Switch from Tysabri to Ocrevus Seen as Safe, Effective in RRMS Patients in Small Study

Switching to Ocrevus (ocrelizumab) within a relatively short period is a safe and effective option for people with relapsing-remitting multiple sclerosis (RRMS) who stop treatment with Tysabri (natalizumab), a small and retrospective analysis suggests.

With a median washout period of six weeks between therapies, the 28 patients in this study had no relapses and there were no reports of progressive multifocal leukoencephalopathy (PML), a viral disease that sometimes occurs in Tysabri-treated patients due to low immune cell numbers in the brain.

The study, “Switching from natalizumab to ocrelizumab in patients with multiple sclerosis,” was published as a letter in the Multiple Sclerosis Journal.

Tysabri (marketed by Biogen) is an antibody-based disease-modifying therapy (DMT) that lowers brain inflammation in RRMS patients by preventing immune cells from entering the brain.

But Tysabri is associated with an increased risk of developing PML, a rare and often fatal viral disease caused by the John Cunningham virus (JCV). PML progressively damages the protective myelin sheath that insulates nerve cells.

A lesser migration of immune cells into the brain with Tysabri’s use is thought to be the reason for this increased PML risk, as not enough immune cells exist to fight the opportunistic infection.

To minimize this infection risk, particularly in people carrying antibodies against the JC virus who are at highest PML risk, patients may opt to switch to a different DMT, such as Ocrevus. But washout periods, which may span two or more months between treatments, can increase disease activity and prompt relapses.

Some MS patients also appear sensitive to “carryover” PML — PML that develops a few months after stopping a DMT associated with this viral disease, and starting a different DMT. This would include switching from Tysabri to Ocrevus.

Ocrevus is a monoclonal antibody developed by Genentech, a subsidiary of Roche, that targets the CD20 protein found on the surface of immune B-cells. These cells are believed to target the nerve fibers and myelin sheaths of healthy neurons, triggering multiple sclerosis (MS) onset and progression.

To assess the safety and efficacy of their hospital’s protocol for a Tysabri to Ocrevus transition, researchers at Columbia University Irving Medical Center retrospectively examined data from 28 patients followed at their center, who made this switch between March 2017 and May 2019.

These people were 40 years old on average, and most (75%) were women. Their symptoms had started about eight years before discontinuing Tysabri, and they had received a median of 36 Tysabri infusions. For about one-third (36%), Tysabri was their first DMT.

PML risk was the most common reason given for switching from Tysabri to Ocrevus (18 patients). Others included a transition to secondary progressive MS (five patients), fewer infusions (every four weeks with Tysabri, every six months with Ocrevus; 4 patients), and pregnancy planning (one patient).

Seventeen of these patients tested positive for antibodies against JCV, and four had high antibodies titers (greater than 1.5). All 17 underwent MRI brain scans before starting on Ocrevus, and one also was tested for PML via a sample of cerebrospinal fluid — the liquid surrounding the brain and spinal cord — after new, non-enhancing T2 lesions were found on an MRI.

The average washout period between therapies was 44 days, or about six weeks, and no relapses occurred during the transition, the researchers wrote.

New, non-enhancing T2 lesions were seen on MRIs of four patients taken about six months after a first Ocrevus treatment, but all these lesions seemed related to MS progression rather than “washout time” for the transition, the researchers wrote. One progressive MS patient also experienced a worsening in disability scores.

After a median follow-up of 22 months, no serious infections, including PML, were found in any of these 28 people.

“A standardized approach to natalizumab cessation is currently lacking, although experts recommend a short washout period to reduce disease activity. Therefore, the absence of relapses in our cohort may partly derive from the median 6-week transition window,” the researchers wrote.

“Our analysis suggests that ocrelizumab is an effective and reasonably safe option for patients who stop natalizumab,” they added. “We observed no cases of carryover PML.”

Still, the researchers recommend that additional studies in larger populations are needed confirm these results.