New drug aims to "switch off" rheumatoid arthritis
Published on 10 Apr 2010
UK scientists are hopeful of developing a completely new approach that may "switch off" rheumatoid arthritis (RA).
Following encouraging results from a pilot study in a handful of patients with RA, a team of researchers funded by medical research charity Arthritis Research UK and pharmaceutical company GlaxoSmithKline will set up a small phase I multi-centre trial of a targeted T-cell anti-CD3 monoclonal antibody therapy called otelixizumab, in the next four to six weeks.
Lead researcher Professor John Isaacs, Professor of Clinical Rheumatology at Newcastle University's Musculoskeletal Research Group, said that if the drug was shown to be effective and safe in subsequent Phase II and III trials, it could be available for patients with rheumatoid arthritis in eight to ten years. It is currently in Phase III trials for autoimmune type 1 diabetes mellitus.
Researchers hope that otelixizumab will be as effective in reducing symptoms as the current "gold standard" therapy for severe rheumatoid arthritis, anti-TNF therapy, but will have a more sustained effect from just a one-off one course of treatment.
"Everything we know about this drug suggests that it has the potential to be a powerful treatment, but safety is paramount, and this is what we aim to demonstrate in this study," he added.
Forty patients from around the UK who have failed to respond to conventional drug treatment will receive otelixizumab or placebo intravenously over a five day period as part of the trial.
"There is preliminary preclinical and clinical data to believe that doses lower than those used in the pilot study may have clinical benefit with a more favorable safety and tolerability profile. Patients in the current trial will receive a much lower dose than we used previously. The first group of ten patients will receive the lowest dose, and if this dose proves to be safe, then the dose will also increase slightly for the next ten, and so on," explained Professor Isaacs.
"We aim to etermine a dose which is safe but which also appears to improve symptoms. We anticipate that the dose we identify in this manner will subsequently be studied in larger Phase II and III studies, specifically designed to demonstrate a beneficial effect on symptoms."
In an important aspect of the study, researchers from Newcastle University and King's College London, will also be performing laboratory studies aimed at identifying and analysing potential biomarkers in the blood that might predict whether or not a patient will have a sustained response to the therapy.
Rheumatoid arthritis, which affects around 380,000 people in the UK, is caused when the body's immune system attacks itself, causing inflammation, pain and stiffness in the joints. Other internal organs can also be affected.
CD3 is a molecule found on the surface of T-cells (white blood cells that control the body's immune response), and is important in stimulating the T-cells into action. Otelixuzumab, an anti-CD3 monoclonal antibody, works in two ways by latching onto T-cells, potentially switching them off and increasing regulatory cells that control inflammation .
If found to be both safe and effective, otelixizumab could rival anti-TNF therapy, which has to be administered to patients on an ongoing basis. Anti-TNF therapy, also pioneered and developed by Arthritis Research UK scientists, has revolutionised treatment of the condition for the past decade, if otelixizumab could give the same longterm benefit with only a short course of treatment, it would offer a real advantage.
The charity is funding the study with an experimental medicine grant of more than £450,000, with a further £1.7m from GlaxoSmithKline.
Professor Alan Silman, medical director of Arthritis Research UK, said that although the research was at a very early stage, the potential prize - a new and highly effective one-off treatment for rheumatoid arthritis - was very great.