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

Neurol Neuroimmunol Neuroinflamm. 2020 Apr 13;7(4):e720. doi: 10.1212/NXI.0000000000000720. Print 2020 Jul.


Objective: 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).

Methods: All 3 patients underwent bone marrow biopsy showing WM, with MYD88 L265P mutated and CXCR4S338X 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.

Results: 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.

Conclusion: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases of the Nervous System / drug therapy*
  • Autoimmune Diseases of the Nervous System / immunology
  • Female
  • Humans
  • Male
  • Myelin-Associated Glycoprotein / immunology*
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Polyneuropathies / drug therapy*
  • Polyneuropathies / immunology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Treatment Outcome
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / immunology


  • MAG protein, human
  • Myelin-Associated Glycoprotein
  • Piperidines
  • Protein Kinase Inhibitors
  • ibrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • Adenine