An interim analysis showed no reduction in T-cell counts and their subsets as a consequence of B-cell depletion in the first year of treatment with ocrelizumab.
Findings from a 12-month interim analysis of the phase 3 ENSEMBLE (NCT03085810) trial showed that ocrelizumab (Ocrevus; Genentech) induced significant depletion of all B-cell subsets in patients with early relapsing-remitting multiple sclerosis (RRMS).1
After 24 and 48 weeks, results showed a significant (P <.0001), stable and virtually complete depletion of all B-cell subsets, including naive, memory, transitional and regulatory B-cells, in treated patients. After 24 weeks, a transient increase (P <.01) in T-cell subset (CD4/CD8 naive, memory, Th1, Th2, Th17, Tregs) counts was observed that returned back to baseline levels after 48 weeks.
Senior author Luisa H. Klotz, MD, professor of neurology, Institute of Translational Neurology, University Hospital of Münster, Westfälische-Wilhelms-University Münster, Münster, Germany and colleagues presented the findings at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts. In this analysis, investigators explored the immunological effects associated with ocrelizumab treatment in the blood of early, previously treatment-naive patients with MS by multiparameter flow cytometry.
Patients, aged 20-56 years old with a RRMS disease duration of less than 3 years received ocrelizumab 600 mg every 24 weeks. A comprehensive characterization of the quantitative changes of circulating T-cells, B-cells, NK-cells, myeloid cells, dendritic cells and their subsets and function were performed in 65 patients, measured relative to baseline (pre-infusion) at 24 and 48 weeks after first ocrelizumab infusion. Using Kruskal-Wallis test, median cell counts (cells/μL) were evaluated followed by Dunn’s test with Bonferroni correction.
Notably, an increase in CD69 expression levels (CD4/CD8 T-cells) and HLA-DR+ CD8 T-cell counts were observed at week 24 compared with baseline, which decreased until 48 weeks. Additionally, there was no reduction observed of CD4 and CD8 T-cells and their subsets up to 48 weeks. Also, the changes induced on other lymphocyte subsets remained transient in the first year of treatment.
"Dysregulation in immune regulatory networks is one hallmark of MS pathophysiology, particularly in early RRMS. Considering the efficacy of B-cell-depleting therapies, it is of particular interest to explore the impact of ocrelizumab on peripheral immune signatures in a previously treatment-naive cohort," Klotz et al wrote.1
Data presented at the 2020 Consortium of Multiple Sclerosis Centers (CMSC) Virtual Annual Meeting on the ENSEMBLE PLUS study of ocrelizumab revealed that the frequency and severity of infusion-related reactions (IRR) are comparable between the conventional, approved 3.5-hour infusion time versus shorter infusion times nearing 2 hours in patients with RRMS.2 The data showed that 67 (23.1%) of the 291 patients and 71 (24.6%) of the 289 patients randomized to conventional and shorter infusion groups, respectively, had IRRs.
For context, the FDA approved a shorter 2-hour infusion time of ocrelizumab, supported by ENSEMBLE PLUS data, for dosed twice-yearly for patients with relapsing or primary progressive MS who have not experienced any prior serious IRRS in December 2020.3 In April 2020, the agency accepted the supplemental biologics license application (sBLA) for the shorter infusion. In 2017, ocrelizumab was approved as the first of its kind treatment of primary progressive MS.