# Safety and efficacy of B-cell therapy in older people with multiple sclerosis

**Authors:** Turlough Montague, Yuuki Kang, Karen Thomas, Nicole Burke Simpson, Celia Miller, Sophie Chatterton, Ariadna Fontes Villalba, John Parratt

PMC · DOI: 10.3389/fimmu.2025.1699550 · 2026-01-28

## TL;DR

This study examines how well and safely B-cell therapy works in older adults with multiple sclerosis, finding it effective but with some risks.

## Contribution

The study provides evidence on the safety and efficacy of B-cell therapy in older MS patients, a group often underrepresented in clinical trials.

## Key findings

- 77.9% of patients achieved NEDA-3, indicating no evidence of disease activity.
- Immunoglobulin levels (IgM, IgA, and IgG) significantly declined during treatment.
- Adverse events occurred in 50.7% of patients, leading to discontinuation in 10.7%.

## Abstract

The MS population is aging, with nearly one-third now over 55 years. This group is underrepresented in trials and less often prescribed high-efficacy therapy (HET). Although phase III studies of ocrelizumab and ofatumumab confirmed efficacy in younger patients, the risk–benefit profile in older people with MS (opwMS) is less established given reduced relapse activity and higher risks of infection and malignancy.

We retrospectively reviewed opwMS (≥ 55 years) treated with ocrelizumab or ofatumumab at a tertiary centre, evaluating clinical outcomes, MRI activity, and adverse events.

Among 140 patients (67% (94) female, mean age 63), median disease duration was 16 years and B-cell therapy duration 44 months; 91% (127) had prior DMT exposure. During treatment, 77.9% (109) achieved NEDA-3, EDSS remained stable (3.38 to 3.44, p=0.67), and PIRA was reduced by 15%. Adverse events occurred in 50.7% (71%), leading to discontinuation in 10.7% (15). Immunoglobulin levels fell significantly (IgM, IgA, and IgG). In 47 patients ≥ 65 years, adverse event rates were similar, 69.6% (33) achieved NEDA-3, but EDSS increased (p=0.034).

Over 44 months, B-cell therapy in opwMS (mean age 63) showed safety and efficacy comparable with younger cohorts, although immunoglobulin decline and discontinuation due to adverse effects highlight the need for monitoring.

## Linked entities

- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}
- **Diseases:** MS (MESH:D009103), infection (MESH:D007239), malignancy (MESH:D009369)
- **Chemicals:** DMT (MESH:D004130), ofatumumab (MESH:C527517), ocrelizumab (MESH:C533411)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12892219/full.md

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Source: https://tomesphere.com/paper/PMC12892219