Switch to Ocrelizumab Shows Safety in Patients With Relapsing MS

Patients with relapsing multiple sclerosis (RMS) who had a suboptimal response to previous disease-modifying therapies (DMTs) could have an alternate source of treatment, as switching to ocrelizumab (Ocrevus; Genentech) was found to be safe and led to durable control of the disease, according to a study published in the European Journal of Neurology.¹

Ocrelizumab is a humanized monoclonal anti-CD20 antibody and was approved for RMS in 2017 due to demonstrating superior efficacy compared with interferon beta-1a (Rebif; Pfizer).² The medication was primarily tested in those who were treatment naive, which could limit generalizability to those who had previously been treated. This phase 3 extension study, LIBERTO (NCT03599245), aimed to assess the long-term effectiveness and safety of ocrelizumab in patients who had been enrolled in the CASTING (NCT02861014) and ENSEMBLE (NCT03085810) trials, with data collected over 4 years of the CASTING study and rolled over into the LIBERTO study.¹

The LIBERTO study was a 2-year, multicenter, single-arm study that enrolled patients with RMS starting on July 12, 2018. All included participants had completed the CASTING study. Individuals were excluded if they had hypersensitivity to ocrelizumab treatment, had concomitant medications, had an intention to become pregnant, were in an unresolved severe immunocompromising state, or had evidence of any adverse events.

Patients received ocrelizumab every 24 weeks through week 168. The Expanded Disability Status Scale (EDSS) score was used to assess effectiveness every 24 weeks through week 192 of LIBERTO as well as baseline. MRI data were also collected at baseline. The primary end point was the proportion of patients with no evidence of disease activity (NEDA) over a 4-year treatment period. The proportion of patients with a 24-week and 48-week confirmed disability progression (CDP), patients with confirmed disability improvement annualized relapse rate, and change in cognitive performance were secondary end points.

There were 299 patients who rolled over to the LIBERTO study and completed the study, of which 62.9% were women. Most patients had not experienced clinical or radiological activity after 4 years of treatment, with most not having experienced 24-week CDP (79.7%; 95% CI, 75.3%-83.4%). Most participants also had no relapses (86.7%; 95% CI, 83.0%-89.4%) and no MRI activity after rebaselining at week 8 (89.9%; 95% CI, 86.6%-92.4%). NEDA was found in 65.6% of patients over the 4-year period when 24-week CDP was a disability component. NEDA was achieved by 84.8% or more patients each year.

A total of 24.0% of patients who had an EDSS score of 2.0 saw improvement in disability status 24 weeks after the first event was recorded. Through 48 weeks, this decreased to 20.7%. A total of 86.7% of the intention-to-treat population remained relapse free through 4 years. Information processing speed remained stable for most of the patients (61.4%). Switching to ocrelizumab also resulted in fewer missed work days, less impairment at work, less impairment in nonwork activities, and less work productivity loss. Adverse events were experienced by 92.9% of the patients, and a severe adverse event was experienced by 9.3%. Infusion-related reactions and infections were the most common adverse events. Mild or moderate adverse events were most common.

There were some limitations to the study. No conclusion on treatment effects could be drawn due to the single-arm design. The population had a short disease duration and may not be generalizable to other patients. Survivorship and attrition bias were possible due to the rollover design of the study. The outcomes in patients who switched from other high-efficacy DMTs could not be assessed.

“This study suggests that, for patients with early RMS and suboptimal response to previous DMTs, switching to ocrelizumab is safe and results in significant and durable control of disease severity,” the authors concluded.

References

1. Vermersch P, Benedict RHB, Van Wijmeersch B, et al. Efficacy and safety of patients with relapsing multiple sclerosis switching to ocrelizumab due to suboptimal treatment response: results of the 4-year CASTING-LIBERTO trial. Eur J Neurol. 2026;33(6):e70628. doi:10.1111/ene.70628
2. FDA approves Genentech’s OCREVUS (ocrelizumab) for relapsing and primary progressive forms of multiple sclerosis. News release. Genentech. March 28, 2017. Accessed June 22, 2026. https://www.gene.com/media/press-releases/14657/2017-03-28/fda-approves-genentechs-ocrevus-ocrelizu