ADAs to alemtuzumab
Research type
Research Study
Full title
Impact of anti-drug antibodies to alemtuzumab in multiple sclerosis
IRAS ID
304993
Contact name
Sharmilee Gnanapavan
Contact email
Sponsor organisation
Barts Health NHS Trust
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary:
One of the treatments for Multiple Sclerosis (MS) called alemtuzumab has been shown to be good at reducing the flares in MS.
Sometimes, our own bodies react differently to drugs than expected, making them less effective and predictable. This does not happen that frequently, but it is important that we understand what is happening and why by learning more about the reasons. In some circumstances, the body may make something called anti-drug antibodies (ADA’s), and this study is investigating how and when this may happen.
Research Findings:
Alemtuzumab is a drug used to treat relapsing-remitting multiple sclerosis (MS), a condition in which the immune system damages the brain and spinal cord. It works by reducing certain immune cells involved in this damage. However, the immune system can also produce antibodies that recognise the drug itself. These are called anti-drug antibodies. Understanding when they appear and how long they remain may help researchers assess whether antibody testing could support future treatment decisions.
This study investigated changes in antibodies against alemtuzumab over two years and measured the amount of the drug remaining in the blood. Seventeen people receiving alemtuzumab at Barts Health NHS Trust joined the study. Fifteen completed the two-year follow-up and were included in the analysis; two withdrew or were lost to follow-up. Blood samples were collected before treatment, during treatment infusions and at several visits after the first and second treatment courses, which were given approximately one year apart.
The laboratory testing approach was adapted during the study after difficulties with the original assay development. A commercially available laboratory test was used to measure antibodies against alemtuzumab.
Antibody responses varied considerably between participants. Antibodies were detected within the first month after the first treatment course, with levels generally highest around two to three months. Levels subsequently decreased before the second course. Following the second course, antibody responses were generally higher and remained elevated for longer. Some samples contained antibody levels above the range that the test could measure accurately, even after dilution. These samples showed strong antibody responses, but their exact concentrations could not be determined reliably.
Alemtuzumab levels in the blood were highest during treatment infusions and decreased afterwards. By two months after the first course, levels were below the test’s measurement limit in most participants. A similar pattern was observed after the second course. Antibody levels generally peaked later than drug levels. This difference in timing describes how the two measurements changed; it does not establish whether the antibodies affected treatment effectiveness.
The study contributes to understanding how antibodies against alemtuzumab develop after repeated treatment.
The patient study was small, some samples were unavailable, and very high antibody levels could not always be measured precisely. The results presented here do not establish whether these antibodies increased infusion reactions, reduced the drug’s effects on immune cells or changed MS outcomes. Further assessment of these relationships is needed to determine whether antibody testing could help guide additional treatment courses.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
22/NE/0029
Date of REC Opinion
10 Mar 2022
REC opinion
Further Information Favourable Opinion