Table 3.
Summary of immunomodulatory agents.
Adapted from Husari and Dubey Autoimmune Epilepsy. Neurotherapeutics. 2019 [174]
| Immunomodulatory agent | Route of administration | Dosing/regimen | Mechanism of action | Adverse effects | Monitoring and prophylaxis |
|---|---|---|---|---|---|
| Corticosteroids | IV or PO |
Initial dose: IV methylprednisolone (1 g per day for 3–5 days) 6-week trial: 1 g per day for 3 days followed by once weekly for 5 weeks 12 week trial: 1 g per day for 3 days followed by once weekly for 5 weeks, followed by once every 2 weeks for 6 weeks Oral maintenance: 60–80 mg prednisone daily, duration of taper variable |
-Acts on nuclear glucocorticoids receptors to reduce cytokine and chemokine production -Reduces migration of leukocytes to the target tissue |
Insomnia, psychiatric dysfunction, hyperglycemia, electrolyte imbalances, fluid retention, hypertension, peptic ulcer, Cushing syndrome, cataracts, infections, osteoporosis and avascular necrosis Addisonian crisis on rapid withdrawal of corticosteroids |
-Blood pressure, serum electrolytes and glucose monitoring - PJP ppx: TMP/SMX - osteoporosis ppx: Vitamin D + calcium - GI ppx: PPI or H2 blocker |
| Plasmapheresis | IV | 1 exchange every other day for 10–14 days | -Extracorporeal blood filtration designed to remove large molecular weight molecules, including immunoglobulins, immune complex, and complements | Hypotension, electrolyte imbalance, perioral paresthesia (hypocalcemia), coagulopathy, central line infection, hemorrhage, thrombosis and pneumothorax | PT, INR, PTT, Fibrinogen |
| IVIG | IV |
Initial dose 2 g/kg daily divided over 4–5 days maintenance: 1–2 g/kg every 3–4 weeks |
Remains unclear Interaction with antigen-binding fragment on the antibodies and/or crystalizable fragment on the antibodies or the antigen presenting cells |
Headache, aseptic meningitis, acute renal failure, thrombotic/thromboembolic events anaphylaxis due to IgA deficiency | Electrolytes, renal function |
| Rituximab | IV | 1000 mg followed by 2nd dose in 2 weeks, or 375 mg/m2 weekly for 4 weeks | B-cell depletion by antibody dependent cellular cytotoxicity, complement dependent cytotoxicity and apoptosis | Allergic reaction, opportunistic infection, reactivation of tuberculosis infection or hepatitis B infection, PML | Hepatitis B antibodies, Quatiferon test (for latent tuberculosis), pregnancy test, Liver function test |
| Cyclophosphamide | IV or PO |
IV: 500-1000 mg/m2/month PO: 1–2 mg/kg/day (renal adjustment necessary) |
Alkylating agent with interferes with DNA synthesis | Gastrointestinal (nausea, vomiting), hair loss, mucositis, hemorrhagic cystitis, infertility and myelosuppression |
CBC, liver function test, creatinine CBC at 8–14 days post infusion, increased hydration recommended |
| Mycophenolate | PO | Initially 500 mg twice daily, target 1000 mg twice daily | Inhibition of inosine monophosphate dehydrogenase mediated guanosine nucleotide synthesis | Gastrointestinal (nausea, vomiting, diarrhea), hypertension, peripheral edema, infections, myelosuppression, lymphoma |
CBC, creatinine, urine pregnancy test CBC once per week for 1 month, then once every 2 weeks for 2 months then once every 1–3 months for the duration of therapy |
| Azathioprine | PO | Initially 1.5 mg/kg/day, target 2–3 mg/kg/day (guided by 5-point MCV increase from baseline) | Converted to cytotoxic 6-thioguanine nucleotides which leads to incorporation as a false base into DNA inducing lymphocyte apoptosis | Gastrointestinal symptoms (nausea, vomiting, diarrhea), hypersensitivity reactions, hair loss, cytopenia, hepatotoxicity, lymphoma and infections |
CBC, liver function test, creatinine, TPMT and urine pregnancy CBC should be checked once per week for 1 month, then once every 2 weeks for 2 months, then once every 1–3 months for the duration of therapy |
IV = intravenous, PO = per oral; PLEX = plasmapheresis; IVIG = intravenous immunoglobulin; PT = prothrombin time; INR = international normalized ratio; PTT = partial thromboplastin time; CBC = complete blood count; TPMT = thiopurine S-methyltransferase; TMP = trimethoprim; SMX = sulfamethoxazole; PPI = proton pump inhibitor; H2 = histamine 2; PML = progressive multifocal leukoencephalopathy; ppx = prophylaxis