Findings may help optimize therapy for patients considering Ocrevus

The way Ocrevus (ocrelizumab) affects immune cell profiles of people with multiple sclerosis (MS) varies depending on what treatments they were on previously, a new study shows.

Understanding these differences could help to optimize treatment approaches for MS patients considering Ocrevus, scientists say.

The study, “Previous disease-modifying treatments influence T lymphocyte kinetics in people with multiple sclerosis switching to ocrelizumab,” was published in the Journal of Neuroimmunology.

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Ocrevus works by destroying B-cells, reducing inflammatory activity

Ocrevus is widely approved to treat relapsing forms of MS, and it was the first therapy approved for primary progressive disease. The medication works mainly by destroying B-cells, a type of inflammatory immune cell. Ocrevus treatment is also believed to reduce the inflammatory activity of other immune cells, such as T-cells.

A report published in 2021 suggested that the effectiveness of Ocrevus in MS might vary depending on a patient’s history of other treatments. Specifically, the report indicated that patients who switched to Ocrevus from Gilenya (fingolimod) were more likely to experience a disease relapse compared with those who switched from Tysabri (natalizumab).

To explore these potential interactions, scientists in Italy assessed how Ocrevus treatment affected lymphocytes — the group of immune cells that includes B-cells and T-cells — in 147 people with MS who started on the therapy at four Italian MS centers between January 2018 and April 2021.

Among the patients, 56 had not received any MS treatment before Ocrevus, while 54 switched to Ocrevus from Gilenya and the other 37 switched from Tysabri.

Overall, our results suggest that the previous [treatments] influence the kinetics of T lymphocyte subsets of patients treated with [Ocrevus].

There were some notable demographic and clinical differences among the groups; for example, patients who were new to treatment had generally lived with MS for less time and more frequently had primary progressive disease.

In turn, patients switching from Gilenya had significantly more disability when they started Ocrevus than the other two groups. There were also differences among the groups in lymphocyte counts prior to starting Ocrevus.

Using statistical models to account for these differences, the researchers compared how lymphocyte populations shifted among these patient groups after six months on Ocrevus.

The change in B-cell levels was not significantly different between the three groups after statistical adjustments. Levels of natural killer cells, another type of lymphocyte, also did not differ substantially between the groups. However, there were some notable differences in T-cell profiles.

“Conversely to what was observed for B-cell kinetics, the difference in T-cell kinetics among the three groups remained consistent even after the adjustment for baseline lymphocyte count,” the researchers wrote.

In patients who had not been on prior treatment or who had been on Tysabri previously, levels of CD8 T-cells — a type of inflammatory T-cell with the capability to kill other cells — decreased after six months of Ocrevus. However, for patients who had been on Gilenya previously, levels of CD8 T-cells increased after Ocrevus treatment.

In all three patient groups, levels of CD4 T-cells (which are mainly responsible for secreting signaling molecules to coordinate immune activity) decreased after six months of Ocrevus — however, the magnitude of the decrease was markedly lower for patients who had been on Gilenya previously, but higher for patients on Tysabri previously.

The ratio of CD4 to CD8 T-cells decreased in patients who had been on prior Gilenya treatment, but this ratio increased for patients who had been on Tysabri or who had not been on prior treatment.

“Overall, our results suggest that the previous [treatments] influence the kinetics of T lymphocyte subsets of patients treated with” Ocrevus, the researchers concluded.

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22 patients experienced inflammatory disease activity

Over the six months studied, 22 of the patients experienced inflammatory disease activity (defined as a relapse and/or new activity on MRI scans). Among them, six were new to treatment, nine had previously been on Gilenya, and seven had been on Tysabri.

There were no differences in inflammatory activity based on prior treatment, though the researchers cautioned that this study is likely too small to detect a meaningful difference.

Whether the detected differences in T-cell profiles translates to differences in clinical efficacy “remains an open question,” the researchers wrote, adding that better understanding could help guide treatment.

“Further longitudinal studies in larger cohorts of people with MS may help optimize the therapeutic switch,” the scientists wrote.

Patients who experienced inflammatory activity tended to have lower levels of CD8 T-cells when they started on Ocrevus.

This is likely attributable to the prior treatments, because both Gilenya and Tysabri work by altering the movement of T-cells and other lymphocytes. As a consequence, inflammatory cells become “trapped,” the researchers wrote. When patients switched to Ocrevus, these cells may have been able to move again, allowing them to get into the brain and cause new inflammatory activity.

“The association between a lower CD8 T-cell count at baseline and the higher likelihood of experiencing early disease activity shown in our population may be explained by this phenomenon,” the team wrote.