Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS

• Published in: Neurology : neuroimmunology & neuroinflammation Vol. 8; no. 2
• Main Authors: Fernández-Velasco, José I, Kuhle, Jens, Monreal, Enric, Meca-Lallana, Virginia, Meca-Lallana, José, Izquierdo, Guillermo, Gascón-Giménez, Francisco, Sainz de la Maza, Susana, Walo-Delgado, Paulette E, Maceski, Aleksandra, Rodríguez-Martín, Eulalia, Roldán, Ernesto, Villarrubia, Noelia, Saiz, Albert, Blanco, Yolanda, Sánchez, Pedro, Carreón-Guarnizo, Ester, Aladro, Yolanda, Brieva, Luis, Íñiguez, Cristina, González-Suárez, Inés, Rodríguez de Antonio, Luis A, Masjuan, Jaime, Costa-Frossard, Lucienne, Villar, Luisa M
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 04.03.2021
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Female; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Leukocytes - drug effects; Leukocytes - metabolism; Longitudinal Studies; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive - blood; Multiple Sclerosis, Chronic Progressive - drug therapy; Prospective Studies; Treatment Outcome
• ISSN: 2332-7812; 2332-7812
• DOI: 10.1212/NXI.0000000000000940

To analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS). In this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months' results. Values were corrected using the Bonferroni test. Ocrelizumab reduced the numbers of naive and memory B cells ( < 0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNFα) ( < 0.0001 in all cases). By contrast, the proportions of plasmablasts and B cells producing GM-CSF and TNFα increased significantly, suggesting the need for treatment continuation. We also observed a decrease in CD20 T-cell numbers ( < 0.0001) and percentages ( < 0.0001), and a clear remodeling of the T-cell compartment characterized by relative increases of the naive/effector ratios in CD4 ( = 0.002) and CD8 ( = 0.002) T cells and relative decreases of CD4 ( = 0.03) and CD8 ( = 0.004) T cells producing interferon-gamma. Total monocyte numbers increased ( = 0.002), but no changes were observed in those producing inflammatory cytokines. The immunologic variations were associated with a reduction of serum neurofilament light chain (sNfL) levels ( = 0.008). The reduction was observed in patients with Gd-enhanced lesions at baseline and in Gd- patients with baseline sNfL >10 pg/mL. In PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels.