MS symptoms can fluctuate with Ocrevus, but ‘wearing off’ not likely

Disease's 'natural' variability seen as likely cause of shifts between infusions

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A person lays on a gurney while being given an IV infusion.

People with multiple sclerosis (MS) under treatment with Ocrevus (ocrelizumab) commonly experience fluctuations in the severity of their symptoms — but these changes aren’t related to the timing of Ocrevus infusions, a study reports.

Although many patients on Ocrevus report a ‘wearing off’ effect between infusions, findings suggest that these experiences are caused by the natural variability of MS symptoms, rather than any direct biological effect with the medication.

“The common perception of wearing off is probably mostly due to natural fluctuations in MS symptoms, which are liable to be attributed to ‘wearing off of the drug’ when they coincide with the time for reinfusion,” the researchers wrote.

The study, “No Increase in Symptoms Toward the End of the Ocrelizumab Infusion Cycle in Patients With Multiple Sclerosis,” was published in Neurology Clinical PracticeThe work was supported by a grant from Genentech, a subsidiary of Roche, which markets Ocrevus.

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Patients report changes in MS symptom severity between Ocrevus infusions

Ocrevus is an approved treatment for relapsing types of MS and for primary progressive MS. The therapy works by killing B-cells, a type of immune cell that causes disease-driving inflammation in the brain and spinal cord.

It is administered via infusion into the bloodstream. After two loading doses given two weeks apart, infusions of the therapy are given every six months.

Some people have reported experiencing a ‘wearing off’ effect between doses of Ocrevus, but it’s been unclear whether this is a consistent biological phenomenon. Scientists at NYU Grossman School of Medicine in New York conducted an observational study (NCT04855617) to gain greater insight.

In the study, 103 MS patients on Ocrevus completed a battery of assessments of symptom severity at three time points: right after an infusion of Ocrevus, about midway between infusions, and just before the next infusion. Most also completed the assessments for a second six-month cycle of Ocrevus treatment.

Patients’ mean age was 46.49, with 67% identifying as white, 17% as Black, and 14% as Hispanic or Latino.

Once assessment data were collected, the researchers conducted tests looking for patients who showed clinically meaningful worsening over the course of infusion cycles — which would be expected if the effects of Ocrevus diminished between infusions.

Across the various symptom assessments, the researchers found that a handful of patients did experience worsening symptoms between infusions. However, for all the measures, there was also a similar number of patients whose symptoms eased between infusions — the opposite of what would be expected if the therapy was wearing off. On average, scores generally were stable or improved slightly between infusion cycles.

Further statistical analyses showed no clear clinical differences between patients who did or did not have worsening symptoms between infusions. Among patients with more than one cycle’s worth of data available, trends mostly were not consistent from cycle to cycle.

Younger patients with greater disability more likely to report ‘wearing off’ effect

The only trend with a persistent effect was a tendency for patients who reported wearing off to report more days missed from work toward the end of infusion cycles.

Collectively, these data “cast doubt on the existence of wearing off as a physiologic phenomenon defined by consistent worsening of symptoms toward the end of the infusion cycle and consistent improvement with reinfusion,” the researchers wrote.

“Our data show that symptom improvement and worsening occur independently of the time from the infusion and are, therefore, unlikely to be due to infusion,” they added.

Throughout the study, the researchers took explicit steps to avoid mentioning the idea of ‘wearing off’ so as not to bias patients’ expectations. Once the study was over, patients were sent a questionnaire that asked if they had ever experienced wearing off.

More than half (54.5%) of the respondents reported having ever experienced wearing off. Statistical analyses showed that these patients tended to be younger with more substantial disability.

The scientists speculated that these patients may be more acutely aware of variations in the severity of their symptoms. But they emphasized that further study is needed to better understand why symptom severity fluctuates over time for people with MS, noting that this is “a question that has not received sufficient attention to date.”

Researchers also noted that this study is limited by its relatively short duration and small size, highlighting a need for additional research to further verify the results.