Thyroid Eye Disease: Navigating the New Treatment Landscape

Abstract and Introduction

Abstract

Thyroid eye disease (TED) is a complex inflammatory disease that can have a long clinical course with sight-threatening and debilitating ocular sequelae. Until recently, there were limited therapeutic options available. In the last decade we have gained a deeper understanding of the underlying pathophysiology, which has led to the development of novel effective targeted therapies. This article discusses the challenges encountered in the clinical evaluation and treatment of TED patients, with the goal to empower endocrinologists and ophthalmologists to work together to provide effective multidisciplinary care. We will review recommendations of past clinical guidelines around evaluation and management of TED patients, discuss the randomized controlled trials of new biologic therapies, and explore how to navigate the emerging therapeutic landscape.

Table 1. Biologic therapies in active, moderate/severe thyroid eye disease
Therapy	Country, year	No.	Primary outcome	Treatment status	CAS < 3 after treatment, %	Improvement in proptosis^b	Improvement in diplopia^b	Adverse effects
RTX vs IV steroids (1000 mg IV every 2 wk × or 500 mg IV × 1)	Italy, 2015	32	% decrease CAS by ≥ 2 or with CAS < 3, 100% vs 69%, P = .043	Some with prior steroids	100% vs 69% at wk 24, P = .043	No	Yes with RTX in right eye at wk 24, P = .04	87% vs 63%, ^acytokine release syndrome, decrease of vision, infusion reaction
RTX vs placebo (1000 mg IV every 2 wk × 2)	USA, 2015	25	% decrease CAS by ≥ 2 or reduction in CAS, no difference compared with placebo	Some with prior steroids	31% vs 17% at wk 24, P = .41	No	No	62% vs 33%, ^ainfection, optic neuropathy, vasculitis
Tocilizumab vs placebo (8 mg/kg IV every 4 wk × 4)	Spain, 2018	32	% decrease CAS by ≥ 2, 93% vs 59%, P = .04	All steroid-resistant	87% vs 35% at wk 16, P = .005^c	–1.5 mm vs 0 at wk 16, P = .01^c	No	60% vs 24%, ^ainfection, headache, hypercholesterolemia, cytopenias
Teprotumumab vs placebo (10 mg/kg IV followed by 20 mg/kg IV every 3 wk × 8 doses total)	USA, 2017	88	% decrease CAS by ≥ 2 and proptosis decrease by ≥ 2 mm, 69% vs 20%, P < .001	Prior exposure to < 1 g methylprednisolone	69% vs 21%^d at wk 24, P < .001	–2.46 mm vs –0.15 mm, P < .001	68% vs 26% at wk 24, P < .001	74% vs 73%, ^anausea, muscle spasms, diarrhea, hyperglycemia. alopecia, headache, weight loss, hearing impairment
Teprotumumab vs placebo (10 mg/kg IV followed by 20 mg/kg IV every 3 wk × 8 doses total)	USA, 2020	83	Proptosis decrease by ≥ 2 mm, 83% vs 10%, P < .001	Prior exposure to < 1 g methylprednisolone	59% vs 21%^d at wk 24, P < .001	–3.32 mm vs –0.53 mm at wk 24, P < .05	68% vs 29% at wk 24, P = .001	85% vs 69%, ^amuscle spasms, alopecia, nausea, fatigue, diarrhea, headache

Table 1. Biologic therapies in active, moderate/severe thyroid eye disease

Therapy

Country, year

No.

Primary outcome

Treatment status

CAS < 3 after treatment, %

Improvement in proptosis^b

Improvement in diplopia^b

Adverse effects

RTX vs IV steroids (1000 mg IV every 2 wk × or 500 mg IV × 1)

Italy, 2015

% decrease CAS by ≥ 2 or with CAS < 3, 100% vs 69%, P = .043

Some with prior steroids

100% vs 69% at wk 24, P = .043

Yes with RTX in right eye at wk 24, P = .04

87% vs 63%, ^acytokine release syndrome, decrease of vision, infusion reaction

RTX vs placebo (1000 mg IV every 2 wk × 2)

USA, 2015

% decrease CAS by ≥ 2 or reduction in CAS, no difference compared with placebo

Some with prior steroids

31% vs 17% at wk 24, P = .41

62% vs 33%, ^ainfection, optic neuropathy, vasculitis

Tocilizumab vs placebo (8 mg/kg IV every 4 wk × 4)

Spain, 2018

% decrease CAS by ≥ 2, 93% vs 59%, P = .04

All steroid-resistant

87% vs 35% at wk 16, P = .005^c

–1.5 mm vs 0 at wk 16, P = .01^c

60% vs 24%, ^ainfection, headache, hypercholesterolemia, cytopenias

Teprotumumab vs placebo (10 mg/kg IV followed by 20 mg/kg IV every 3 wk × 8 doses total)

USA, 2017

% decrease CAS by ≥ 2 and proptosis decrease by ≥ 2 mm, 69% vs 20%, P < .001

Prior exposure to < 1 g methylprednisolone

69% vs 21%^d at wk 24, P < .001

–2.46 mm vs –0.15 mm, P < .001

68% vs 26% at wk 24, P < .001

74% vs 73%, ^anausea, muscle spasms, diarrhea, hyperglycemia. alopecia, headache, weight loss, hearing impairment

Teprotumumab vs placebo (10 mg/kg IV followed by 20 mg/kg IV every 3 wk × 8 doses total)

USA, 2020

Proptosis decrease by ≥ 2 mm, 83% vs 10%, P < .001

Prior exposure to < 1 g methylprednisolone

59% vs 21%^d at wk 24, P < .001

–3.32 mm vs –0.53 mm at wk 24, P < .05

68% vs 29% at wk 24, P = .001

85% vs 69%, ^amuscle spasms, alopecia, nausea, fatigue, diarrhea, headache

Thyroid Eye Disease: Navigating the New Treatment Landscape

Abstract and Introduction

Abstract

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