# Therapeutic Plasma Exchange in Corticosteroid-Refractory Multiple Sclerosis Relapses: Mechanisms, Efficacy, and Integration into Clinical Practice

## TL;DR

Therapeutic plasma exchange helps some multiple sclerosis patients who don't respond to steroids by removing harmful immune substances.

## Contribution

The paper provides a comprehensive review of TPE mechanisms, efficacy, and clinical integration for corticosteroid-refractory MS relapses.

## Key findings

- 40–60% of patients show moderate-to-marked functional improvement with TPE.
- Best outcomes occur when TPE is initiated within 14 days of symptom onset.
- Predictors of response include young age, short disease duration, and specific neurological involvement.

## Abstract

Therapeutic plasma exchange (TPE) is increasingly recognized as a critical escalation therapy for managing acute multiple sclerosis (MS) relapses refractory to high-dose corticosteroids. Neuropathological and clinical evidence implicate humoral immune mechanisms, particularly autoantibodies, immune complexes, and complement activation, as key pathogenic drivers in a subset of MS attacks, notably those consistent with immunopathological pattern II. By removing these circulating immune effectors, TPE provides a rational strategy to dampen inflammation and promote neurological recovery. This review integrates current mechanistic insights with clinical efficacy data and practical implementation strategies for TPE in corticosteroid-refractory MS. Evidence from randomized controlled trials and observational cohorts demonstrates moderate-to-marked functional improvement in 40–60% of patients, with the greatest benefit observed when therapy is initiated within 14 days of symptom onset and cases demonstrating active inflammatory lesions on MRI. Predictors of a favorable response include younger age, short disease duration, severe syndromes involving optic nerve, brainstem, or spinal cord, and CSF markers of intrathecal B-cell activity. Although TPE is generally well tolerated in experienced centers, its broader adoption of TPE is limited by variability in access, institutional protocols, and provider familiarity. Standardization of treatment algorithms, validation of predictive biomarkers, and incorporation into streamlined clinical pathways are critical to maximizing its clinical impact. Future priorities include comparative trials against alternative escalation therapies, biomarker-guided patients’ selection, and comprehensive health-economic evaluations. Taken together, current evidence and recommendations from major neurology and apheresis societies support TPE as a valuable therapeutic modality capable of significantly improving relapse outcomes in appropriately selected MS patients.