ESPE Abstracts

Moderate to severe Graves ophthalmopathy (GO) is rare in children and most patients have mild GO. This complex inflammatory autoimmune disorder affecting the orbital fat and muscles is linked to circulating TSH receptor antibodies and involves the insulin-like growth factor-I receptor (IGF-IR) on orbital fibroblasts. Severe GO features include proptosis, diplopia and vision loss. Intravenous glucocorticoid pulse therapy is the first line medical treatment for moderate to severe GO but about 30% of patients are corticosteroid resistant. Other medical treatments such as rituximab or tocilizumab have been proposed with limited efficacy. More recently, teprotumumab (TEP), a human IGF-IR inhibitory monoclonal antibody has demonstrated significant efficacy in adult patients with severe GO and is approved in several countries since 2020. Mild to moderate side effects have been described and safety reports are still under investigation. We described the first pediatric patient with active corticosteroid-resistant GO treated with TEP. Graves’ disease occurred at the age of 13 yr. with initially mild GO. After 16 months of treatment with carbimazole, GO became active with conjunctival redness, increased proptosis and diplopia. Intravenous glucocorticoid pulse therapy during 7 weeks (cumulative dose = 6 g) was used and active signs of GO decreased. Six months later, GO became active again and resistant to corticosteroids. He received 5 infusions of TEP (10 then 20mg/kg, 3 weeks apart). TRAb were negative before start of TEP. Redness disappeared after the first infusion, with clinical activity score (CAS) decreasing from 5 to 1 and proptosis significantly decreasing by 5 mm changing GO grade from 3 to 1 (MRI data). A sudden coma occurred after the 5th infusion and the patient received 3 days of noninvasive artificial ventilation. All investigations were normal and ruled out other causes of impaired consciousness, in particular toxic, infectious or autoimmune. No haplotype of susceptibility to Graves' disease, autoimmune encephalitis or TED was found (HLA). The patient remained with lethargic state associated with dysgeusia and sensory hallucinations for several weeks. After a few months, a spontaneous clinical improvement occurred but concentration issues are still present. TEP was stopped after the occurrence of neurological manifestations and GO has remained stable with a 14 month follow-up. In conclusion TEP was efficient in an adolescent with severe corticosteroid resistant GO. The role of TEP in the severe neurological manifestations observed cannot be ruled out given the chronology and the safety profile of TEP in adult patients.