Switching to Ocrevus Over Other MS Therapies Means Fewer Relapses

People with relapsing-remitting multiple sclerosis (RRMS) who switch to Ocrevus (ocrelizumab) after discontinuing Gilenya (fingolimod) have fewer relapses than those who switch to Mavenclad (cladribine) or Tysabri (natalizumab), according to a new study.

Rates of disability worsening were similar for Ocrevus and Tysabri, but patients who switched to Tysabri were more likely to report disability improvements, or less disability, after switching than those on Ocrevus.

“Specialists are not sure what is the optimal treatment to provide patients with MS when they need to discontinue [Gilenya]. Now, we can use the knowledge from our study to inform their practice and help patients receive the most benefit in terms of their disease,” Helmut Butzkueven, PhD, a professor at Monash University and co-author of the study, said in a university press release.

The study, “Comparing switch to ocrelizumab, cladribine or natalizumab after fingolimod treatment cessation in multiple sclerosis,” was published in the Journal of Neurology, Neurosurgery & Psychiatry. It was not funded by any specific source, but many of the authors disclosed having received funding from various pharmaceutical companies in the past.

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November 23, 2022 News by Marisa Wexler, MS

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There are more than a dozen approved treatments for RRMS, which have been proven in clinical trials to slow the progression of symptoms and reduce rates of relapses. Over the course of their disease journey, many patients will switch between multiple therapies for reasons such as side effects, lack of effectiveness, or planning for pregnancy.

There’s generally little published data on how outcomes differ for switching. An international team led by scientists in Australia analyzed data from the MSBase registry, an international observational study initiated in 2004 that stores clinical and demographic data from MS patients who switched from Gilenya to either Ocrevus, Mavenclad, or Tysabri.

Gilenya is a once-a-day oral therapy that works by “trapping” immune cells inside lymph nodes so they can’t get into the nervous system and cause MS-driving inflammation. Mavenclad is a short-course oral treatment that kills several types of inflammation-driving immune cells. Ocrevus and Tysabri are both administered via infusion. Ocrevus kills B-cells and Tysabri stops immune cells from entering the nervous system.

Comparing MS therapies’ annual relapse rates

The study included data from 1,045 RRMS patients from 26 countries. All had been on Gilenya for at least six months and then switched to one of the other therapies within three months of stopping it. Specifically, 445 switched to Ocrevus, 76 to Mavenclad, and 524 to Tysabri.

Only those on the switch therapy for at least six months were included in the analyses. Disability scores were similar in all three groups, though the Tysabri group tended to be younger with a shorter disease duration. The median follow-up time in all the groups was more than a year.

Over the course of follow-up, the annualized relapse rate (ARR) with Ocrevus was 0.07 relapses a year. The ARR for Mavenclad was 0.25 relapses a year, and for Tysabri it was 0.11 relapses per year.

Overall relapse rates tended to be lower for patients on Ocrevus than Tysabri, with patients on Ocrevus about 43% less likely to experience a first relapse, statistical tests showed. Relapse rates were lower for Tysabri than Mavenclad, though risk of first relapse did not differ significantly between the two.

The apparently better effectiveness of Ocrevus compared with Tysabri in patients who stopped Gilenya may be explained by how these therapies work, the researchers noted. Gilenya and Tysabri both broadly interfere with the movement of immune cells, whereas Ocrevus kills immune cells.

Nonetheless, the team noted that “relapse rates in all treatment groups were relatively low, suggesting that all these three DMTs are feasible and reasonable treatment options.”

Tysabri shows more disability improvement

Rates of disability worsening were similar among patients on Ocrevus or Tysabri. However, those on Tysabri were 51% more likely to report disability improvement after switching and this change lasted through the end of follow-up in most of these patients. Mavenclad was not included in disability comparisons due to the low number of patients.

“Our results comparing [Ocrevus] to [Tysabri] appear to be inconsistent. However, we do not consider these results to be contradictory,” the researchers wrote, noting that improved disability usually reflects repair in the nervous system, whereas relapses are indicative of new damage. “These mechanisms could easily be differentially affected by the different mechanisms of action” of the two therapies.

Patients on Ocrevus were 89% less likely to stop that treatment compared to those on Tysabri and discontinuation rates were comparable between Tysabri and Mavenclad. The most common reason for discontinuing the two latter treatments was scheduled stop, whereas most patients who stopped Ocrevus did so because of side effects.

“In patients with RRMS who discontinue [Gilenya] and commence another disease-modifying treatment within 3 months, [Ocrevus] was associated with a significant reduction in [relapse rates], longer time to first relapse and a lower discontinuation rate compared with [Mavenclad] and [Tysabri]. [Tysabri] was associated with better sustained disability improvement compared with [Ocrevus],” the researchers concluded.