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October 2015; 2 (5) ArticleOpen Access

Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins

Luis Querol, Ricard Rojas-García, Jordi Diaz-Manera, Joseba Barcena, Julio Pardo, Angel Ortega-Moreno, Maria Jose Sedano, Laia Seró-Ballesteros, Alejandra Carvajal, Nicolau Ortiz, Eduard Gallardo, Isabel Illa
First published September 3, 2015, DOI: https://doi.org/10.1212/NXI.0000000000000149
Luis Querol
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Ricard Rojas-García
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Jordi Diaz-Manera
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Joseba Barcena
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Julio Pardo
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Angel Ortega-Moreno
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Maria Jose Sedano
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Laia Seró-Ballesteros
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Alejandra Carvajal
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Nicolau Ortiz
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Eduard Gallardo
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Isabel Illa
From the Neuromuscular Diseases Unit (L.Q., R.R.-G., J.D.-M., E.G., I.I.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro para la Investigación Biomédica en Red en Enfermedades Raras (L.Q., R.R.-G., J.D.-M., E.G., I.I.), CIBERER, Madrid, Spain; Neurology Department (J.B.), Hospital Universitario de Cruces, Universidad del País Vasco, Spain; Department of Neurology (J.P.), Hospital Clínico de Santiago, Santiago de Compostela, Spain; Department of Neurology (A.O.-M., A.C.), Hospital Virgen de las Nieves, Granada, Spain; Department of Neurology (M.J.S.), University Hospital “Marqués de Valdecilla” (IFIMAV) and University of Cantabria, Santander, Spain; Department of Neurology (L.S.-B.), Hospital Univeristari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain; and Department of Neurology (UHN) (N.O.), Hospital Universitari Sant Joan, Universitat Rovira i Virgili, Reus, Spain.
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Full PDF
Citation
Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins
Luis Querol, Ricard Rojas-García, Jordi Diaz-Manera, Joseba Barcena, Julio Pardo, Angel Ortega-Moreno, Maria Jose Sedano, Laia Seró-Ballesteros, Alejandra Carvajal, Nicolau Ortiz, Eduard Gallardo, Isabel Illa
Neurol Neuroimmunol Neuroinflamm Oct 2015, 2 (5) e149; DOI: 10.1212/NXI.0000000000000149

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    Figure 1 Clinical status and autoantibody titers in rituximab-treated patients with anti-CNTN1/NF155 chronic inflammatory demyelinating polyneuropathy

    Patient 1 improved dramatically after rituximab treatment in both Rasch-built Overall Disability Scale (R-ODS) and Overall Neuropathy Limitations Scale (ONLS) scores, reaching full recovery at 12 months (A). Anti–contactin-1 (CNTN1) antibody titers decreased rapidly and were undetectable as early as 6 months after treatment, whereas anti–tetanic toxoid (TT) antibodies remained stable after treatment (B). Patient 2 had marked improvement after rituximab treatment in both R-ODS and ONLS scores, although mild leg distal weakness persisted (C). Anti–neurofascin-155 (NF155) antibody titers decreased rapidly and remained low 18 months after treatment. Anti-TT antibodies, however, decreased immediately after treatment and stabilized thereafter (D). Patient 3 improved slightly after rituximab treatment in both R-ODS and ONLS scores, although marked disability persisted (E). This patient had a significantly longer disease duration (more than 15 years) and secondary axonal damage. Nevertheless, anti-NF155 antibody titers decreased rapidly after treatment and stabilized at a titer of 1/900. An additional rituximab course further decreased anti-NF155 antibody titers. Anti-TT antibodies remained stable after treatment (F). Arrows represent additional rituximab courses.

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    Figure 2 Clinical and autoantibody status of 2 CNTN1 or NF155+ patients not receiving rituximab

    Despite corticosteroids and methotrexate treatment, patient 5 remained significantly disabled but declined to be treated with rituximab and his clinical status and autoantibody levels remained stable (A). Patient 7 is the only patient from our cohort fully responding to corticosteroids. Clinical scales improved clearly and anti–contactin-1 (CNTN1) antibodies disappeared (B). NF155 = neurofascin-155; R-ODS = Rasch-built Overall Disability Scale.

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