Table 2

Immunotherapeutic options for treatment of autoimmune encephalitis

ImmunotherapyMechanism of actionDose/regimenMonitoring/prophylactic adjunctive therapiesSide-effects
First-line therapy
CorticosteroidsMultiple: 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.
PlasmapheresisBulk 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
MycophenolateActive 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.
AzathioprineInhibition 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.
RituximabMonoclonal 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).
CyclophosphamideInduction 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.
TocilizumabMonoclonal 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.
BortezimibSmall-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.