Teprotumumab for the treatment of chronic thyroid eye disease

Abstract

Background: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED.

Methods: In this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis.

Results: Thirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5 mm (0.4) and 3 mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011 mm³ (1847) in the study orbit and 1620 mm³ (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm³ (1681) in the study orbit and 1370 mm³ (1181) in the fellow orbit.

Conclusion: Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.

Fig. 1. Clinical measurements before and after Teprotumumab.

a Changes in exophthalmometry, the CAS and Gorman diplopia scores before and after therapy. b Changes to gaze restriction for each of the rectus muscles before and after Teprotumumab therapy.

Fig. 2. Changes to orbital soft tissue before and after Teprotumumab therapy.

a CT scan showing the extraocular muscles before and after completion of teprotumumab therapy in the same patient. b Extraocular muscle and orbital fat volume in each patient before and after Teprotumumab therapy.

Fig. 3. Clinical case.

Photograph at baseline and following treatment with teprotumumab.

Fig. 4. The role of orbital fibroblasts (OFs) in acute and chronic TED.

The IGF-1R is overexpressed on OFs in the acute and chronic phase. In the acute phase, activation of the IGF-1R/TSHR pathway leads to proliferation of inflammatory cytokines, production of hyaluronan and other extracellular matrix proteins and differentiation into adipocytes or myofibroblasts, resulting in tissue expansion. In the chronic phase, the overexpression of IGF-1R on OFs persists and maintains tissue expansion. RANTES regulated upon activation, normal T cell expressed, and secreted, also known as CCL5, HA hyaluronic acid, GAGs Glycosaminoglycans.