Ocrelizumab (Ocrevus®) reduces increased cell percentages of TH40 cells in peripheral blood, which are biomarkers for chronic inflammation in multiple sclerosis (MS), a recent study published in the Journal of Neuroimmunology revealed.

The research team included patients diagnosed with clinically isolated syndrome (CIS), relapsing MS (RMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS) along with healthy controls who had no autoimmune disease, chronic illness, or infectious disease. Participants were recruited from various departments of the University of Colorado.

The researchers found that TH40 cells from patients treated with ocrelizumab produced significantly fewer inflammatory cytokines. This suggests that ocrelizumab acts by reducing TH40 cell numbers and function.


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Study results revealed that the peripheral blood in CIS accounts for a wide range of TH40 cell numbers equivalent to RMS. Moreover, at diagnosis, the SPMS and PPMS patients showed considerably elevated TH40 cell numbers, suggesting that SPMS and PPMS maintain chronic inflammatory conditions.

Furthermore, the presence of TH40 cells in the cerebral spinal fluid of RMS patients demonstrated the ability of this type of cell to break through the CNS.

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“The discovery that expanded percentages of TH40 cells occur in SPMS and remain elevated longitudinally suggests that the autoimmune inflammatory pathway does not diminish post-progression,” the authors noted. “Another conclusion is that systemic autoimmune inflammation plays an integral part in secondary progressive MS.”

“The discovery of elevated TH40 cells in PPMS also suggests that systemic autoimmune inflammatory pathways are present even in primary progressive disease. This observation is novel,” they added.

Ocrelizumab is a humanized monoclonal anti-CD20 antibody that causes the depletion of mature B cells. It mostly decreases the number of gadolinium-enhancing lesions on MRI scans of the brain and hence improves the Expanded Disability Status Score (EDSS). Moreover, compared to other disease-modulating therapies, it delays progression and slows the disease progression in SPMS and PPMS.

Approximately 50% of CIS cases are estimated to advance to RMS over 10 years. RMS accounts for approximately 80% of MS. Nearly 50% of the diagnosed RMS cases progress to SPMS in about 15 years, with approximately 90% converting after 25 years. PPMS is rarest and more neurodegenerative at onset and accounts for less than 5% of MS cases.

References

Curran C, Vaitaitis G, Waid D, et al. Ocrevus reduces TH40 cells, a biomarker of systemic inflammation, in relapsing multiple sclerosis (RMS) and in progressive multiple sclerosis (PMS). Journal of Neuroimmunology. Published online December 7, 2022. doi:10.1016/j.jneuroim.2022.578008