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      The Bruton tyrosine kinase inhibitor ibrutinib improves anti-MAG antibody polyneuropathy


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          To assess whether neuropathy with anti-myelin-associated glycoprotein (MAG) antibody may improve after treatment with ibrutinib, an oral inhibitor of Bruton tyrosine kinase, we prospectively treated with ibrutinib a cohort of 3 patients with anti-MAG neuropathy and Waldenström macroglobulinemia (WM).


          All 3 patients underwent bone marrow biopsy showing WM, with MYD88 L265P mutated and CXCR4 S338X wild type, and were started on ibrutinib 420 mg/die. Patients were assessed at baseline, at 3-6-9 months, and at 12 months in 2 patients with a longer follow-up, using Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score, INCAT sensory sum score, and Medical Research Council sum score. The modified International Cooperative Ataxia Rating Scale was performed in 2 patients, whereas it was not used in the patient with Parkinson disease as a major comorbidity. Responders were considered the patients improving by at least one point in 2 clinical scales.


          All the patients reported an early and subjective benefit, consistent with the objective improvement, especially of the sensory symptoms as shown by clinical scales. Treatment was well tolerated.


          These preliminary data point to a possible efficacy of ibrutinib in anti-MAG antibody neuropathy, which is the most common disabling paraproteinemic neuropathy, where active treatment is eagerly needed.

          Classification of evidence

          This study provides Class IV evidence that for patients with anti-MAG antibody neuropathy, ibrutinib improves neuropathy symptoms.

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          Most cited references9

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          Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial.

          In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease.
            • Record: found
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            Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.

            This multicenter, randomized, double-blind, crossover trial compared a six week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the thirty-two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11-point disability scale two weeks after randomization. There was slightly, but not significantly, more improvement after IVIg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = -0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring IVIg in the secondary outcome measures: time to walk 10 meters after two weeks and improvement in disability grade after six weeks. Results may have been biased against IVIg by the eight patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in one patient while on prednisolone and in none with IVIg.
              • Record: found
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              Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS.

              To develop a brief ataxia rating scale (BARS) for use by movement disorder specialists and general neurologists. Current ataxia rating scales are cumbersome and not designed for clinical practice. We first modified the International Cooperative Ataxia Rating Scale (ICARS) by adding seven ataxia tests (modified ICARS, or MICARS), and observed only minimally increased scores. We then used the statistics package R to find a five-test subset in MICARS that would correlate best with the total MICARS score. This was accomplished first without constraints and then with the clinical constraint requiring one test each of Gait, Kinetic Function-Arm, Kinetic Function-Leg, Speech, and Eye Movements. We validated these clinical constraints by factor analysis. We then validated the results in a second cohort of patients; evaluated inter-rater reliability in a third cohort; and used the same data set to compare BARS with the Scale for the Assessment and Rating of Ataxia (SARA). Correlation of ICARS with the seven additional tests that when added to ICARS form MICARS was 0.88. There were 31,481 five-test subtests (48% of possible combinations) that had a correlation with total MICARS score of > or =0.90. The strongest correlation of an unconstrained five-test subset was 0.963. The clinically constrained subtest validated by factor analysis, BARS, had a correlation with MICARS-minus-BARS of 0.952. Cronbach alpha for BARS and SARA was 0.90 and 0.92 respectively; and inter-rater reliability (intraclass correlation coefficient) was 0.91 and 0.93 respectively. BARS is valid, reliable, and sufficiently fast and accurate for clinical purposes.

                Author and article information

                Neurol Neuroimmunol Neuroinflamm
                Neurol Neuroimmunol Neuroinflamm
                Neurology® Neuroimmunology & Neuroinflammation
                Lippincott Williams & Wilkins (Hagerstown, MD )
                July 2020
                13 April 2020
                13 April 2020
                : 7
                : 4
                : e720
                From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
                Author notes
                Correspondence Dr. Briani chiara.briani@ 123456unipd.it

                Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.


                The authors share the first authorship.

                The Article Processing Charge was funded by the authors.

                Author information
                Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                : 23 December 2019
                : 12 March 2020
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