Anti-CD20s effective MS therapy switch from Tysabri: Review

Study may inform future switch protocol guidelines, researchers say

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Switching to one of the anti-CD20 targeting therapies Ocrevus (ocrelizumab) or rituximab may be an effective strategy for discontinuing Tysabri (natalizumab) treatment in multiple sclerosis (MS) patients at risk for progressive multifocal leukoencephalopathy (PML), according to a systematic review.

The study, “Switching from natalizumab to an anti-CD20 monoclonal antibody in relapsing remitting multiple sclerosis: A systematic review,” was published in Multiple Sclerosis and Related Disorders.

PML is a severe brain infection that causes loss of myelin, the protective coating around nerve fibers that is key for proper nerve cell communication. In MS, the immune cells that drive an attack against the myelin sheath must cross through the blood-brain barrier to get into the central nervous system (CNS), which consists of the brain and spinal cord.

Tysabri is an antibody-based therapy that works to prevent the entry of immune cells into the CNS. It has been shown to reduce relapse rates and slow disability progression in people with relapsing forms of MS — including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS.

The treatment is associated with an increased risk of PML, but may be used for short-term disease control in patients positive for the John Cunningham virus, which causes the infection. However, discontinuing treatment should only occur when there is a clear plan to switch to another therapy, to prevent disease reactivation.

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Potential switch protocol

“Overall, this [systematic review] provides a foundation for future consensus guidelines regarding a switch protocol in patients at risk of PML transitioning from [Tysabri] to [CD20 antibodies],” the researchers wrote.

They analyzed available evidence on switching from Tysabri to anti-CD20 antibody-based treatments, which target the CD20 protein on the surface of mature B-cells, the cells responsible for antibody production.

Five observational studies published from 2016 to 2022 were included in the analysis. The studies contained data from 331 patients across several European countries, 68% of whom were women. Patients had a mean age of 40.6, had been living with MS for a mean of 10.8 years, and were on Tysabri for a mean of 4.6 years.

Across the five studies, all or almost all participants had the John Cunningham virus.

There were variations across studies regarding the intervals between Tysabri dosing regimens before discontinuation. In some studies, patients remained on the standard interval dosing of every four weeks, while in others that interval was extended.

The washout period, defined as the time elapsed between the last Tysabri infusion and the first infusion of a CD20 antibody, ranged from 4.4 weeks to 10.7 weeks. No patients experienced a clinical MS relapse or PML during that period.

Overall, 181 patients (55%) switched to Ocrevus, while 150 (45%) switched to rituximab, a therapy used off-label for MS. After the switch, the incidence (new cases) of MS relapse ranged from 1.8% to 10% during follow-up, with a mean of 8.8% at one year.

In three studies with available data, the annualized relapse rate ranged from 0.02 and 0.12, with a mean of 0.07. The overall incidence of PML within six months of follow-up was 0.6%.

The incidence of new active brain lesions detected by MRI ranged from zero to 12%. Worsening of disease disability, measured by the Expanded Disability Status Scale, ranged from zero to 9.5%.

“Our results indicate that [anti-CD20 therapies] are a suitable transitional option for patients who discontinue [Tysabri], with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse,” the researchers concluded.

Although the most appropriate washout period is still unclear, it “is likely between 4 and 12 weeks,” they wrote.