Rituximab and IVIG added to plasma exchange improves the outcome of severe CNS demyelinating attacks: a retrospective study

Background: Plasma exchange (PE) is a therapeutic option for CNS demyelinating attacks unresponsive to corticosteroids, but the potential benefit of adding rituximab and IV immunoglobulins to PE (RTX-IVIG-PE), which has shown its efficacy and safety in other immune-mediated conditions, has not been investigated. Objective: We aimed to determine the overall effectiveness of PE in severe demyelinating attacks, identify predictors of response, and compare outcomes between standard PE and RTX-IVIG-PE protocols. Design: Retrospective analysis of patients with CNS demyelinating attacks treated with PE between 2012 and 2023 across five Spanish hospitals. Methods: Clinical response was measured as an improvement or a complete recovery at discharge and 6 months. Uni- and multivariable logistic regression models were developed to identify predictors of PE response. A logistic regression analysis, after inverse probability of treatment weighting (IPTW), was performed to compare the outcome of attacks treated with standard PE and RTX-IVIG-PE. Results: A total of 162 attacks in 150 patients (81 multiple sclerosis; 37 others acquired demyelinating syndromes; 27 neuromyelitis optica spectrum disorder; 5 myelin oligodendrocyte glycoprotein antibody-associated disease; 73% female; median age 43 years (interquartile range 33–52.75)) were analyzed. At discharge, 60% of all attacks showed clinical improvement, and 15% achieved complete recovery. At 6 months, these rates increased to 77% and 31%, respectively. Younger age, lower preattack Expanded Disability Status Scale, and treatment with RTX-IVIG-PE were independent predictors of complete recovery at 6 months. IPTW analysis showed that attacks treated with RTX-IVIG-PE (33) were associated with improvement (adjusted odds ratio (aOR) 5.4, p < 0.001) and complete recovery (aOR 4.55, p < 0.001) at 6 months compared to those treated with standard PE (129), without significant differences in the adverse event profile between the two protocols. Conclusion: PE improves the outcome of steroid-refractory CNS demyelinating attacks, and the addition of rituximab and IVIG to PE may increase the likelihood of long-term recovery.