Effects of teprotumumab and role of HLA markers in patients with thyroid eye disease.

Objective: To evaluate the effects of teprotumumab on ophthalmological and biochemical findings and assess potential genetic markers for TED responses.

Methods: This is a retrospective study. Participants were 18-76 years old. All subjects were treated with teprotumumab. The primary outcome was the change in proptosis before and after teprotumumab treatment. Secondary outcomes include change in other ophthalmic measures and thyroid laboratory tests. Human leukocyte antigens (HLA) were also analyzed as markers for response to teprotumumab.

Results: Twenty-six patients were included in the final analysis. There was a significant decrease in TSI and TRAb levels and significant increases in HbA1c, fasting glucose, and total T3 levels. There was also significant reduction in proptosis, clinical activity score (CAS), retinal nerve fiber layer (RNFL) thickness, ganglion cell thickness (GCA), and intraocular pressure (IOP). HLA haplotypes were distinct between responders and non-responders, with HLA-DRB3*02:02:01G, HLA-DRB4*neg, and HLA-DQB1*02:01:01G demonstrating better response to teprotumumab and HLA-A*23:01:01G strongly correlating to non-response.

Conclusions: Patients with both acute and chronic TED treated with teprotumumab had a significant reduction in TSI and TRAb levels and improvement in proptosis, CAS, RNFL and GCA thickness, and IOP. HLA may predict responders vs. non-responders. Further studies with longer duration and larger population comparing teprotumumab with steroids or other immunomodulatory agents (tocilizumab, rituximab, etc) may be helpful.