn PA, Brusse E, van den Berg LH, van der Pol WL, Faber CG, van Oostrom JCH, Vogels OJM, Hadden RDM, Kleine BU, van Norden AGW, Verschuuren JJGM, Dijkgraaf MGW, Vermeulen M (2010) Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind randomised controlled trial. Lancet Neurol 9:245–253
Nobile-Orazio E, Cocito D, Jann S, Uncini A, Beghi E, Messina P, Antonini G, Fazio R, Gallia F, Schenone A, Francia A, Pareyson D, Santoro L, Tamburin S, Macchia R, Cavaletti G, Giannini F, Sabatelli M, IMC Trial Group (2012) Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial. Lancet Neurol 11:493–502
Nobile-Orazio E, Cocito D, Jann S, Uncini A, Messina P, Antonini G, Fazio R, Gallia F, Schenone A, Francia A, Pareyson D, Santoro L, Tamburin S, Cavaletti G, Giannini F, Sabatelli M, Beghi E (2015) Frequency and time to relapse after discontinuing 6-month therapy with IVIg or pulsed methylprednisolone in CIDP. J Neurol Neurosurg Psychiatry 86:729–734
Rabin M, Mutlu G, Stojkovic T et al (2014) Chronic inflammatory demyelinating polyradiculoneuropathy: search for factors associated with treatment dependence or successful withdrawal. J Neurol Neurosurg Psychiatry 85:899–904
Adrichem ME, Bus SR, Wieske L, Mohammed H, Verhamme C, Hadden R, Schaik IN, Eftimov F (2020) Combined intravenous immunoglobulin and methylprednisolone as induction treatment in chronic inflammatory demyelinating polyneuropathy (OPTIC protocol): a prospective pilot study. Eur J Neurol 27:506–513
Mahdi-Rogers M, Brassington R, Gunn AA et al (2017) Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev 5(5):CD003280
Hughes R, Dalakas MC, Merkies I et al (2018) Oral fingolimod for chronic inflammatory demyelinating polyradiculoneuropathy (FORCIDP trial): a double-blind, multicentre, randomised controlled trial. Lancet Neurol 17:933
Querol L, Rojas-García R, Diaz-Manera J, Barcena J, Pardo J, Ortega-Moreno A, Sedano MJ, Seró-Ballesteros L, Carvajal A, Ortiz N, Gallardo E, Illa I (2015) Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins. Neurol Neuroimmunol Neuroinflamm 2:e149
Jiao L, Xiang Y, Li S, Zhang F, Ruan X, Guo S (2020) Efficacy of low dose rituximab in treatment-resistant CIDP with antibodies against NF-155. J Neuroimmunol 345:577280
Benedetti L, Briani C, Franciotta D, Fazio R, Paolasso I, Comi C, Luigetti M, Sabatelli M, Giannini F, Mancardi GL, Schenone A, Nobile-Orazio E, Cocito D (2011) Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature. J Neurol Neurosurg Psychiatry 82:306–308
Roux T, Debs R, Maisonobe T, Lenglet T, Delorme C, Louapre C, Leblond V, Viala K (2018) Rituximab in chronic inflammatory demyelinating polyradiculoneuropathy with associated diseases. J Peripher Nerv Syst 23:235–240
Kilidireas C, Anagnostopoulos A, Karandreas N, Mouselimi L, Dimopoulos MA (2006) Rituximab therapy in monoclonal IgM-related neuropathies. Leuk Lymphoma 47:859–864
Muley SA, Jacobsen B, Parry G, Usman U, Ortega E, Walk D, Allen J, Pasnoor M, Varon M, Dimachkie MM (2020) Rituximab in refractory chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 61:575–579
Velardo D, Riva N, Del Carro U et al (2017) Rituximab in refractory chronic inflammatory demyelinating polyradiculoneuropathy: report of four cases. J Neurol 264:1011–1014
Latov N, Sherman WH, Nemni R, Galassi G, Shyong JS, Penn AS, Chess L, Olarte MR, Rowland LP, Osserman EF (1980) Plasma-cell dyscrasia and peripheral neuropathy with a monoclonal antibody to peripheral-nerve myelin. N Engl J Med 303:618–621
Briani C, Visentin A, Campagnolo M, Salvalaggio A, Ferrari S, Cavallaro T, Manara R, Gasparotti R, Piazza F (2019) Peripheral nervous system involvement in lymphomas. J Peripher Nerv Syst 24:5–18
Lunn MP, Nobile-Orazio E (2016) Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database Syst Rev 10:CD002827
Nobile-Orazio E, Meucci N, Baldini L et al (2000) Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain 123(Pt 4):710–717
Pestronk A, Florence J, Miller T, Choksi R, al-Lozi MT, Levine TD (2003) Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry 74:485–489
Renaud S, Gregor M, Fuhr P, Lorenz D, Deuschl G, Gratwohl A, Steck AJ (2003) Rituximab in the treatment of polyneuropathy associated with anti-MAG antibodies. Muscle Nerve 27:611–615
Renaud S, Fuhr P, Gregor M, Schweikert K, Lorenz D, Daniels C, Deuschl G, Gratwohl A, Steck AJ (2006) High-dose rituximab and anti-MAG-associated polyneuropathy. Neurology 66:742–744
Benedetti L, Briani C, Grandis M, Vigo T, Gobbi M, Ghiglione E, Carpo M, Cocito D, Caporale CM, Sormani MP, Mancardi GL, Nobile-Orazio E, Schenone A (2007) Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M. J Peripher Nerv Syst 12:102–107
Benedetti L, Briani C, Franciotta D, Carpo M, Padua L, Zara G, Zambello R, Sormani MP, Mancardi GL, Nobile-Orazio E, Schenone A (2008) Long-term effect of rituximab in anti-MAG polyneuropathy. Neurology 71:1742–1744
Niermeijer JM, Eurelings M, Lokhorst HL et al (2009) Rituximab for polyneuropathy with IgM monoclonal gammopathy. J Neurol Neurosurg Psychiatry 80:1036–1039
Dalakas MC, Rakocevic G, Salajegheh M, Dambrosia JM, Hahn AF, Raju R, McElroy B (2009) Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann Neurol 65:286–293
Leger JM, Viala K, Nicolas G, Creange A, Vallat JM, Pouget J, Clavelou P, Vial C, Steck A, Musset L, Marin B, For the RIMAG Study Group (France and Switzerland) (2013) Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. Neurology 80:2217–2225
Iancu Ferfoglia R, Guimarães-Costa R, Viala K, Musset L, Neil J, Marin B, Léger JM (2016) Long-term efficacy of rituximab in IgM anti-myelin-associated glycoprotein neuropathy: RIMAG follow-up study. J Peripher Nerv Syst 21:10–14
Campagnolo M, Zambello R, Nobile-Orazio E, Benedetti L, Marfia GA, Riva N, Castellani F, Bianco M, Salvalaggio A, Garnero M, Ruiz M, Mataluni G, Fazio R, Ermani M, Briani C (2017) IgM MGUS and Waldenstrom-associated anti-MAG neuropathies display similar response to rituximab therapy. J Neurol Neurosurg Psychiatry 88:1094–1097
Colchester NTH, Allen D, Katifi HA et al (2020) Chemoimmunotherapy with rituximab, cyclophosphamide and prednisolone in IgM paraproteinaemic neuropathy: evidence of sustained improvement in electrophysiological, serological and functional outcomes [Haematologica published online ahead of print, 2020 Apr 30]
Massa F, Zuppa A, Pesce G, Demichelis C, Bergamaschi M, Garnero M, Briani C, Ferrari S, Schenone A, Benedetti L (2020) Bendamustine-rituximab (BR) combined therapy for treatment of immuno-mediated neuropathies associated with hematologic malignancy. J Neurol Sci 413:116777
Broglio L, Lauria G (2005) Worsening after rituximab treatment in anti-mag neuropathy. Muscle Nerve 32:378–379
Noronha V, Fynan TM, Duffy T (2006) Flare in neuropathy following rituximab therapy for Waldenstrom’s macroglobulinemia. J Clin Oncol 24:e3
Gironi M, Saresella M, Ceresa L, Calvo M, Ferrante P, Merli F, Nemni R (2006) Clinical and immunological worsening in a patient affected with Waldenstrom macroglobulinemia and anti-mag neuropathy after treatment with rituximab. Haematologica 91(6 Suppl):ECR17
Benedetti L, Franciotta D, Vigo T, Grandis M, Fiorina E, Ghiglione E, Roccatagliata L, Mancardi GL, Uccelli A, Schenone A (2007) Relapses after treatment with rituximab in a patient with multiple sclerosis and anti myelin-associated glycoprotein polyneuropathy. Arch Neurol 64:1531–1533
Stork AC, Notermans NC, Vrancken AF et al (2013) Rapid worsening of IgM anti-MAG demyelinating polyneuropathy during rituximab treatment. J Peripher Nerv Syst 18:189–191
Sala E, Robert-Varvat F, Paul S, Camdessanché JP, Antoine JC (2014) Acute neurological worsening after rituximab treatment in patients with anti-MAG neuropathy. J Neurol Sci 345:224–227
Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M (2014) Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 370:1101–1110
Goede V, Fischer K, Engelke A, Schlag R, Lepretre S, Montero LFC, Montillo M, Fegan C, Asikanius E, Humphrey K, Fingerle-Rowson G, Hallek M (2015) Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia 29:1602–1604
Rakocevic G, Martinez-Outschoorn U, Dalakas MC (2018) Obinutuzumab, a potent anti-B-cell agent, for rituximab-unresponsive IgM anti-MAG neuropathy. Neurol Neuroimmunol Neuroinflamm 5:e460
Briani C, Visentin A, Salvalaggio A, Cacciavillani M, Trentin L (2019) Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy. Eur J Neurol 26:371–375
Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba ML, Advani RH (2015) Ibrutinib in previously treated Waldenström’s macroglobulinemia. N Engl J Med 372:1430–1440
Briani C, Visentin A, Cerri F, Quattrini A (2020) From pathogenesis to personalized treatments of neuropathies in hematological malignancies [published online ahead of print, J Peripher Nerv Syst 2020 Jul 20]
Vos JM, Notermans NC, D’Sa S et al (2018) High prevalence of the MYD88 L265P mutation in IgM anti-MAG paraprotein-associated peripheral neuropathy. J Neurol Neurosurg Psychiatry 89:1007–1009
Gavriatopoulou M, Fotiou D, Ntanasis-Stathopoulos I, Dimopoulos MA (2020). The current role of BTK inhibitors in the treatment of Waldenstrom's Macroglobulinemia. Expert Rev Anticancer Ther. 20(8):663–674
Dimopoulos MA, Trotman J, Tedeschi A, Matous JV, Macdonald D, Tam C, Tournilhac O, Ma S, Oriol A, Heffner LT, Shustik C, García-Sanz R, Cornell RF, de Larrea CF, Castillo JJ, Granell M, Kyrtsonis MC, Leblond V, Symeonidis A, Kastritis E, Singh P, Li J, Graef T, Bilotti E, Treon S, Buske C, iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia (2017) Ibrutinib for patients with rituximab-refractory Waldenström’s macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol 18:241–250
Castellani F, Visentin A, Campagnolo M, Salvalaggio A, Cacciavillani M, Candiotto C, Bertorelle R, Trentin L, Briani C (2020) The Bruton tyrosine kinase inhibitor ibrutinib improves anti-MAG antibody polyneuropathy. Neurol Neuroimmunol Neuroinflamm 7:e720
Delmont E, Hiew FL, Cassereau J, Aubé-Nathier AC, Grapperon AM, Attarian S, Rajabally YA (2017) Determinants of health-related quality of life in anti-MAG neuropathy: a cross-sectional multicentre European study. J Peripher Nerv Syst 22:27–33
Rajabally YA, Delmont E, Hiew FL, Aubé-Nathier AC, Grapperon AM, Cassereau J, Attarian S (2018) Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: a multicentre European study. Eur J Neurol 25:135–141
Pruppers MHJ, Merkies ISJ, Lunn MPT, Notermans NC, IMAGiNe Study Group (2017) 230th ENMC International Workshop:: improving future assessment and research in IgM anti-MAG peripheral neuropathy: a consensus collaborative effort, Naarden, The Netherlands, 24–26 February 2017. Neuromuscul Disord 27:1065–1072
European Federation of Neurological Societies, Peripheral Nerve Society, van Schaik IN, Bouche P, Illa I, Léger JM, Van den Bergh P, Cornblath DR, Evers EM, Hadden RD, Hughes RA, Koski CL, Nobile-Orazio E, Pollard J, Sommer C, van Doorn PA (2006) European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Eur J Neurol 13:802–808
Joint Task Force of the EFNS and the PNS (2010) European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 15:295–301
Pestronk A, Cornblath DR, Ilyas AA, Baba H, Quarles RH, Griffin JW, Alderson K, Adams RN (1988) A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside. Ann Neurol 24:73–78
Pestronk A, Chaudhry V, Feldman E et al (1990) Lower motor syndrome defined by patterns of weakness, nerve conduction abnormalities, and high titers of anti-glicolipid antibodies. Ann Neurol 27:316–326
Krarup C, Stewart JD, Sumner AJ, Pestronk A, Lipton SA (1990) A syndrome of asymmetric limb weakness with motor conduction block. Neurology 40:118–127
Feldman EL, Bromberg MB, Albers JW, Pestronk A (1991) Immunosuppressive treatment in multifocal motor neuropathy. Ann Neurol 30:397–401
Comi G, Amadio S, Galardi G, Fazio R, Nemni R (1994) Clinical and neurophysiological assessment of immunoglobulin therapy in five patients with multifocal motor neuropathy. J Neurol Neurosurg Psychiatry 57:35–37
Tan E, Lynn J, Amato AA et al (1994) Immunosuppressive treatment of motor neuron syndromes. Attempts to distinguish treatable disease. Arch Neurol 51:194–200
Donaghy M, Mills KR, Boniface SJ, Simmons J, Wright I, Gregson N, Jacobs J (1994) Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry 57:778–783
Vrethem M, Lindvall B, Kihlstrand S, Bäckman E, Brismar T, Fredman P, Henriksson KG (1996) High-dose intravenous immunoglobulin therapy improved muscle strength in a patient with multifocal motor neuropathy and antibodies against the gycolipid LK1. Eur J Neurol 3:156–159
Berg LH, Lokhorst H, Wokke JHJ (1997) Pulsed high-dose dexamethasone is not effective in patients with multifocal motor neuropathy. Neurology 48:1135
Forestier N, Chassande B, Moulonguet A et al (1997) Multifocal motor neuropathy with conduction block: 39 cases. Rev Neurol 153:579–586
Carpo M, Cappellari A, Mora G, Pedotti R, Barbieri S, Scarlato G, Nobile-Orazio E (1998) Deterioration of multifocal motor neuropathy after plasma exchange. Neurology 50:1480–1482
Umapathi T, Hughes RA, Nobile-Orazio E, Léger JM (2015) Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy. Cochrane Database Syst Rev 4:CD003217
Piepers S, Van den Berg-Vos R, Van der Pol WL et al (2007) Mycophenolate mofetil as adjunctive therapy for MMN patients: a randomized, controlled trial. Brain 130:2004–2010
Léger JM, Guimarães-Costa R, Iancu Ferfoglia R (2015) The pathogenesis of multifocal motor neuropathy and an update on current management options. Ther Adv Neurol Disord 8:109–122
Hahn AF, Beydoun SR, Lawson V, IVIG in MMN Study Team, Oh M, Empson VG, Leibl H, Ngo LY, Gelmont D, Koski CL (2013) A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy. J Peripher Nerv Syst 18:321–330
Terenghi F, Cappellari A, Bersano A, Carpo M, Barbieri S, Nobile-Orazio E (2004) How long is IVIg effective in multifocal motor neuropathy? Neurology 62:666–668
Harbo T, Andersen H, Hess A, Hansen K, Sindrup SH, Jakobsen J (2009) Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial. Eur J Neurol 16:631–638
Kumar A, Patwa HS, Nowak RJ (2017) Immunoglobulin therapy in the treatment of multifocal motor neuropathy. J Neurol Sci 375:190–197
Cocito D, Merola A, Romagnolo A, Peci E, Toscano A, Mazzeo A, Gentile L, Russo M, Fazio R, Filosto M, Siciliano G, Schirinzi E, Nobile-Orazio E, Lopiano L (2016) Subcutaneous immunoglobulins in chronic inflammatory polyradiculoneuropathy and multifocal motor neuropathy: a different long term response? J Neurol Neurosurg Psychiatry 87:791–793
Meucci N, Cappellari A, Barbieri S, Scarlato G, Nobile-Orazio E (1997) Long term effect of intravenous immunoglobulins and oral cyclophosphamide in multifocal motor neuropathy. J Neurol Neurosurg Psychiatry 63:765–769
Iwasawa E, Ohkubo T, Kanouchi T, Kanda T, Mizusawa H, Yokota T (2017) Long-term effects of intravenous cyclophosphamide in combination with mesna provided intravenously and via bladder perfusion in a patient with severe multifocal motor neuropathy. Intern Med 56:1893–1896
Chaudhry V, Cornblath DR (2010) An open-label trial of rituximab (Rituxan®) in multifocal motor neuropathy. J Peripher Nerv Syst 15:196–201
Toscano A, Rodolico C, Benvenga S, Girlanda P, Laurà M, Mazzeo A, Nobile-Orazio E, Trimarchi F, Vita G, Messina C (2002) Multifocal motor neuropathy and asymptomatic Hashimoto’s thyroiditis: first report of an association. Neuromuscul Disord 12:566–568
Nobile-Orazio E, Terenghi F, Cocito D, Gallia F, Casellato C (2009) Oral methotrexate as adjunctive therapy in patients with multifocal motor neuropathy on chronic IVIg therapy. J Peripher Nerv Syst 14:203–205
Radziwill AJ, Botez SA, Novy J, Kuntzer T (2009) Interferon beta-1a as adjunctive treatment for multifocal motor neuropathy: an open label trial. J Peripher Nerv Syst 14:201–202
Fitzpatrick AM, Mann CA, Barry S, Brennan K, Overell JR, Willison HJ (2011) An open label clinical trial of complement inhibition in multifocal motor neuropathy. J Peripher Nerv Syst 16:84–91
Debs R, Reach P, Cret C, Demeret S, Saheb S, Maisonobe T, Viala K (2017) A new treatment regimen with high-dose and fractioned immunoglobulin in a special subgroup of severe and dependent CIDP patients. Int J Neurosci 127:864–872
Scott LJ (2011) Fingolimod: a review of its use in the management of relapsing-remitting multiple sclerosis. CNS Drugs 25:673–698
Kiessling P, Lledo-Garcia R, Watanabe SL et al (2017) The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: a randomized phase 1 study. Sci Transl Med 9:eaan1208
Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O’Brien F, Wang JJ, Mantegazza R, REGAIN Study Group (2017) Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol 16:976–986
Kieseier BC, Mathey EK, Sommer C, Hartung HP (2018) Immune-mediated neuropathies. Nat Rev Dis Primers 4:31
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Chiara Briani reports speaker and consulting honoraria from Akcea, Alnylam, and Pfizer, and travel grants from Kedrion, Alnylam, and CSL Behring. Dario Cocito received honoraria for lecturing from Baxter, CSL Behring, and Kedrion; he received personal compensation for serving on the Advisory Board of CSL Behring, Kedrion, and travel grants to attend scientific meetings from Baxter, Kedrion, and CSL Behring. Marta Campagnolo has received travel grants to attend scientific meetings from Kedrion, Alnylam, and Akcea. Pietro Emiliano Doneddu has received travel grants to attend scientific meetings from CSL Behring and Kedrion. Eduardo Nobile-Orazio reports personal fees for Advisory or Scientific Board from Kedrion Biopharma, Italy; Baxter/Takeda, USA/Japan; CSL Behring, Italy; LFB Biomedicaments and Biotechnologies, France; Astellas, the Netherlands; UCB Biopharma srl, Belgium; Argenx BVBA, Belgium; and Sanofi US Services, Inc., USA, outside the submitted work and travel grants to attend Scientific Meeting from Baxter, Grifols, and Kedrion, Italy.
Ethical approval
None.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Briani, C., Cocito, D., Campagnolo, M. et al. Update on therapy of chronic immune-mediated neuropathies. Neurol Sci 43 (Suppl 2), 605–614 (2022). https://doi.org/10.1007/s10072-020-04998-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-020-04998-y