MS drug ocrelizumab dampens vaccine response

Two new unpublished studies took a closer look at the effects of ocrelizumab in patients with multiple sclerosis (MS). These studies were presented by first author Amit Bar-Or, MD, chief of the Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, at the American Academy of Neurology (AAN) Annual Meeting 2018 hosted in Los Angeles, CA, between April 21 and 28.

“Research like this allows us to learn more both about the mechanisms underlying MS activity and injury, as well as the biology of MS treatments, which in turn will help us better individualize treatments for specific patients,” said Dr. Bar-Or.

The FDA approved ocrelizumab in March 2017 as the first treatment for both relapsing and primary progressive MS. This drug targets and destroys cells with surface CD20, including many types of B cells. Although MS has been considered a T-cell–mediated autoimmune disorder, Dr. Bar-Or and colleagues previously discovered that ocrelizumab decreases the ability of B cells to stimulate not only T cells, but also other B cells and myeloid cells involved in MS flare-ups.

In the first study, Dr. Bar-Or and colleagues found that 12 to 24 weeks of ocrelizumab treatment decreased the number of biomarkers of neuronal inflammation and injury—including B cells, T cells, and neurofilament light chain. On the basis of these findings, Dr. Bar-Or suggested that interactions between B cells and T cells in the brain and spinal cord could contribute to MS nerve damage. This study is ongoing, with final results expected in early 2019.

In the second study, Dr. Bar-Or and colleagues examined how effective different immunizations were in patients treated with ocrelizumab versus those not treated with the drug. They looked at patients’ vaccine responses to tetanus, seasonal flu, and pneumococcus, as well as a novel antigen called keyhole limpet hemocyanin neoantigen that patients were likely never exposed to before.

Although patients receiving ocrelizumab still mounted an immune response to vaccination, these vaccine responses were lower in those receiving the drug. For instance, about 24% of patients taking ocrelizumab showed a positive response to the tetanus vaccine after 8 weeks compared with about 55% of subjects who were not taking the drug.  

“This study shows that while people with MS treated with ocrelizumab can still mount vaccine responses, it’s not nearly as strong as prior to treatment,” Dr. Bar-Or said. “While antibody responses were reduced in the ocrelizumab treated patients, they still responded to a certain level. This is valuable information in terms of seasonal vaccines such as the flu—it appears safe for patients taking ocrelizumab to get vaccinated and vaccination is likely to provide them with at least some protection from such infections.”

The researchers suggested that patients should receive vaccinations no less than 6 weeks prior to starting ocrelizumab, in line with the current prescribing information.

These studies were sponsored by Genentech, developer of ocrelizumab.