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Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy

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Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5–35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60–150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.

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References

  1. Cornblath DR, Feasby TE, Hahn AF et al (1991) Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Ad hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Neurology 41:617–618

    Google Scholar 

  2. Lunn MP, Manji H, Choudhary PP et al (1999) Chronic inflammatory demyelinating polyneuropathy: a prevalence study in southeast England. J Neurol Neurosurg Psychiatry 66:677–680

    Article  CAS  PubMed  Google Scholar 

  3. Gold R, Archelos JJ, Hartung HP (1999) Mechanisms of immune regulation in the peripheral nervous system. Brain Pathol 9:343–360

    Article  CAS  PubMed  Google Scholar 

  4. Hughes RAC, Allen D, Mekowska A et al (2006) Pathogenesis of chronic inflammatory demyelinating polyradiculopathy. J Peripher Nerv Syst 11:30–46

    Article  PubMed  Google Scholar 

  5. Feasby TE, Hahn AF, Koopman WJ et al (1990) Central lesions in chronic inflammatory demyelinating polyneuropathy: an MRI study. Neurology 40:476–478

    CAS  PubMed  Google Scholar 

  6. Hartung HP, Willison H, Jung S et al (1996) Autoimmune responses in peripheral nerve. Springer Semin Immunopathol 18:97–123

    Article  CAS  PubMed  Google Scholar 

  7. Harvey GK, Gold R, Toyka KV, Hartung HP (1995) Nonneural-specific T lymphocytes can orchestrate inflammatory peripheral neuropathy. Brain 118:1263–1272

    Article  PubMed  Google Scholar 

  8. Hadden RDM, Hughes RAC (2003) Management of inflammatory neuropathies. J Neurol Neurosurg Psychiatry 74(Suppl II):9–14

    Google Scholar 

  9. Duhem C, Dicato MA, Ries F (1994) Side-effects of intravenous immunoglobulins. Clin Exp Immunol 97(Suppl 1):79–83

    PubMed  Google Scholar 

  10. Van Schik IN, Winer JB, de Haan R et al. Intravenous immunoglobulin for chronic inflammatory demyelinating polyneuropathy. Cochrane Database of Systematic Reviews 2002; Issue 2. Art no CD001797. doi:10.1002/14651858.CD001797

  11. Hughes RAC, Swan AV, Van Doorn PA. Cytotoxic drugs and interferons for chronic inflammatory demyelinating polyneuropathy. Cochrane Database of Systematic Reviews 2004; Issue 4. Art. No. CD003280. doi:10.1002/14651858. CD003280.pub2

  12. Gorson KC, Natarajan N, Ropper AH et al (2007) Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial. Muscle Nerve 35:66–69

    Article  CAS  PubMed  Google Scholar 

  13. Hale G, Xia MQ, Tighe Hp et al (1990) The CAMPATH 1-H antigen (CDw52). Tissue Antigens 35:118–127

    Article  CAS  PubMed  Google Scholar 

  14. Brett S, Baxter G, Cooper H et al (1996) Repopulation of blood lymphocytes sub-populations in rheumatoid arthritis patients treated with the depleting humanixed monoclonal antibody, CAMPATH-1H. Immunology 88:13–19

    Article  CAS  PubMed  Google Scholar 

  15. Moreau T, Coles AJ, Wing M et al (1996) Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 119:225–237

    Article  PubMed  Google Scholar 

  16. Coles A, Deans J, Compston A (2004) Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench. Clin Neurol Neurosurg 106:270–274

    Article  PubMed  Google Scholar 

  17. Waldmann H, Polliak A et al (1984) Elimination of graft-versus-host disease by in vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH-1). Lancet 2(8401):483–486

    Article  CAS  PubMed  Google Scholar 

  18. Hale G, Waldmann H (1996) Recent results using CAMPATH-1 antibodies to control GVHD and graft rejection. Bone Marrow Transplant 17(3):305–308

    CAS  PubMed  Google Scholar 

  19. Matteson EL, Yocum DE et al (1995) Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection. Arthritis Rheum 38(9):1187–1193

    Article  CAS  PubMed  Google Scholar 

  20. Weinblatt ME, Maddison PJ et al (1995) CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study. Arthritis Rheum 38(11):1589–1594

    Article  CAS  PubMed  Google Scholar 

  21. Isaacs JD, Hale G et al (1995) Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H. Br J Ophthalmol 79(11):1054–1055

    Article  CAS  PubMed  Google Scholar 

  22. Dick AD, Meyer P et al (2000) Campath-1H therapy in refractory ocular inflammatory disease. Br J Ophthalmol 84(1):107–109

    Article  CAS  PubMed  Google Scholar 

  23. Osterborg A, Fassas AS et al (1996) Humanized CD52 monoclonal antibody Campath-1H as first-line treatment in chronic lymphocytic leukaemia. Br J Haematol 93(1):151–153

    Article  CAS  PubMed  Google Scholar 

  24. Lockwood CM, Hale G et al (2003) Remission induction in Behcet’s disease following lymphocyte depletion by the anti-CD52 antibody CAMPATH 1-H. Rheumatology (Oxford) 42(12):1539–1544

    Article  CAS  Google Scholar 

  25. Lundin J, Hagberg H et al (2003) Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 101(11):4267–4272

    Article  CAS  PubMed  Google Scholar 

  26. Killick SB, Marsh JC et al (1997) Sustained remission of severe resistant autoimmune neutropenia with Campath-1H. Br J Haematol 2:306–308

    Article  Google Scholar 

  27. Isaacs JD, Hazleman BL et al (1996) Monoclonal antibody therapy of diffuse cutaneous scleroderma with CAMPATH-1H. J Rheumatol 23(6):1103–1106

    CAS  PubMed  Google Scholar 

  28. CAMMS trial Investigators (2008) Alemtuzumab vs Interferon Beta-1a in early multiple sclerosis. N Engl J Med 359(17):1786–1801

    Article  Google Scholar 

  29. Zephir H, Stojkovic T, Latour P et al (2006) Relapsing demyelinating disease affecting both the central and peripheral nervous systems. J Neurol Neurosurg Psychiatry 79:1032–1039

    Article  Google Scholar 

  30. Iles Z, Shimamura M, Newcombe J et al (2004) Accumulation of Valpha7.2-Jalpha33 invariant T cells in human autoimmune inflammatory lesions in the nervous system. Int Immunol 16:223–230

    Article  Google Scholar 

  31. Hirst CL, Raasch S, Llewelyn GL et al (2006) Remission of chronic inflammatory demyelinating polyneuropathy after alemtuzumab (Campath 1H). J Neurol Neurosurg Psychiatry 77:800–802

    Article  CAS  PubMed  Google Scholar 

  32. Jones JL, Phuah CL, Cox AL et al (2009) IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Invest 119(7):2052–2061

    CAS  PubMed  Google Scholar 

  33. Coles AJ, Wing M, Smith S et al (1999) Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 354:1691–1695

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK

    E. A. Marsh, C. L. Hirst, J. G. Llewelyn, M. D. Cossburn & N. P. Robertson

  2. MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK

    M. M. Reilly

  3. The Walton Centre for Neurology and Neurosurgery, Liverpool, Lower Lane, Fazakerley, Liverpool, L9 7LJ, UK

    A. Krishnan & M. Doran

  4. Department of Neurology, Cork University Hospital, Wilton, Cork, County Cork, Ireland

    A. M. Ryan

  5. Department of Clinical Neurosciences, University of Cambridge, Box 165, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    A. J. Coles & J. L. Jones

Authors
  1. E. A. Marsh
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  2. C. L. Hirst
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  3. J. G. Llewelyn
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  4. M. D. Cossburn
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  5. M. M. Reilly
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  6. A. Krishnan
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  7. M. Doran
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  8. A. M. Ryan
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  9. A. J. Coles
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  10. J. L. Jones
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  11. N. P. Robertson
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Correspondence to N. P. Robertson.

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Marsh, E.A., Hirst, C.L., Llewelyn, J.G. et al. Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy. J Neurol 257, 913–919 (2010). https://doi.org/10.1007/s00415-009-5437-3

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  • DOI: https://doi.org/10.1007/s00415-009-5437-3

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