Most disability worsening on Ocrevus not tied to relapses: Study

Among multiple sclerosis (MS) patients treated with Ocrevus (ocrelizumab), most of the disability worsening they experience is not associated with any relapse activity, according to an analysis of real-world data.

“We present real-world data from our multiple sclerosis center underlining that in a typical population of relapsing MS treated with ocrelizumab most of the disability worsening occurred independently of relapses,” researchers wrote.

The study, “Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials,” was published in Scientific Reports.

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Ocrevus works by killing B-cells involved in MS-causing inflammatory attack

Ocrevus is an approved treatment for relapsing types of MS, and also for primary progressive disease. It’s administered via infusion every six months, and it works by killing B-cells, a type of immune cell involved in the inflammatory attack that causes MS.

Relapsing forms of MS are marked by relapses or flares where symptoms suddenly worsen, which are followed by periods of remission where symptoms ease.

Sometimes, symptoms that worsened during a relapse will persist even after the person achieves remission. This is called relapse-associated worsening, or RAW. It’s also possible for people with relapsing MS to experience worsening disability in the absence of any relapses, which is called progression independent of relapse activity, or PIRA.

In this study, scientists in Germany reviewed clinical data from MS patients at their center with the aim of better understanding the roles of RAW and PIRA in disability progression among those treated with Ocrevus.

The analysis included data on 97 patients treated from 2018 to 2022. When they started Ocrevus treatment, the patients were, on average, in their early 40s, with an average disease duration of slightly more than 10 years.

Over an average of more than two years of follow-up, 23 (23.7%) of the patients experienced confirmed worsening in disability — defined as a meaningful increase in Expanded Disability Status Scale score that persisted for at least three months.

Among these 23 patients, three experienced RAW. In the other 20 cases, disability worsening was due to PIRA.

The researchers noted that these findings are similar to what was reported in clinical trials that tested Ocrevus in people with relapsing MS. In those studies, about 80% to 90% of worsening disability was due to PIRA.

“This striking similarity between data from a real-world setting and from the results of a state-of-the-art Phase 3 randomized controlled trial … adds confidence into both: the trustworthiness of this real-world data set on the one hand, but also the validity of results obtained from tightly controlled and arguably artificial [clinical trials] for the real-world clinical setting,” the team wrote.

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Researchers look for risk factors of progression independent of relapse activity

The researchers then conducted statistical analyses looking for factors associated with the risk of PIRA. Results suggested that patients who had been living with MS for less time were more likely to experience PIRA while on Ocrevus. Congruently, patients who experienced PIRA also tended to have received fewer prior MS treatments.

One possible explanation for these data could be that Ocrevus is less effective when used early, but according to the researchers, that interpretation is “misguided.” It’s much more likely that this is due to indication bias, they wrote, meaning patients who were prescribed high-efficacy Ocrevus early on were also probably those who had more aggressive early disease.

The fact that the study was done on data from real-world clinical practice is a limitation of this analysis.

“Taken with the appropriate amount of precaution and considering the exploratory approach, however, we do believe that our data has value for this field of research,” the scientists wrote.

Ocrevus is sold by Roche, which was not involved in this study. A few of the study co-authors disclosed having previously received compensation from Roche and other pharma companies.