Tofacitinib for Glucocorticoid-Resistant Moderate-to-Severe Thyroid Eye Disease

NCT07547930 | Recruiting Phase 2

• 1 other identifier: XMFHIIT-2026SL001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Thyroid Eye Disease (TED), also known as Graves' orbitopathy, is an autoimmune condition that causes inflammation and tissue expansion behind the eyes, leading to bulging eyes (proptosis), double vision, and pain. Currently, intravenous glucocorticoids (steroids) are the standard first-line treatment. However, approximately 20-30% of patients do not respond to steroids, or cannot tolerate their side effects. This study aims to evaluate the safety and efficacy of Tofacitinib, an oral medication known as a Janus kinase (JAK) inhibitor, as a rescue therapy for these difficult-to-treat cases. Tofacitinib works by blocking specific signaling pathways (JAK-STAT) that drive inflammation and fibrosis in the eye socket. In this study, patients with moderate-to-severe active TED who are resistant to or intolerant of steroids will receive Tofacitinib tablets (5 mg twice daily) for 24 weeks. The researchers will assess whether the treatment can effectively reduce eye bulging and improve clinical activity scores.

Conditions

Thyroid Eye Disease, TED; Graves Ophthalmopathy; Graves Orbitopathy

Keywords

Tofacitinib; Refractory Thyroid Eye Disease; Graves' Orbitopathy; JAK Inhibitor; Steroid-resistant; Glucocorticoid-resistant

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Percentage of participants classified as responders in the study eye. A responder is defined as a patient who achieves at least one of the following criteria without deterioration in the fellow eye: (1) Reduction in proptosis\>=2 mm; (2) Reduction in Clinical Activity Score (CAS) \>= 2 points (on a 7-point scale).

  Week12，24

Secondary Outcomes (5)

• Change in Proptosis

  Baseline, Week 4, 12, 24, and 36

• Change in Clinical Activity Score (CAS)

  Baseline, Week 4, 12, 24, and 36

• Diplopia Response

  12W,24W

• Change in Graves' Orbitopathy Quality of Life (GO-QOL) Score

  Baseline and Week4，12，24，36

• Incidence of Adverse Events

  From baseline through Week 36

Study Arms (1)

Tofacitinib Treatment Group

EXPERIMENTAL

Participants in this arm will receive oral Tofacitinib Citrate (5 mg) twice daily (BID) for a total treatment duration of 24 weeks. Following the 24-week treatment period, participants will undergo a 12-week drug-withdrawal observation phase to monitor for disease relapse and safety.

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

5 mg tablet administered orally twice daily (BID) for a continuous period of 24 weeks.

Tofacitinib Treatment Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age and Gender: Male or female participants aged 18 to 75 years (inclusive).
• Diagnosis: Clinical diagnosis of Graves' orbitopathy (GO) consistent with EUGOGO criteria.
• Severity: Moderate-to-severe GO as defined by EUGOGO guidelines (impact on daily life, but not sight-threatening).
• Activity: Active disease, defined as a Clinical Activity Score (CAS) \>=3 points (on the 7-point scale).
• Refractory Status (Must meet ONE of the following):Glucocorticoid-Resistant: Failure to respond (no significant improvement in proptosis or CAS) after receiving a cumulative dose of at least 3g of intravenous methylprednisolone (or equivalent).Glucocorticoid-Intolerant: Documented contraindications to high-dose systemic glucocorticoids (e.g., uncontrolled diabetes mellitus, severe osteoporosis, glaucoma, severe psychiatric disorders) or history of severe adverse events leading to discontinuation.
• Thyroid Function: Euthyroid or mild hypothyroidism/hyperthyroidism maintained on stable antithyroid drugs or thyroxine replacement therapy for at least 4 weeks prior to baseline.
• Contraception: Women of childbearing potential must agree to use effective contraception during the study period and for at least 4 weeks after the last dose of the study drug.
• Consent: Willing and able to provide written informed consent and comply with study procedures.

You may not qualify if:

• Sight-Threatening Disease: Presence of Dysthyroid Optic Neuropathy (DON) or severe corneal breakdown requiring immediate surgical intervention.
• Chronic/Inactive Disease: Fibrotic or burnout stage of GO with a Clinical Activity Score (CAS) \< 3.
• Prior Orbital Treatment:Orbital radiotherapy at any time.Orbital surgical decompression at any time.Strabismus surgery or eyelid surgery within 3 months prior to baseline.
• Concomitant Immunomodulation: Use of other biologic agents (e.g., Teprotumumab, Rituximab, Tocilizumab) within 3 months prior to baseline.
• Active Infection Risk (Critical for JAK Inhibitors):Active tuberculosis (TB) or untreated latent TB.Active or chronic Hepatitis B or Hepatitis C infection.Human Immunodeficiency Virus (HIV) infection.History of disseminated herpes zoster or herpes simplex.Any severe active infection requiring hospitalization or IV antibiotics within 4 weeks of baseline.
• Thrombosis Risk: History of venous thromboembolism (VTE), including deep vein thrombosis (DVT) or pulmonary embolism (PE), or known coagulation disorders.
• Malignancy: History of any malignancy within the past 5 years (except adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix).
• Laboratory Abnormalities:Absolute Neutrophil Count (ANC) \< 1.0 \*10\^9/L and/or Absolute Lymphocyte Count (ALC) \< 0.5 \*10\^9/L and /or Hemoglobin \< 90 g/L and/or AST or ALT \> 2\* Upper Limit of Normal (ULN) and/or Estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min/1.73 m²

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Study Sites (1)

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

RECRUITING

Related Publications (4)

• Kim W, Seo MK, Kim YJ, Choi SH, Ku CR, Kim S, Lee EJ, Yoon JS. Role of the suppressor of cytokine signaling-3 in the pathogenesis of Graves' orbitopathy. Front Endocrinol (Lausanne). 2025 Mar 4;16:1527275. doi: 10.3389/fendo.2025.1527275. eCollection 2025.

  PMID: 40104138 BACKGROUND

• Ghahvehchian H, Eshraghi B. Tofacitinib for Refractory Thyroid Eye Disease. JAMA Ophthalmol. 2025 Dec 1;143(12):1073-1075. doi: 10.1001/jamaophthalmol.2025.3974.

  PMID: 41165674 BACKGROUND

• Wiersinga WM, Eckstein AK, Zarkovic M. Thyroid eye disease (Graves' orbitopathy): clinical presentation, epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2025 Jul;13(7):600-614. doi: 10.1016/S2213-8587(25)00066-X. Epub 2025 May 2.

  PMID: 40324443 BACKGROUND

• Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marino M, Vaidya B, Wiersinga WM; EUGOGO dagger. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. doi: 10.1530/EJE-21-0479.

  PMID: 34297684 BACKGROUND

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Study Officials

• Fangsen Xiao, MD

  The First Affiliated Hospital of Xiamen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fangsen Xiao, MD

CONTACT

+86-592-2137710; xfs888@163.com

Liyin Wang, MM

CONTACT

+86-592-2137710; wlywly1979@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, single-center, single-arm, open-label study. All eligible participants will be assigned to the treatment group to receive oral Tofacitinib Citrate (5 mg, twice daily) for a duration of 24 weeks. There is no concurrent control group. Efficacy endpoints will be assessed by comparing post-treatment data with baseline measurements (self-controlled design). After the 24-week treatment phase, participants will undergo a 12-week drug-withdrawal observation period to monitor for disease relapse.

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: April 23, 2026
• Study Start: April 24, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)