#AANAM — Ocrevus Lowers Markers of Inflammation, Damage in Relapsing MS Patients, Phase 3 Trial Shows

#AANAM — Ocrevus Lowers Markers of Inflammation, Damage in Relapsing MS Patients, Phase 3 Trial Shows

Treatment with Ocrevus (ocrelizumab) decreases the levels of neurofilament light chain (NfL) and immune B-cells in the serum and central nervous system of patients with relapsing multiple sclerosis (MS), according to results from a Phase 3 trial.

The research, “Ocrelizumab treatment reduced levels of neurofilament light chain and numbers of B cells in the cerebrospinal fluid of patients with relapsing multiple sclerosis in the OBOE study,” was presented at the 2019 American Academy of Neurology (AAN) annual meeting, held May 4–10 in Philadelphia.

The data were presented by Amit Bar-Or, MD, chief of the MS division, department of neurology, at the Perelman School of Medicine at the University of Pennsylvania.

NfL levels in the serum and cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — as well as the number of lymphocytes in the CSF, have been increasingly proposed as biomarkers of nerve fiber (axonal) damage and inflammation, respectively, and subsequently of disability.

Researchers believe that the responses of these biomarkers to treatment with Ocrevus (marketed by Genentech) may improve understanding on both MS disease processes and the therapy’s mechanism of action.

To examine this, researchers conducted an early analysis in 100 patients with relapsing MS taking part in a trial called Ocrelizumab Biomarker Outcome Evaluation, or OBOE (NCT02688985), a CSF and blood biomarker study. This trial is still recruiting participants. More information on study locations and contacts can be found here.

In the OBOE trial, patients receive 600 mg infusions of Ocrevus every 24 weeks. CSF samples are collected by spinal tap prior to and at 12, 24 and 52 weeks of treatment. The study’s primary goal is the change in NfL levels and lymphocyte numbers in the CSF.

Results showed that pre-treatment CSF and serum levels of NfL significantly correlated with each other, and were associated with the number of both T1 gadolinium-enhancing lesions — areas of active inflammation — and new/enlarging T2 lesions — referring to the total amount of lesions, both old (non-active) and new — on brain magnetic resonance imaging (MRI).

Treatment with Ocrevus significantly reduced the number of T1 and T2 lesions. According to Bar-Or, there were “very few gadolinium-enhancing T1 or new/enlarging T2 lesions post-ocrelizumab” treatment, a result consistent with previous data from other clinical trials.

The treatment also lowered serum NfL (by 13.1%, 18.6%, and 30.8%), CSF NfL (by 24.5%, 40%, and 54.7%), and CSF B-cells (85.5%, 84.8%, and 94%) at weeks 12, 24, and 52, respectively.

Researchers saw “significant reductions in both CSF and serum levels of NfL, as early as 12 weeks post-ocrelizumab, and thereafter,” Bar-or said, suggesting a decrease in neuronal/axonal injury.

The number of immune T-cells in the CSF were decreased by approximately 60% across the same time points, but these reductions were only significant at week 12. “CSF T-cells were moderately reduced in many but not all patients,” the researchers wrote.

Overall, the lower levels of NfL and B-cells in relapsing MS patients suggest that treatment with Ocrevus “reduces ongoing axonal injury and compartmentalized CNS [central nervous system] inflammation,” the researchers wrote.

Of note, six of the study’s authors are affiliated with Genentech and one with Roche, which owns Genentech.

At the AAN meeting, Multiple Sclerosis News Today had the opportunity to interview Hideki Garren, MD, PhD, global head of MS and neuroimmunology at Genentech.

“We see a rapid decline both in blood and CSF NfL. The reason that’s important is that because disability progression can take a long time to measure clinically, this is potentially a marker that can be used to measure disability progression earlier because it rapidly goes down,” Garren said about the data presented by Bar-Or.

He also highlighted the fact that the rapid decline seen in NfL levels in patients receiving Ocrevus is not seen in control groups.

Using NfL levels as a routine biomarker in clinical practice, Garren said, “is potentially possible, especially with serum NfL levels. Up until now, the majority of research has been on CSF, which is not practical to follow up on patients long term, but with the advent of serum NfL … that really seems to be potentially practical for routine use. It certainly needs to be validated.”


  1. Charles Dick says:

    From my own personal experience as a patient, I think that Ocrevus is an amazingly good drug. To figure out the mysterious mechanism of action, I think we need to keep in mind that CD20 is not only expressed on B cells, but also on some T cells. The question is exactly which subsets of T cells express CD20. I would not be surprised to find that Th17 cells are among those that turn out to be CD20+. If that is actually the case, then perhaps a bimodal antibody simultaneously targeting CD20 and CD3 might be worth investigating.

  2. Why are all these phase 3 trials coming out now? How bout horrible migraines, skin blister, low blood pressure, and hair loss? I can get anti-inflammation drugs at CVS. I am tired of all these new chemotherapy drugs being used for auto-immune disorders. Maybe we should start addressing parasitic infections as root causes of our immune systems attacking our glucose covered nerve cells and brains. Ask your neurologist to talk about lyme disease and watch the type of response you get.

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