B Cell Suppression Not Correlated With Therapeutic Response in Ocrelizumab-Treated Patients

Antonio Scalfari, MD, PhD

Findings from a single-center study of patients with relapsing-remitting multiple sclerosis (RRMS) indicated that therapeutic response with ocrelizumab (Ocrevus; Genentech) was not correlated with B cell depletion levels. Despite this, patients with more effective B cell depletion had larger percentages in Expanded Disability Status Scale (EDSS) progression and progression independent of relapse activity (PIRA).¹

The data were presented at MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, in Milan, Italy. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved by the FDA in March 2017 after pivotal trials showed dramatic reductions in inflammatory disease activity in relapsing MS as well as lessening of disability progression in primary progressive MS. Compared with patients with B cells that were not suppressed (BN, n = 48), those with B cell suppression (BS, n = 379) had a lower proportion of relapses (14.8% vs 20.8%; P = .4) and new MRI activity (4% vs 8.3%; P = .01); however, these differences were not significant.

Senior investigator Antonio Scalfari, MD, PhD, a neurologist at Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom, and colleagues retrospectively analyzed 427 patients with RRMS, mostly female (62.6%), over a 30-month period. Presented at MSMilan 2023, the 9th Joint ECTRIMS-ACTRIMS Meeting, held October 11-13, in Milan, Italy, patients received a mean of 5.1 ocrelizumab infusions, with B cell suppression defined by an absolute count of less than 50 B cells at last assessment.

At the last infusion, the mean B cell count changed from 271.8 at baseline to 16, while the mean EDSS score changed slightly from 3.9 to 4. Using Kaplan-Meier analysis, patients with BS took longer time to experience relapse (61.2 vs 45.7 months; P = .4), new MRI activity (68.5 vs 44.9 months; P = .1), EDSS improvement (61.2 vs 45.7 months; P = .4), EDSS progression (60.1 vs 45.6 months; P = .08) and PIRA (61.2 vs 45.6 months; P = .1).

READ MORE: Anti-CD20 Therapies Shown to be Effective After Switch From Natalizumab

Although the 2 groups had similar age of onset (33 vs 33; P = .8), those with BS had shorter disease duration (10.8 vs 11.9 years; P = .03) and lower EDSS at baseline (3.8 vs 4.7; P = .01) and at last assessment (3.9 vs 4.7; P = .04). Additionally, this group received more ocrelizumab infusions (5.2 vs 4.5; P <.001) over the 30-week period. As for the reasons why B cell suppression may have led to larger EDSS percentages and PIRA, the investigators concluded that, “systemic B cell measures have a role in inflammatory activity but might be not involved in the pathogenesis of clinical progression.”

Over the years, the success of selective B cell depletion in patients with RRMS has highlighted their essential role in both the inflammatory and neurodegenerative components of the disease process. On behalf of an expert panel of the 27th ECF Annual Meeting, a group of experts published research in 2020 on the role of B cells in MS and related disorders, writing that peripheral B cells of these patients “exhibit aberrant proinflammatory cytokine responses.” This includes exaggerated lymphotoxin-a, tumor necrosis factor-alpha, interleukin-6, and granulocyte macrophage-colony stimulating factor secretion.

"B-cell depletion results in significantly diminished pro-inflammatory responses of CD4+ and CD8+ T cells as well as myeloid cells," senior author Stephen L. Hauser, MD, et al wrote. "It is noteworthy that a small proportion of circulating T cells express CD20 and these are also depleted with anti-CD20 therapy; though, since anti-CD19 therapy also seemed effective in MS, the robust effects of anti-CD20 in MS are not likely to be exclusively mediated by removal of CD20-expressing T cells."

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REFERENCES
1. Polidoro F, Zito A, Singh-Curry V, et al. The correlation between B cells depletion and the therapeutic response, among MS patients treated with ocrelizumab. Presented at: MSMilan2023, October 11-13, Milan, Italy. Abstract 329
2. Comi G, Bar-Or A, Lassmann H, et al. The role of B cells in multiple sclerosis and related disorders. Ann Neurol. 2021;89(1):13-23. doi:10.1002/ana.25927.