#AAN2018 — Ocrevus Lowers Immune Response to Vaccines in Relapsing MS, Phase 3 Trial Shows

#AAN2018 — Ocrevus Lowers Immune Response to Vaccines in Relapsing MS, Phase 3 Trial Shows
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Treatment with Ocrevus (ocrelizumab) is linked to a reduced immune response to vaccinations in patients with relapsing multiple sclerosis (MS), according to a Phase 3 trial.

These results were recently presented at the 2018 American Academy of Neurology (AAN) Annual Meeting in Los Angeles in a presentation titled, “Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis.

Genentech’s Ocrevus is an approved MS therapy that targets the CD20 protein located on the surface of B-cells, targeting the cells for destruction. B-cells are immune system cells involved, for example, in the production of antibodies necessary to fight off infection.

At the AAN meeting, researchers reported that in MS patients, treatment with Ocrevus decreased the ability of B-cells to activate other immune cells, improving the rate of MS attacks. Penn Medicine neurologist Amit Bar-Or, MD, presented these findings, which showed that interactions between different classes of immune cells, such as B- and T-cells, promote MS attacks.

Vaccination against infections is an important part of the management of patients with MS. So, in a second study (NCT02545868), researchers investigated the impact treatment with Ocrevus has on patient response to vaccines.

They recruited 102 patients with relapsing MS and randomized them in two groups. In group A, 68 people received a single dose of 600 mg Ocrevus (administered into the blood); in group B, 34 patients received no disease-modifying therapy or interferon-beta.

All patients were then administered vaccines for tetanus, seasonal flu, and pneumococcus. Patients in group A received the vaccines 12 weeks after they were treated with Ocrevus, while group B patients received the vaccines on day one.

Researchers also tested patients’ response to a novel protein (an antigen) never “seen” by their immune system, called keyhole limpet hemocyanin (KLH) neoantigen.

The vaccinations led to an immune system response in all patients, but the level of response in patients treated with Ocrevus was lower. A positive response to the tetanus vaccine at eight weeks after treatment was 23.9% in group A (Ocrevus) compared with 54.5% in group B (no treatment); the response to pneumococcus vaccination was 71.6% in group A and 100% in group B.

After four weeks of treatment, the levels of antibodies against the different strains of the flu virus were lower in Ocrevus-treated patients than in the control group, ranging from 55.6% to 80.0% in the Ocrevus group compared with 75.0% to 97.0% in the controls.

The immune response to the neoantigen KLH was also decreased in the Ocrevus group.

“This study shows that while people with MS treated with ocrelizumab [Ocrevus] can still mount vaccine responses, it’s not nearly as strong as prior to treatment,” Bar-Or said in a press release.

“While antibody responses were reduced in the ocrelizumab treated patients, they still responded to a certain level,” he said. “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.”

These findings correlate with standard guidelines that advise patients to undergo vaccinations six weeks before they start treatment with Ocrevus.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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