Medication Summary
If associated conditions are identified (HIV infection, lupus, paraproteinemia, lymphoma), treat them accordingly. The mainstay of treatment is immunosuppressive or immunomodulatory intervention. [2, 3]
Immunomodulatory/immunosuppressive agents
Class Summary
These agents include intravenous immunoglobulin (IVIg), plasma exchange (PE), prednisone, azathioprine, methotrexate, mycophenolate, cyclosporine, and cyclophosphamide. Their use is based on the proposed pathogenesis of CIDP as an immune-mediated condition.
The FDA approved IVIg product, Gamunex for chronic inflammatory demyelinating polyneuropathy (CIDP). Approval was based on a clinical trial [4] that showed Gamunex effective at improving certain motor functions for up to 48 weeks after initial treatment compared with placebo. The Inflammatory Neuropathy Cause and Treatment scale (INCAT) was used to measure patients’ ability to perform tasks (eg, walking, motor hand tasks). Twenty-eight of 59 patients (47%) treated with Gamunex had significantly improved INCAT scores compared with 13 of 58 patients (22.4%) treated with placebo (25% difference; 95% CI 7-43%; p=0.006). Patients with improved INCAT scores participated in a follow-up trial for an additional 24 weeks; 86% who continued receiving Gamunex maintained their improved INCAT scores compared with 61% who received placebo during the follow-up trial.
In September 2017, the FDA approved Privigen (immune globulin intravenous [human] 10% liquid) for the treatment of adults with CIDP to improve neuromuscular disability. The approval was based on data from two Phase 3 studies, PATH and PRIMA. In PATH (n=207), 73% of patients were responsive to Privigen over 13 weeks, as measured by the adjusted score on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale. In PRIMA (n=28), 61% of patients were responsive to Privigen over 25 weeks, as measured by their adjusted INCAT score. [39, 38]
In March 2018, the FDA approved subcutaneous immune globulin (SCIg) (Hizentra) for treatment of CIDP. It is the first SCIg approved in the US for CIDP. Approval was based on data from the Polyneuropathy and Treatment with Hizentra (PATH) study. The PATH study demonstrated patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly]; 32.8% on high-dose Hizentra [0.4 g/kg weekly]) compared with placebo (63.2%). [40]
Plasma Exchange
Two controlled and blinded studies have confirmed benefit of plasma exchange. Proposed mechanism is removal of antibodies and complement components that are responsible for immune-mediated damage of peripheral nerves. Plasma removed from blood through method similar to dialysis. Requires 2 large-bore needles, one to remove whole blood and other to return blood cells with albumin and saline. Patients whose veins are not large enough for repeated needle insertions have double-lumen catheter placed, either Quinton catheter (can be kept in for few weeks) or Permacath (can remain inserted indefinitely). Has been shown to have similar efficacy as IVIg in treatment of CIDP.
Immunoglobulin, intravenous (Gamunex, Privigen)
Multiple clinical trials establish efficacy. Solution for IV infusion that is composed mostly of heterogenous human IgG but also small amounts of IgA and IgM. Its proposed mechanism of action based on thought that IVIg contains random set of antibodies that would neutralize immune factors, causing damage to peripheral nerve in CIDP. Used in infectious diseases to provide immediate passive immunity in situations in which time constraints do not allow development of active immunity via vaccination. Also used to treat multiple immune-mediated conditions, such as idiopathic thrombocytopenic purpura, GBS, and myasthenia gravis.
Activates complement cascade and provides multitude of antibodies capable of neutralization of many microorganisms, toxins, viruses, and presumably autoantibodies. Latter mechanism possibly underlies effect in CIDP. Several studies showed significant benefit in CIDP; this makes it useful alternative to plasmapheresis. On average, improvement seen by day 10 and continues through day 42.
Patients usually require repeated treatments every few weeks or months to maintain remission or treat recurrences.
Immune globulin SC (Hizentra)
SC immune globulin supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. The mechanism of action has not been fully explained, but may include immunomodulatory effects. It is indicated as maintenance therapy for patients with CDIP to prevent relapse of neuromuscular disability and impairment.
Prednisone
Oral corticosteroid that suppresses inflammation and immune responses by altering protein synthesis in cells. Naturally occurring hormone that crosses cell membranes to bind to cytoplasmic receptors. Some mechanisms of action in CIDP are altering mediator function at site of inflammation and suppressing immune response.
Studies have shown that 6 months of pulsed dexamethasone or 8 months of daily prednisone can achieve long-term remission in over 25% of patients. [3]
Azathioprine (Imuran)
Purine analog that decreases metabolism of purines and also may inhibit DNA and RNA synthesis. Reduces disability and symptoms of CIDP by suppressing immune-mediated damage to nerves. A small trial did not show any beneficial effect but data are insufficient to draw conclusions.
Mycophenolate (CellCept)
Prodrug for immunosuppressive agent mycophenolic acid. Inhibits lymphocyte purine synthesis by inhibiting enzyme inosine monophosphate dehydrogenase. Reports of efficacy but no large controlled trials.
Cyclosporine (Sandimmune, Neoral)
Cyclic polypeptide consisting of 11 amino acids; effective in many autoimmune conditions. Inhibits first phase of T cell activation and does not affect humoral immunity. By suppressing T cells, may inhibit cell-mediated nerve damage at site of inflammatory/immune reaction. Small trial showed efficacy but data still insufficient to draw conclusions.
Cyclophosphamide (Cytoxan)
Cell-cycle phase-nonspecific antineoplastic agent and immunosuppressant that acts as alkylating agent.
Antiepileptic medications
Class Summary
In patients with CIDP, a variety of medications is used for treatment of neuropathic pain. Antiepileptic medications are quite effective. The 2 most frequently used medications, gabapentin and carbamazepine, are described.
Gabapentin (Neurontin)
Known to effect to GABA, but exact binding site unknown. Also has effects on calcium channels. Mostly used for treatment of epilepsy and neuropathic pain; 100-, 300-, and 400-mg cap and 600- and 800-mg film-coated tab are available.
Carbamazepine (Tegretol)
Blocks use-dependent sodium channels and inhibits sustained repetitive firing as well as reduces posttetanic potentiation of synaptic transmission in spinal cord. Potent enzyme inducer that can induce own metabolism. Used as anticonvulsant and for treatment of neuropathic pain.
Available in chewable 100-mg tab, in tab of 200 mg, XR tab of 100, 200, and 400 mg, and as susp of 100 mg/5 mL.
Tricyclic antidepressants
Class Summary
These medications are used frequently for the treatment of neuropathic pain. The most traditionally used medication, amitriptyline, is discussed.
Amitriptyline
Tertiary amine TCA known to decrease reuptake of serotonin and norepinephrine. Has been used more than other newer TCAs and has more proven benefits, although other TCAs, such as desipramine and nortriptyline, are also quite potent and have fewer adverse effects.
Tab available in 10, 25, 50, 75, 100, and 150 mg.
Pregabalin
Thought to have similar mode of action to gabapentin. Clinical trials have shown efficacy for diabetic neuropathy and shingles induced neuropathic pain.
Duloxetine (Cymbalta)
Duloxetine clinical trials have shown efficacy in diabetic neuropathy pain and for depression.
It is a selective serotonin and norepinephrine reuptake inhibitor.
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Electromyography of a patient with chronic inflammatory demyelinating polyradiculoneuropathy illustrating conduction block, temporal dispersion of compound muscle action potential, prolonged distal latencies, and slowed conduction.
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Prolonged F wave latencies (normal is < 31).
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Electron micrograph of the peripheral nerve of a patient with chronic inflammatory demyelinating polyradiculoneuropathy. Note "onion bulb" formation in the myelin sheath of the nerve fibers due to continuous demyelination and remyelination. Courtesy of A. Sima, MD, Department of Pathology, Wayne State University.
