Functional outcomes of patients with NORSE and FIRES treated with immunotherapy: A systematic review

Objective

To determine the frequency of good functional outcomes in patients with NORSE and FIRES treated with immunotherapy.

Methods

We performed a systematic search of the MedLine and EMBASE databases to gather studies including at least 5 patients with NORSE or FIRES and at least one patient treated with immunotherapy, and reporting functional outcomes. Good functional outcome was defined as a modified Rankin Scale (mRS) score ≤ 2 (or an equivalent measure) at the last available follow-up assessment. Only patients with known functional outcomes were included in the analysis.

Results

We analyzed 16 studies including a total of 161 patients with NORSE. Six studies were carried out only with FIRES patients (n = 64). Of the 161 patients with NORSE, 141 (87.5%) received immunotherapy. Outcome data were available for 135, 56 of whom (41.4%) achieved good functional outcomes. Twenty-four of the 58 patients with FIRES treated with immunotherapy and for whom outcome data were available achieved good functional outcomes (41.3%). Mortality rates in patients with NORSE and FIRES treated with immunotherapy were 20/121 (16.5%) and 6/58 (10.3%), respectively. By type of immunotherapy, good functional outcomes were achieved in 36/89 patients receiving glucocorticoids (40.4%), 27/71 patients receiving IV immunoglobulins (38%), 11/37 patients treated with plasma exchange (29.7%), 5/17 patients receiving rituximab (29.4%), and 2/13 patients receiving cyclophosphamide (15.3%).

Conclusion

Despite the lack of randomised clinical trials, immunotherapy is frequently prescribed to patients with NORSE and FIRES. However, rates of functional dependence and mortality remain high in these patients. Second-line therapies achieved lower rates of good outcomes, probably because they were administered to patients with more severe, refractory disease.