Clinical outcomes and prognostic factors after first- and second-line immunotherapy in a cohort of 57 patients with refractory autoimmune encephalitis.

Background: Refractory autoimmune encephalitis (AE) is a severe condition with limited real-world evidence on treatment outcomes and prognostic factors. This study evaluated clinical outcomes and factors associated with 6-month functional recovery in a strictly defined refractory AE cohort. Methods: This single-center retrospective cohort study screened 246 potentially eligible AE records from 2018 to 2025 and included 57 patients who fulfilled the prespecified refractory AE criteria and had ascertainable 6-month functional outcomes. Second-line immunotherapy was subsequently administered to a subset of patients. The primary outcome was 6-month functional status assessed by the modified Rankin Scale (mRS) after refractory-state adjudication, with favorable outcome defined as mRS 0-2. Multivariable logistic regression, adjusted for baseline severity and constrained by the limited number of unfavorable outcomes, examined factors associated with 6-month functional outcome. Results: All 57 patients fulfilled the harmonized refractory criterion after inadequate response to first-line immunotherapy. Second-line escalation was subsequently administered to 14 patients (24.6%), whereas 43 (75.4%) did not receive second-line therapy. Favorable 6-month outcomes occurred in 9/14 (64.3%) and 28/43 (65.1%), respectively. Conclusions: In the parsimonious multivariable analysis, higher mRS at refractory-state adjudication and ICU admission were associated with unfavorable 6-month functional outcome. The association with ICU admission persisted after adjustment for mRS, but its magnitude was imprecisely estimated and likely overlaps with the underlying construct of disease severity. These findings should therefore be considered exploratory prognostic associations rather than definitive independent predictors.