Natalizumab Sets Itself Apart From Other MS Treatments


Carrie Hersh, DO, MSc, assistant professor of neurology at the Cleveland Clinic Lerner College of Medicine, discusses recent data on natalizumab as well as what sets it apart from other multiple sclerosis treatments.

Carrie Hersh, DO, MSc

Carrie Hersh, DO, MSc

Data presented at the 2020 Consortium of Multiple Sclerosis Centers (CMSC) Virtual Annual Meeting from 2 studies of natalizumab (Tyasbri; Biogen) demonstrated the multiple sclerosis (MS) treatment’s significant impact on the “feel-good” experience for patients, as well as the lower cumulative probability of no disease activity when switching off to a moderate disease modifying therapy (DMT).

Natalizumab, FDA-approved for the treatment of relapsing forms of MS, showed a significantly higher number of patients who felt good while on the therapy (n = 95; 63%) compared with other DMT-treated patients (45%; n = 252; P = .001). Additionally, 78% of natalizumab-treated patients self-reported physical benefits compared with 67% of other DMT patients (P = .017).

In the second study, led by Carrie Hersh, DO, MSc, neurologist, Cleveland Clinic Lou Ruvo Center for Brain Health, patients who switched to moderate DMTs had higher proportions with new T2 lesions (odds ratio [OR], 2.15; 95% CI, 1.18—3.01; P = .011), new gadolinium-enhancing (GdE) lesions (OR, 1.99; 95% CI, 1.12—2.73; P = .022), and 20% worsening of the Timed 25-Foot Walk test (OR, 1.83; 95% CI, 1.06—3.02; P = .043) and 9-Hole Peg Test (OR, 1.81; 95% CI, 1.05—3.56; P = .044) compared with a switch to high-efficacy therapy (HET).

Since its approval in 2004, the agent has been tested in numerous studies, ranging across varying objectives in multiple types of the central nervous system disease. NeurologyLive discussed the 2 most recent studies with Hersh, and her overall thoughts on 1 of the most prominent drugs in the MS community.

NeurologyLive: What are you overall thoughts on switching strategies for patients transitioning off natalizumab?

Carrie Hersh, DO: Understanding the implications of DMT sequencing—whether it is related to safety or breakthrough disease on a particular therapy—is a paramount aspect of long-term MS management. This facet of care is particularly important following natalizumab cessation due to the risk of rebound disease that can lead to irreversible disability. Previous studies indicated that switching from natalizumab to lower-effective therapies (e.g. glatiramer acetate, interferon beta) lead to poorer MS disease outcomes. Our study investigating the comparative effectiveness of switching to moderate-efficacy DMT (e.g. dimethyl fumarate, fingolimod) vs. high-efficacy DMT (e.g. alemtuzumab, ocrelizumab, rituximab) resulted in worse disease activity and progression measures. In this context, our study suggested that patients fare better when transitioning from one high-efficacy DMT to another, especially when discontinuing natalizumab due to breakthrough disease. These results align with real-world experience in a broader sense.

What do clinicians need to be mindful of when transitioning patients on natalizumab?

Crucial aspects of natalizumab transition are washout duration and the choice of DMT. Numerous studies have demonstrated that shorter washout periods, at least < 3 months from natalizumab discontinuation before risks of rebound disease occur, lead to fewer relapses and new MRI activity.

As our current investigation showed, patients who switched from natalizumab to another high-efficacy DMT overall fared better in terms of early disease activity (6 months post-natalizumab) and longer-term outcomes (24 months post-natalizumab). Certain safety concerns, such as progressive multifocal leukoencephalopathy (PML) risk, also need to be considered when switching from natalizumab, for which a surveillance brain MRI in between therapies is recommended for mitigation purposes.

One study reported benefits for physical, emotional, and cognitive domains for patients on natalizumab; how important are these components when selecting therapy for patients?

Patient reported outcomes (PROs) are crucial measures in understanding the patient perspective on their perception of functional well-being and health status. Recognizing the impact of a particular DMT on patients’ overall quality of life is incredibly important in their long-term care, which also impacts treatment adherence. To this effect, PROs have now become important secondary outcome measures in pivotal clinical trials and other observational studies. Multiple studies have now shown that patients treated with natalizumab are less depressed and overall have better quality of life, as it relates to the robust anti-inflammatory effects of this highly efficacious DMT.

Transcript edited for clarity.


1. Foley J, Berkovich R, Gudesblatt M, et al. Natalizumab-treated patients with relapsing-remitting multiple sclerosis report better “feel-good” outcomes in key physical, emotional, and cognitive domains compared to other disease-modifying therapies. Int J MS Care. 2020;22(2 Suppl).

2. Hersh CM, Harris H, Conway D, Hua LH. Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice. Neurology Clin Pract. Published online February 12, 2020, doi:

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