Combination Versus Monotherapy in Acute Anti-LGI1 Encephalitis: A Real-World Dose Optimization Analysis

Area of Science:

• Neuroimmunology
• Clinical Neurology
• Pharmacology

Background:

• Anti-leucine-rich-glioma-inactivated 1 encephalitis (LGI1e) primarily affects older adults with comorbidities, necessitating optimized immunotherapy.
• This population is at higher risk for adverse effects from standard treatments.

Purpose of the Study:

• To compare the efficacy and safety of intravenous immunoglobulin (IVIg), intravenous methylprednisolone (IVMP) at 500 or 1000 mg/day, and combined IVIg with IVMP for LGI1e.
• To define an optimal immunotherapy regimen balancing efficacy and safety for LGI1e patients.

Main Methods:

• A cohort of 131 LGI1e patients was analyzed.
• Efficacy was assessed via response rate, latency, and improvements in CASE, mRS, MMSE, and FBDS.
• Safety was evaluated by incidence and severity of adverse events (AEs).

Main Results:

• Combination IVIg+IVMP showed superior response rates, shorter latency, and greater improvements in CASE, mRS, and FBDS compared to monotherapy.
• 1000 mg IVMP reduced latency and FBDS cessation time versus 500 mg, but response rates were similar.
• IVMP-containing regimens increased AEs, particularly at 1000 mg; diabetes was the sole independent AE risk factor. Cognitive impairment persisted as a major disability.

Conclusions:

• Combined IVIg and corticosteroid therapy is more effective than monotherapy for LGI1e.
• A starting IVMP dose of 500 mg is considered optimal for balancing efficacy and safety.
• Post-immunotherapy cognitive impairment requires sustained management, necessitating further validation in randomized trials.