Targeting CIDP Treatments and the Benefits of TPE

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Targeting CIDP Treatments and the Benefits of TPE

• Dobri D. Kiprov, M.D., H.P.
• Chief, Division of Immunotherapy,
• California Pacific Medical Center, San Francisco,
  California
• Medical Director, Apheresis Care Group,
• Fresenius Medical Care Extracorporeal Alliance

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CIDP Chronic Inflammatory Demyelinating
Polyneuropathy

• Prevalence 1.9 7.7 per 100,000
• Unknown etiology
• Autoimmune pathogenesis
• Broad clinical spectrum

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CIDP Clinical Characteristics

• Acquired immune mediated peripheral neuropathy
• Steadily progressive
• Chronic monophasic
• Recurrent
• Symmetric involvement
• Both proximal and distal muscles
• Both sensory and motor
• Cranial nerves and respiratory muscles
• Research diagnostic criteria of the American
  Academy of Neurology

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CIDP Disease Association

• Idiopathic
• Associated with
• HIV
• Diabetes mellitus
• Monoclonal gammopathies
• Castlemans disease
• POEMS syndrome
• SLE
• Transplantation
• Hepatitis
• Vaccination

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CIDP - Pathology
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Experimental Autoimmune Neuritis (EAN)
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Animal Models of EAN
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Autoimmunity

• The immune system attacks foreign antigens
• In autoimmune conditions the immune system
  attacks self tissues
• Molecular mimicry

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CIDP - Immunopathogenesis

• Molecular mimicry
• Proceeding infection
• Vaccination
• Associated with melanoma
• melanoma and Schwann cells derive from neural
  crest tissues and share common antigens
• melanoma antigens carbohydrate epitopes
  gangliosides GM2, GM3, GD2, GD3
• monoclonal abs against melanoma cell lines
  react with MAG and other myelin glycoproteins

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Infectious agent
APC
IL-4 , IL-6
Antibodies
B-cell
T-cell
Plasma cell
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Neuroimmnology
Kieseier BC et al. Muscle Nerve 2004 Aug 30131-56
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Neuroimmunology 1
NONitric oxide MMPmatrix metalloproteinase
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Anti-myelin Antibodies
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Treatment of CIDP

• Corticosteroids
• Plasmapheresis
• IVIG (currently first line of treatment)
• Immunosupressive drugs
• Azathiopprine
• Cyclosporine
• IFN-beta (safe but not effective)

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Plasmapheresis vs. IVIG in CIDP

• IVIG 63 improvement
• Plasmapheresis 80 improvement
• In some studies patients who do not respond to
  steroids and plasmapheresis respond to IVIG

Hahn,AF et al., Brain 1996 Vol. 119, pp.
1055-1067
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CIDP in Diabetes Mellitus
The incidence of DM-CIDP was 11 times higher
than in non-diabetic patients
Department Neurology, University of Miami,
Sharma, K, et al. Arch Neurol V.59, May 2002
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CIDP in Diabetes MellitusResponse to IVIG
Patients who had conduction block did better
(100) vs. 66.7
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Polyneuropathies associated with HIV

• GBS like syndrome
• CIDP like syndrome
• Degenerative neuropathy
• CMV neuropathy
• Drug related neuropathy

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CIDP in HIV Infection

• Autoimmune Polyneuropathy
• Treatment
• Plasmapheresis
• IVIG
• Plasmapheresis and IVIG
• Kiprov, et al. J. Clin Apheresis, 1988, V. 4, p.
  3-7

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Lower Motor Neuron Syndrome

• Multifocal motor neuropathy
• Multifocal conductive block
• Lower motor neuron syndrome
• predominantly distal involvement
• Treatment
• IVIG
• Cyclophosphamide
• Rifuximals
• Plasmapheresis usually ineffective

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CIDP associated with Cryoglobulinemia

• Treatment
• Plasmapheresis
• IFN alpha or ribavarin
• Rifuximals

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CIDP and Monoclonal Gammopathies

• Waldenstroms
• B-cell lymphoma
• Multiple myeloma
• CLL
• MGUS

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Plasmapheresis and IVIG

• Friend or Foe?

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Mechanism of Action

• Plasmapheresis
• Removal of antibodies and other substances from
  the circulation
• removal of antibodies from tissue
• cellular immunomodulation
• IVIG
• Blocks autoantibodies
• Blocks complement activation
• Inhibits pro-inflammatory cytokines
• Antibodies bind to B and T cell receptors and
  affect cellular immunity

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Polymyositis Associated with Monoclonal Gammopathy
At diagnosis
After a month of plasmapheresis
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Effect of Plasmapheresis on Cellular Immunity
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Cost Analysis
Ferguson, et al. Transfusion 2005, V.45, p
1640-1657
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Immunologically Mediated Polyneuropathies