Immunotherapeutic options for treatment of autoimmune encephalitis
| Immunotherapy | Mechanism of action | Dose/regimen | Monitoring/prophylactic adjunctive therapies | Side-effects |
| First-line therapy | ||||
| Corticosteroids | Multiple: largely via attenuation of immune response via genomic and non-genomic effects. | Methylprednisolone 1 g intravenous daily×3–5 days. +/- Oral prednisone 1 mg/kg/day. Slow steroid taper. | Clinical monitoring for steroids side effects. Calcium, vitamin D±bisphosphonate therapy. Proton pump inhibitor for long steroid tapers. When in combination with other immunotherapy, consider prophylaxis for Pneumocystis jirovecii. | Sleep disruption, irritability, osteoporosis, weight gain, hypertension, hyperglycaemia, increased intraocular pressures, upper gastrointestinal bleeding, skin thinning/bruising/ striae, reactivation of chronic infection, suppression of endogenous steroid production,. Rare complications include: avascular necrosis of jaw or hip, P. jirovecii pneumonia. |
| Intravenous immunoglobulin (IVIG) | Very wide to include modulation of T/B-cells, cytokines and innate pathways. Blockade of variable domain of causative antibodies by anti-idiotype antibodies. | 2 g/kg intravenous divided over 3–5 days. | Clinical monitoring for allergic reactions, transfusion reactions, aseptic meningitis. | Transfusion reactions (most mild), rare complications include aseptic meningitis, anaphylaxis, acute renal failure, haemolytic anaemia and thromboembolism. |
| Plasmapheresis | Bulk removal of circulating immunoglobulins. Rebound state may increase susceptibility of circulating antibody-secreting cells and precursors to cytotoxic therapies (ie, cyclophosphamide). | 3–5 sessions over 5–10 days. | Clinical monitoring for hypotension, catheter-related complications (thrombosis, infection, air embolism) and anaphylaxis. Monitoring for electrolyte abnormalities throughout. | Mortality 3–5 per 10 000, hypocalcaemia, hypokalaemia, metabolic alkalosis, hypotension, catheter-related complications (thrombosis, infection, air embolism), anaphylaxis, TRALI and rare viral transmission |
| Second-line therapy | ||||
| Mycophenolate | Active metabolite (mycophenolic acid) inhibits inosine-5′-monophosphate dehydrogenase, depletes guanosine nucleotides preferentially in T and B lymphocytes. | Initially 500 mg two times a day, targeting to 1–1.5 g two times a day maintenance. | Before starting: screening for latent HBV, HCV. CBC-D weekly×1 month, q2weeks×2 months→monthly. Electrolytes, Cr/GFR, ALT, AST, ALP, GGT, bilirubin, albumin, INR monthly. | Increased infection risk including reactivation of viral infections (herpes simplex/zoster, polyomavirus (BK virus) associated nephropathy (PVAN), PML and CMV viraemia), increased risk of lymphoma and skin malignancy, cytopenias. |
| Azathioprine | Inhibition of purine synthesis via active metabolites 6-mercaptopurine and 6-thioguanine. | Initial 50 mg daily, increase by 50 mg increments q1-2 weeks until 2 to 3 mg/kg/day maintenance. | CBC-D weekly×1 month, q2 weeks×2 months→monthly. ALT, AST, GGT, ALP, bilirubin, albumin, INR q3months. Age-related cancer screening and skin checks. Consider testing for thiopurine S-methyltransferase (TMPT) deficiency before initiation. | GI toxicity, dose-related cytopenias, hepatotoxicity, increased infection rates, increased risk of malignancy (including the rare entity hepatosplenic T-cell lymphoma (HSTCL), PML. |
| Rituximab | Monoclonal antibody against CD20: principally B cell depletion. | Induction: 375 mg/m2 intravenous weekly×4 weeks or 500 mg intravenous×2 doses separated by 2 weeks. | Preinitiation: CBC+differential, ALT, AST, LDH, bilirubin, electrolytes, creatinine, screening for latent HBV, HCV, syphilis, HIV, and TB. Monthly postinfusion bloodwork (starting 1-week post-induction): CBC-D, ALT, AST, LDH, bilirubin, electrolytes, Cr. | Mild transfusion-related reactions (headache, fever, chills, nausea), hypotension, anaphylaxis (rare), reactivation of latent infection (TB, hepatitis B). |
| Cyclophosphamide | Induction of DNA cross-linking and apoptosis by active metabolite (phosphoramide mustard). | 750 mg/m2 intravenous monthly for 3–6 months. | CBC, HIV, HBV, HCV, VZV, liver enzymes, electrolytes, creatinine+urinalysis weekly for the first 4 weeks, then q 2 weekly for next 2 months→monthly. | Cytopenias (neutropenia most common), nausea/vomiting, diarrhoea, hair loss, mucocutaneous ulceration, haemorrhagic cystitis, infertility, teratogenicity. |
| Third-line/experimental | ||||
| Tocilizumab | Monoclonal antibody against IL-6, blocking binding to IL-6 receptor and preventing IL-6 mediated inflammatory cascade. | Initial: 4 mg/kg intravenous infusion. May increase to 8 mg/kg based on response. | Preinitiation screening for TB. Clinical monitoring for infection. Regular monitoring of blood counts, liver profile and lipids. | Fever response and CRP elevation may be blunted by impairment in IL-6 receptor signalling. Hepatotoxicity, cytopenias, blood lipid abnormalities, immunosuppression. |
| Bortezimib | Small-molecule proteasome inhibitor. Relatively selective depletion of plasma cells due to high immunoglobulin synthesis rate. | Peripheral neuropathy, myalgia, diarrhoea | ||
Sources: Sun et al, Shin et al,2 62 63 Joint Formulary Committee.
ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CBC-D, complete blood count with differential; CD, cluster of differentiation; Cr, creatinine; CRP, C reactive protein; GFR, glomerular filtration rate; GGT, gamma-glutamyltransferase; HBV/HCV, hepatitis B/C virus; HIV, human immunodeficiency virus; HTLV, human T-lymphotrophic virus; IL, interleukin; TB, tuberculosis; TRALI, transfusion associated lung injury.