Ocrevus keeps MS activity stable after stopping Tysabri: Study
Phase 4 OCTAVE trial focused on people with relapsing forms of MS
Switching from Tysabri (natalizumab) to Ocrevus (ocrelizumab) does not appear to increase disease activity in people with relapsing forms of multiple sclerosis (MS) and stable disease, with most patients continuing to show no relapses or brain imaging findings one year after the transition, a clinical study shows.
Tysabri is known to increase the risk of progressive multifocal leukoencephalopathy (PML), a rare and potentially life-threatening brain infection, especially after two years of treatments. The findings suggest that Ocrevus may be a safe and effective treatment for people who choose to discontinue Tysabri, either because of concerns about PML or due to other factors.
The study, “Evaluating the efficacy and safety of transitioning patients with multiple sclerosis from natalizumab to ocrelizumab (OCTAVE),” was published in the Multiple Sclerosis Journal.
In MS, inflammation destroys the protective myelin sheath surrounding nerves, leading to a faulty communication between nerve cells and nerve cell damage. Its symptoms may get worse over the years or change in phases where attacks (relapses) follow periods of stable symptoms (remissions).
An approved disease-modifying therapy, Tysabri eases inflammation and the resulting nerve damage, thereby reducing the number of relapses and the worsening of disability. However, it is available in the U.S. only through a restricted distribution program.
This is because its use increases the risk of a serious brain infection called PML that is caused by John Cunningham virus (JCV). The risk is even higher for those treated with Tysabri for more than two years.
The risk “led to discontinuation of [Tysabri] in many patients and limited its use for the treatment of MS,” the researchers wrote. “Unfortunately, stopping [Tysabri] increases the risk of MS reactivation, even when switching to another disease modifying therapy.”
Recent data showed that switching to Ocrevus, a Genentech medication given as an infusion into the vein, may work better than certain oral therapies at preventing relapses in patients who stopped Tysabri.
OCTAVE trial results
Now, researchers shared data from a Phase 4 study, called OCTAVE (NCT03157830), which assessed how safe Ocrevus is and how it affects disease activity in people who discontinued Tysabri.
The trial, conducted in collaboration with Genentech, enrolled 43 patients who had received a stable dose of Tysabri for 12 months or more and who had not experienced a relapse, MRI activity, or disability worsening six months prior to the switch.
Participants, ranging in age from 20 to 64 years, had received a median 47 infusions of Tysabri and were switched to Ocrevus 4-6 weeks after their last Tysabri dose.
A total of 33 (77%) patients tested positive for anti-JCV antibodies in blood, indicating an increased risk of PML, and 35 (81%) switched to Ocrevus due to concerns about this risk with the continued use of Tysabri.
After a median of 12.4 months on Ocrevus, two patients experienced a relapse. Both experienced symptoms of leg weakness, but while one had no worsening in disability, the other lost the ability to complete a 500 meter (546 yards) walk. None of these patients showed changes on brain MRI scans.
Two other patients showed both MRI activity, either as new lesions with active inflammation or lesions of permanent nerve damage (known as black holes). However, they did not experience any new symptoms during the course of the study.
‘No discernible new disease activity’
Overall, “most patients who transitioned from [Tysabri] to [Ocrevus] experienced no discernible new disease activity,” the researchers wrote. The two patients who had a relapse “lacked objective changes on imaging; as a result, their presentations were more likely consistent with a pseudo-relapse,” they added.
None of the patients developed PML. There were 13 serious side effects in eight (18.6%) patients, occurring a median of 201 days (about six months) after the switch to Ocrevus.
Of the serious side effects, “four were possibly related to [Ocrevus] and included a case of breast cancer, a spontaneous abortion, and two cases of serious urinary tract infections,” the researchers wrote.
The data suggests that most patients who switch from Tysabri to Ocrevus show stable symptoms and brain MRI findings, but it is important to monitor them for possible serious side effects.
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