Ocrevus best to prevent MS relapses after stopping Tysabri: Study

Ocrevus (ocrelizumab) — given by infusion — may work better than certain oral treatments to prevent relapses and disability worsening in people with relapsing-remitting multiple sclerosis (RRMS) who transition from Tysabri (natalizumab), a new study found.

Individuals who switched to Ocrevus also were more likely to stay on treatment than those who started taking the oral therapies — namely Gilenya (fingolimod) and Tecfidera (dimethyl fumarate). Those patients were found to be more likely to discontinue therapy than were individuals on Ocrevus, with the most common reason being a lack of effectiveness with the oral medications.

According to researchers, these findings can help inform treatment decision-making for multiple sclerosis (MS) patients who need to stop using Tysabri due to lack of efficacy or side effects.

“If patients need to change their medication from [Tysabri], which is highly effective in treating MS, it can be an anxious and distressing time. Our study helps neurologists and patients make a better informed choice,” Helmut Butzkueven, PhD, a neurologist and professor at Monash University in Australia, and the study’s senior author, said in a university press release.

The study, “Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation,” was published in JAMA Neurology.

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High risk of relapse for patients stopping Tysabri

An approved disease-modifying therapy (DMT), Tysabri is given intravenously (into the vein) for people with relapsing forms of MS. It’s proven to be highly effective at preventing disease relapses, disability progression, and the formation of new lesions.

However, Tysabri is associated with an increased risk of progressive multifocal leukoencephalopathy or PML, a rare but life-threatening brain infection caused by the John Cunningham virus (JCV).

As such, the treatment is only available to patients in the U.S. through a restricted distribution program. Many other countries have monitoring requirements for people using Tysabri.

Patients typically are tested for anti-JCV antibodies — a sign that the body has been exposed to the virus — during regular blood tests. Individuals testing positive are often required to discontinue the treatment and switch to an alternative one.

Tysabri cessation, however, is associated with a particularly high risk of relapse, so the appropriate choice of a replacement therapy is critical.

Still, it is not definitively established which alternative is best for preventing disease activity in these patients.

To find out, a global team of researchers retrospectively reviewed clinical outcomes among RRMS patients who switched to either Ocrevus, Gilenya, or Tecfidera after stopping Tysabri. Data were obtained from the MSBase registry, an international observational study tracking outcomes for nearly 90,000 MS patients. Here, the patient information was collected between June 2010 and July 2021.

Participants were included if they had taken Tysabri for at least six months before its discontinuation, switched to an alternative within three months, and then used their new treatment for at least six more months.

A total of 1,386 patients, 71% of whom were women, met this criteria. Their mean age was 41.3. Nearly 60% (823 patients) switched to Gilenya, while about 10% (138) switched to Tecfidera and about 30% (425) changed to Ocrevus.

Patients in the Tecfidera group had the oldest mean age, whereas those on Gilenya had the youngest. Patients with higher relapse rates in the previous year were more likely to receive Gilenya and least likely to receive Tecfidera.

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The main goal of the study was to evaluate annualized relapse rates — known as ARR — following the switch. After adjusting the data to account for differences in the three groups at the study’s start, the results showed that patients who switched to Ocrevus experienced a mean of 0.06 relapses per year. That was significantly lower than the 0.26 relapses per year on Gilenya, and the 0.27 relapses per year on Tecfidera.

Overall, Ocrevus reduced relapse rates by more than four times compared with the other two treatments. It also reduced the risk of experiencing a first relapse by about four times.

Our findings can help inform subsequent DMT selection [after stopping Tysabri].

Ocrevus was associated with a 49% lower risk of sustained disability progression relative to Gilenya, as assessed by the Expanded Disability Status Scale (EDSS). A comparison could not be made with those on Tecfidera, as there were too few people in that group experiencing disability progression.

Following the switch, the most common reason for stopping Gilenya or Tecfidera treatment was a lack of efficacy, reported in 48% and 31% of those groups, respectively. In contrast, the most common reason for stopping Ocrevus was side effects, cited by 35% of patients.

Gilenya-treated patients were less likely to stop treatment than those on Tecfidera.

But individuals in both the Gilenya and Tecfidera  groups were significantly more likely to discontinue treatment over time than those on Ocrevus.

Overall, “[Ocrevus] is a better choice of switch DMT after [Tysabri] cessation,” the researchers wrote, which could be related to the “intrinsic superiority” of its mechanism in controlling disease activity.

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Gilenya works similarly to Tysabri — both prevent immune cells from gaining access to the brain and launching an inflammatory attack — while Tecfidera dampens inflammation by changing the activity of immune cells.

Ocrevus specifically depletes immune B-cells, which are responsible for producing antibodies that drive autoimmunity. Still, the observational nature of the study doesn’t allow for the determination that this specific mechanism is best during a therapy switch, according to the scientists.

Importantly, the team noted that MSBase does not contain specific safety data related to use of DMTs, which would be a key factor in guiding clinical decision-making in choosing a treatment.

Nevertheless, “our findings can help inform subsequent DMT selection” for patients stopping Tysabri, the team concluded.