Abstract
Objectives This systematic review and meta-analysis examined whether second-line immunotherapy is associated with improved functional outcomes in patients with autoimmune encephalitis.
Methods We included observational cohort studies reporting at least five adult patients with autoimmune encephalitis, treated with either second-line immunotherapy or first-line immunotherapy alone, and reporting outcomes using the modified Rankin scale (mRS; search date 22 April 2020). We performed one-stage individual patient data (IPD) meta-analyses using generalised linear multi-level mixed-effects regression models.
Results IPD was obtained for 356 patients from 25 studies. Most studies were rated as moderate to high risk of bias. Seventy-one patients (71/356, 19%) were treated with second-line immunotherapy. We did not find a statistically significant association between treatment with second-line immunotherapy and final mRS score for the cohort overall (odds ratio (OR) 1.74, 95% CI 0.98–3.08, p = 0.057), or sub-groups with NMDA-receptor encephalitis (OR 1.03, 95% CI 0.45–2.38, p = 0.944) or severe AE (OR 1.673, 95% CI 0.93–3.00, p = 0.085). Treatment with second-line immunotherapy was associated with higher final mRS scores in sub-groups with LGI-1 AE (OR 6.70, 95% CI 1.28–35.1, p = 0.024) and long-term follow-up (OR 3.94, 95% CI 1.67–9.27, p = 0.002).
Discussion We did not observe an association between treatment with second-line immunotherapy and lower final mRS scores in patients with treated AE. This result should be interpreted with caution given the risk of bias, limited adjustment for disease severity and treatment timing, and insensitivity of the mRS in estimating psychiatric and cognitive disability.
