Mechanism, Indications, and Clinical Evidence
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. While most MS relapses respond to high-dose corticosteroids, a subset of patients experience steroid-refractory relapses—episodes that do not improve with standard treatment. In these cases, Therapeutic Plasma Exchange (TPE) has emerged as a valuable second-line therapy, capable of removing pathogenic antibodies and immune complexes that drive inflammation¹.
At AgeReversalMD, Dr. Phillip Milgram, MD offers TPE for patients with MS who meet specific clinical criteria. This article outlines the mechanism of TPE, its role in MS management, and the evidence supporting its use.
How TPE Works in MS
TPE involves the removal and replacement of plasma—the liquid portion of blood that contains antibodies, cytokines, and other immune mediators. During the procedure:
- Blood is drawn from the patient
- Plasma is separated and discarded
- A replacement fluid (usually albumin) is infused
- Blood cells are returned to the body
In MS, especially during acute relapses, TPE helps by removing circulating autoantibodies that target myelin and other neural components. This reduces inflammation and allows the central nervous system to begin repair².
When Is TPE Used in MS?
TPE is not a first-line treatment for MS but is recommended in specific scenarios:
- Corticosteroid-refractory relapses: When symptoms persist despite IV methylprednisolone
- Severe optic neuritis: Especially when vision loss is profound and unresponsive to steroids
- Clinically isolated syndrome (CIS): In select cases with aggressive onset
- Tumefactive MS lesions: Large inflammatory lesions that mimic tumors
According to the American Society for Apheresis (ASFA), TPE for MS is classified as a Category II, Grade 1B indication—meaning it is a second-line therapy with moderate to strong evidence³.
Clinical Evidence Supporting TPE in MS
Several studies have demonstrated the efficacy of TPE in steroid-refractory MS relapses:
- A multicenter study found that up to 70% of patients with steroid-resistant relapses showed clinical improvement after TPE⁴
- Improvement typically begins after the second or third exchange, with gains in motor function, vision, and sensory symptoms
- TPE is especially effective in relapses with MRI evidence of active inflammation, such as gadolinium-enhancing lesions⁵
In a 2025 review published in Biomedicines, researchers concluded that TPE is a “mechanistically sound and clinically effective” intervention for selected MS patients, particularly when initiated early in the relapse course⁶.
Protocol and Treatment Course
The standard TPE protocol for MS involves:
- Five to seven exchanges over 10 to 14 days
- Each session removes approximately 1 to 1.5 plasma volumes
- Replacement fluid is typically 5% albumin
- Monitoring includes vital signs, calcium levels, and hematologic parameters
Patients are evaluated before and after treatment using neurological scales such as the Expanded Disability Status Scale (EDSS) and visual acuity testing.
Safety and Tolerability
TPE is generally well tolerated. Common side effects include:
- Mild hypotension
- Fatigue
- Hypocalcemia (managed with calcium supplementation)
- Risk of infection (if central venous access is used)
Serious complications are rare but may include allergic reactions, bleeding, or cardiac arrhythmias. At AgeReversalMD, Dr. Milgram’s team follows strict protocols to ensure safety and comfort throughout the procedure⁷.
TPE vs. IVIG in MS
While IVIG is used in other autoimmune conditions, it is not routinely recommended for MS relapses. TPE is preferred in steroid-refractory cases due to its ability to rapidly remove pathogenic antibodies, whereas IVIG works by modulating immune response over time.
| Feature | TPE | IVIG |
|---|---|---|
| Mechanism | Removes autoantibodies | Modulates immune activity |
| Onset of effect | Rapid (2–3 sessions) | Gradual (days to weeks) |
| Use in MS | Steroid-refractory relapses | Not standard for MS relapses |
Long-Term Impact and Follow-Up
TPE is not a disease-modifying therapy (DMT) for MS. It does not prevent future relapses or slow progression. Instead, it is used to manage acute episodes and restore function when standard treatments fail.
After TPE, patients typically resume or adjust their DMT regimen, which may include:
- Interferon beta
- Glatiramer acetate
- Natalizumab
- Ocrelizumab
- Oral agents such as fingolimod or dimethyl fumarate
Dr. Milgram works closely with neurologists and immunologists to coordinate long-term care and ensure continuity of treatment.
Conclusion
Therapeutic Plasma Exchange is a proven second-line therapy for patients with Multiple Sclerosis experiencing steroid-refractory relapses. By removing circulating immune factors that drive inflammation, TPE offers rapid symptom relief and functional recovery. At AgeReversalMD, Dr. Phillip Milgram, MD provides personalized TPE protocols for MS patients who meet clinical criteria—helping them regain control and move forward with confidence.
References
- Padmanabhan, A., Connelly-Smith, L., Aqui, N., Balogun, R. A., Klingel, R., Meyer, E., … & Schwartz, J. (2019). Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the Writing Committee of the American Society for Apheresis: The eighth special issue. Journal of Clinical Apheresis, 34(3), 171–354. https://doi.org/10.1002/jca.21705
- Marrodan, M., Ysrraelit, M. C., & Correale, J. (2025). Therapeutic plasma exchange in corticosteroid-refractory multiple sclerosis relapses: Mechanisms, efficacy, and integration into clinical practice. Biomedicines, 13(10), 2399. https://doi.org/10.3390/biomedicines13102399
- Schwartz, J., Padmanabhan, A., Aqui, N., Balogun, R. A., Connelly-Smith, L., Delaney, M., … & Witt, V. (2016). Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the Writing Committee of the American Society for Apheresis: The seventh special issue. Journal of Clinical Apheresis, 31(3), 149–162. https://doi.org/10.1002/jca.21470
- Stasiolek, M. (2015). Therapeutic plasma exchange in MS relapses. European Multiple Sclerosis Platform. https://emsp.org/wp-content/uploads/2015/05/16052015-Therapeutic-Plasma-Exchange-in-MS_Stasiolek.pdf
- HealthCentral. (2024). Plasma exchange for MS: Benefits, risks, and efficacy. https://www.healthcentral.com/article/therapeutic-plasma-exchange-for-ms
- Correale, J., Marrodan, M., & Ysrraelit, M. C. (2025). Mechanisms of action and clinical utility of TPE in MS. Biomedicines, 13(10), 2399.
- Nature Scientific Reports. (2022). Therapeutic plasma exchange in multiple sclerosis patients with an inadequate response to corticosteroids. https://www.nature.com/articles/s41598-022-23356-w.pdf