The Effect of Teprotumumab on Thyroid Eye Disease and Thyroid Dysfunction (Teprotumumab)

This protocol studies the clinical outcome of patients with active thyroid disease with visually significant signs and symptoms of proptosis, pain, diplopiam lid/orbital edema, or lid/orbital erythema recommended for treatment with teprotumumab infusion (Tepezza®). Patients recommended for treatment will be evaluated by an oculoplastic surgeon (Dr. Eva Chou) and endocrinologist (Dr. Thanh Hoang).

Study Overview

• Status: Recruiting
• Conditions: Thyroid Eye Disease; Graves Ophthalmopathy; Graves Disease
• Intervention / Treatment: Drug: Teprotumumab Injection [Tepezza]

Detailed Description

Thyroid eye disease (TED), also known as Graves' orbitopathy or thyroid-associated ophthalmopathy is a rare debilitating autoimmune condition in which immune cells attack the eye muscles and connective tissues within the eye socket, leading to proptosis, pain, diplopia, periorbital and orbital erythema and edema, exposure keratopathy and lagophthalmos, decreased vision, and compressive optic neuropathy. It has an incidence of 1.9 cases per 10,000 population per year. Approximately 25% of patients with autoimmune thyroid disease develop TED within 18 months of diagnosis. Severe optic neuropathy will affect 10% of patients with TED, leading to irreversible vision loss.

The natural history of TED involves an initial active phase, during which the autoimmune process causes the above mentioned morbidity, followed by a quiescent phase. The active period usually lasts 2-3 years and requires monitoring until the disease is quiescent. Until now, treatment during the active period focuses on preserving sight and providing treatment for double vision. Emergent orbital decompression or radiation treatment is reserved for compressive optic neuropathy. Alternative therapies, such as glucocorticoids, have little effect on proptosis and can have dose-limiting side effects. When the active phase "burns" out, the treatment for thyroid eye disease involves rehabilitative surgeries for orbital decompression, followed by strabismus surgery, followed by eyelid recession surgery; altogether, this may involve multiple surgeries which don't reverse the damage of the ocular and orbital tissues.

Tepezza®, or teprotumumab, is a fully human monoclonal insulin-like growth factor-1 receptor (IGF-1R) inhibitor antibody which blocks the inflammatory/autoimmune pathophysiology that underlies thyroid eye disease. It is the first FDA-approved medication for the treatment of adults with thyroid eye disease, reversing inflammatory changes of proptosis and diplopia. In clinical trials, 83% of patients receiving teprotumumab demonstrated a greater than 2 mm reduction in proptosis compared to 10% of participants who received placebo (between-group difference, 73% points; 95% CI = 59-88; P<0.001). Teprotumumab had a quick improvement on each outcome, which was evident at the first postbaseline evaluation at week 6, and the results improved during the 24-week treatment period. This therapy could potentially replace surgery for many patients, including those with more advanced disease.

The investigators propose a retrospective observational chart review of a cohort of adults with active TED without compressive optic neuropathy necessitating urgent orbital decompression or radiation who are undergoing treatment with Tepezza®. Inclusion criteria are patients with a clinical diagnosis of autoimmune thyroid disease and moderate-severe TED with clinical activity including symptoms of proptosis, diplopia, orbital pain, lid/orbital edema, or lid/orbital erythema, and with circulating thyroid stimulating or anti-thyroid auto-antibodies present within the last 18 months from the initiation of treatment. Exclusion criteria include patients with a history of compressive optic neuropathy necessitating urgent orbital decompression or external beam radiation, patients with a history of uncontrolled diabetes, uncontrolled inflammatory bowel disease, patients under 18 years old, and patients who are pregnant or trying to become pregnant.

The primary outcome is CAS score improvement and TSI level.

HLA has been associated with Graves disease and TED in different populations. In White patients, C*07:01, DQA1*05:01, DRB1*03, and DQB1*02:01 are associated with GD risk while DRB1*07:01 and DQA1*02:01 may be protective. However, in Asian patients, GD was noted to be mostly associated with B*46:01, *05:01, DRB1*08:02/03, DRB1*16:02, DRB1*14:03, DRB1*04:05, DQB*05:02 and DQB1*03:03, while DRB1*07:01 DRB1*01:01, DRB1*13:02, and DRB1*12:02 are potentially protective. Likewise, HLA-B*38:02, DRB1*16:02, DQA1*01:02, and DQB1*05:02 have been linked to increased TED risk in Asian patients while HLA-B*54:01 may be protective for TED in White patients.

In this study, the investigators analyze the HLA subtypes and correlate these with responders and non-responders to teprotumumab therapy.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: THANH D HOANG, DO; Phone Number: 6220 3012955165; Email: thanh.d.hoang.mil@health.mil
• Study Contact Backup: Name: Iris Morris, PhD; Phone Number: 3013194599; Email: iris.e.morris3.civ@health.mil

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Recruiting
      • Walter Reed National Military Medical Center
      • Contact: Thanh D Hoang, DO; Phone Number: 6220 301-295-5165; Email: thanh.d.hoang.mil@health.mil
      • Contact: Iris E Morris, PhD; Phone Number: 3013194599; Email: iris.e.morris3.civ@health.mil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study participants were 18-80 years old at the time of treatment with teprotumumab, diagnosed with autoimmune thyroid disease (positive stimulating thyroid receptor antibodies or elevated TSI), presenting with active eye disease (associated with at least one of the following: lid retraction of ≥2 mm, moderate or severe soft-tissue involvement, proptosis of ≥3 mm above the normal values for race and sex, and periodic or constant diplopia), and treated with at least one dose of teprotumumab.

Description

Inclusion Criteria:

• only DOD beneficiaries
• adult patients 18 years of age or older
• adult patients with proptosis, ocular/orbital pain, diplopia, lid/orbital edema, or lid/orbital erythema associated with autoimmune thyroid disease

Exclusion Criteria:

• Patients with evidence of compressive optic neuropathy necessitating urgent orbital decompression or external beam radiation
• patients with a history of uncontrolled diabetes mellitus
• patients with a history/diagnosis of uncontrolled inflammatory bowel disease
• patients under age 18 years
• patients who are pregnant or trying to become pregnant.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ophthalmological Clinical Activity Score (CAS) scoring	CAS scoring (1 to 10)	6-12 months post treatment
Thyroid stimulating immunoglobulin	TSI (IU/L)	6-12 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HLA subtypes	HLA subtypes	6-12 months

Collaborators and Investigators

• Sponsor: Walter Reed National Military Medical Center
• Investigators: Principal Investigator: Thanh D Hoang, DO, Walter Reed National Military Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Estimated): May 12, 2026
• Study Completion (Estimated): December 12, 2027

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: February 16, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Thyroid eye disease; Graves disease; Graves ophthalmopathy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases; Graves Disease
• Other Study ID Numbers: 20-10974

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes