Without treatment, multiple sclerosis (MS) is commonly a disabling disease. Alemtuzumab (Lemtrada®) is a proven and approved therapy for MS that is highly effective but is associated with a 30-40% risk of developing other autoimmune diseases after treatment has been administered.
Alemtuzumab is an antibody therapy that works in MS by temporarily removing circulating immune cells. Following treatment, one type of immune cell, called B cells, are restored in the blood earlier than other immune cells. Normally, B cells are controlled by another immune cell called T cells. When B cells return after alemtuzumab treatment without the controlling effect of T cells, this may contribute to the risk of developing another autoimmune disease (autoimmunity).
It has been suggested that another antibody therapy which targets B cells, called rituximab, might help prevent autoimmunity after alemtuzumab treatment.
The aim of the RAMBLE clinical trial is to see if treatment with rituximab reduces the risk of autoimmunity following alemtuzumab treatment in MS. This would make treatment with alemtuzumab more appealing to people with MS and their MS care team.
Ms Jimenez-Sanchez’ PhD project took a detailed look at immune responses in ten of the trial participants. The aim was to better understand how alemtuzumab works, how other autoimmune diseases develop after this treatment, and how rituximab might help correct this.
As of March 2025, Ms Jimenez Sanchez has recruited ten participants for her PhD project within the RAMBLE study. Blood samples from participants have been collected for genetic and viral load studies, with most also taking part in cytokine and immune cell analyses. Preliminary findings show that alemtuzumab leads to rapid B cell repopulation, while rituximab results in a slower return of B cells, supporting its potential role in reducing treatment-related autoimmunity.
The detailed analysis of the immune system has been completed in four participants, and follow-up will continue over the next three years to track longer-term immune responses and the development of secondary autoimmunity. Despite some participants withdrawing from the project, valuable data has been obtained through partial participation in key blood sample collection.
In parallel, Ms Jimenez Sanchez completed and published a systematic review titled “The role of alemtuzumab in the development of secondary autoimmunity in multiple sclerosis” in the Journal of Neuroinflammation, providing important context for the ongoing clinical study.
This project provides new insights into how the immune system responds to alemtuzumab treatment and why some people develop autoimmune side effects.
After treatment with alemtuzumab, some T cells were reduced. These were older and more active T cells that can sometimes mistakenly attack the body. Reducing these may help explain both how alemtuzumab works and its impact on the immune system.
There were also fewer new (naïve) T cells being produced, suggesting the body is making fewer fresh immune cells. As a result, older immune cells that are more prone to autoimmunity can grow instead. This could help explain why some people develop new autoimmune conditions after treatment.
Ms Jimenez-Sanchez also measured immune signalling molecules in the blood, but there were no major changes with either treatment. This suggests the treatments mainly affect immune cells themselves, rather than the signals they produce.
In people who received rituximab, new B cells returned more slowly, and older memory B cells remained lower after almost one year. This suggests that combining alemtuzumab and rituximab may help new B cells return in a more balanced way, while reducing those linked to autoimmune side effects.
Together, these findings provide important insight into why autoimmune side effects occur after alemtuzumab and how they might be prevented. They support further investigation of combined treatment as a potential approach to maintain the benefits of alemtuzumab while reducing the risk of secondary autoimmunity.
These findings have been included in a manuscript submitted for publication.
While Ms Jimenez-Sanchez’ project is now complete, the broader team are continuing to work on the RAMBLE trial to determine the clinical outcome of this intervention, and next steps.
Jimenez Sanchez, A., & Broadley, S. (2024). The role of alemtuzumab in the development of secondary autoimmunity: A systematic review. Journal of Neuroinflammation, 21(1), Article 70. https://doi.org/10.1186/s12974-024-03263-9
Updated 31 March 2026
Donald and Joan Wilson Foundation
$105,000
2023
3 years
Past project
