Graves-PCD
Research type
Research Study
Full title
Randomised controlled trial of plasma cell depletion for severe Graves’ disease
IRAS ID
1003652
Contact name
Simon Pearce
Contact email
Sponsor organisation
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Eudract number
2020-005635-78
Research summary
Research Summary:
Graves' disease gives symptoms such as heart palpitations, heat intolerance, unintended weight loss, enlarged thyroid, red and swollen eyelids, protuberant eyeballs and double vision. Patients with severe Graves' disease frequently have disabling eye disease and occasionally loss of vision. Treatment with antithyroid drugs lead to remission in only around 50% of people, which falls to around 20% for people with severe Graves' disease, and does not improve the eye problems. Patients with severe Graves' disease often have their thyroid gland removed surgically, followed by several eye operations to correct the visual function and appearance of the eyes. These are expensive operations with low overall patient satisfaction. Better treatments are needed.
The antibodies (known as TRAb) that drive the thyroid and eye symptoms are produced by a type of white blood cell called a plasma cell, whose sole purpose is to make large quantities of antibodies. This Medical Research Council funded trial will find out whether a new treatment called daratumumab that has been developed to treat plasma cell cancer, could also be used to target the benign plasma cells in patients with severe Graves' disease. By removing plasma cells in Graves' disease, we would expect a reduction in the disease-causing TRAb antibody concentration and a rapid improvement in the thyroid overactivity and eye symptoms.
This study will perform a 2-stage randomised trial of daratumumab in 30 patients with severe Graves' disease. Because daratumumab has not been used in Graves' disease before, the first part of our study will administer 4 different doses or a placebo to small groups of participants to see which of the doses works best. Then we will use one or 2 of the best daratumumab doses or a placebo to treat a larger groups of patients. The daratumumab is given twice by intravenous infusion to each participant, and participants will be followed up in a further 4 clinic appointments across 6 months.
Lay Summary of Results:
Why was the trial needed?
Graves’ disease is an autoimmune condition that affects the thyroid. It mostly affects women. Patients with severe Graves’ disease often don’t get better just by taking medication and can need treatments like radioactive iodine or surgery to remove the thyroid gland. While these treatments work, they aren't suitable for everyone, and some people don't see significant improvements in their quality of life. This trial aimed to find a better treatment.What did we want to find out?
We wanted to see if a medicine called daratumumab, which is safely used to treat patients with other health conditions, could help people with severe Graves' disease. We also wanted to find out what would be the best dose to use.Who took part in the trial and what happened?
30 patients including 22 women took part in this trial at Newcastle Hospitals between October 2021 and March 2024.
In the first part of the trial, 15 people got either: one of several different doses of the medicine or a dummy treatment (placebo) through a drip into their arm. Each person received two treatments with the medicine. We then checked the results and selected the two most effective doses of medicine to use. In the second part of the trial, another 15 people were treated with either the selected doses of the medicine or the dummy treatment.What were the results?
• The medicine was safe, with no unexpected problems.
• We checked if the medicine affected TRAb levels (a thyroid antibody that causes the disease) by taking a blood test after 12 weeks.
• There were three groups: no treatment (placebo), low dose, and high dose.
What were the results? (cont.)
• The high doses of medicine worked better (had more effect on TRAb levels) than low doses or no treatment.
• The medicine might not help people with the most severe forms of the disease.
• The medicine didn’t change other things we looked at, like thyroid size, eye problems, symptoms of hyperthyroidism or thyroid hormones.
• Patients might need more than two treatments for the medicine to be a cure for Graves' disease.What’s next?
We want to test the medicine in a bigger trial to see if more than two repeated doses can help treat the disease. However, daratumumab costs a lot of money, so we might need to find a different, cheaper medicine that works in a similar way.Who ran and funded the trial?
The Graves-PCD trial was funded by the UKRI Medical Research Council (MR/V005898/1). It was led by Prof Simon Pearce in collaboration with Newcastle Clinical Trials Unit and the Biostatistics Research Group, Newcastle University, on behalf of the Newcastle upon Tyne Hospitals NHS Foundation Trust (trial Sponsor).Where can I find out more?
Further information about the trial and a summary of results will be available at www.isrctn.com/ISRCTN81162400Thank you very much to all of the patients who have contributed to this very important research and to the British Thyroid Foundation for their support and input.
REC name
London - Hampstead Research Ethics Committee
REC reference
21/LO/0449
Date of REC Opinion
21 Jul 2021
REC opinion
Further Information Favourable Opinion