SFEIES24 Oral Poster Presentations Oral Posters 1 – Endocrinology 1 (4 abstracts)
Immunomodulation of severe graves’ disease: graves’-plasma cell depletion (PCD) trial
Lydia Grixti 1,2 , Kathleen Allinson 2 , Faye Wolstenhulme 3 , James Wason 4 , Earn Gan 1,5 , Salman Razvi 6,2 , Kathryn Stewart 6 , Stuart Bennett 7 , Ahmed Al-Sharefi 8 , Satish Artham 8 , Ashwin Joshi 8 , Petros Perros 2 , Richard Quinton 1 , Catherine Napier 1 , Anna Mitchell 1 , Yaasir Mamoojee 1 & Simon H. Pearce 1,2
1Department of Endocrinology, Royal Victoria Infirmary NHS Newcastle Upon Tyne Hospitals, Newcastle Upon Tyne, United Kingdom; 2Translational and Clinical Research Institute, Newcastle University, BioMedicine West, Central Parkway, Newcastle Upon Tyne, United Kingdom; 3Newcastle Clinical Trials Unit, 1-4 Claremont Terrace, Newcastle University, Newcastle Upon Tyne, United Kingdom; 4Biostatistics Research Group, Population Health Sciences Institute, Newcastle University, Ridley Building 1, Queen Victoria Road, Newcastle Upon Tyne, United Kingdom; 5Honorary Clinical Senior Lecturer; Newcastle University, Newcastle Upon Tyne, United Kingdom; 6Gateshead Health NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom; 7Northumbria Healthcare NHS Foundation Trust, North Tyneside and Northumberland, United Kingdom; 8South Tyneside and Sunderland NHS Foundation Trust, Sunderland, United Kingdom
Introduction: Hyperthyroid Graves’ Disease affects 3% of women and 0.5% of men over a lifetime, with only 50% of patients experiencing remission following antithyroid drug therapy. The humoral immune response involves the production of Thyroid Stimulating Hormone Receptor antibodies (TRAbs) from plasma cells. This study aims to provide proof of principle that Daratumumab, a monoclonal antibody targeting cell-surface CD-38 on plasma cells, could modulate the immune response in Graves’ disease compared to conventional anti-thyroid drug therapy alone.
Method: 30 patients with severe Graves’ disease were recruited across this 2-stage clinical trial. All patients had newly diagnosed or relapsed Graves’ disease within the previous 12 months, with FT4≥50 pmol/l and TRAb levels >10IU/l. Patients were randomised to placebo or different doses of daratumumab. Follow up visits were scheduled at 4,6,12 and 24 weeks with changes in serum TRAb as the primary outcome.
Results: The cohort had a male to female ratio of 8:22 of a mean age of 41yrs and mean TRAb level at screening of 56.5U/l. 13 patients randomised to the highest doses of Daratumumab (9 mg/kg and 16 mg/kg), showed a median TRAb reduction of 72% at week 12, compared to 51% in the placebo group. All patients receiving Daratumumab, experienced reductions in immunoglobulins IgA (79%) >IgM (54%)>IgG (37%) by 6 weeks. Compared to total IgG, a more potent reduction in TRAb antibodies was observed, suggesting that thyroid plasma cells actively involved in the autoimmune response were preferentially targeted by daratumumab.
Conclusion: This study demonstrates proof of principle that Daratumumab can modify the immune response in Graves’ disease. Continued patient follow-up is necessary to determine whether this will translate to improve the chances of remission in severe Graves’ Disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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