Tofacitinib for steroid‑resistant moderate-to-severe thyroid eye disease

A Single-Arm, Open-Label, Exploratory Study of Tofacitinib in Patients With Glucocorticoid-Resistant or Intolerant Moderate-to-Severe Active Thyroid Eye Disease

This will test whether taking oral tofacitinib (5 mg twice daily) for 24 weeks can reduce eye bulging and inflammation in adults with moderate-to-severe thyroid eye disease who don't respond to or cannot take high-dose steroids.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Xiamen University (other)
• Drugs / interventions: Teprotumumab, Rituximab, Tocilizumab, Tofacitinib
• Locations: 1 site (Xiamen, Fujian)
• Trial ID: NCT07547930 on ClinicalTrials.gov

What this trial studies

This phase 2, single-site interventional study gives oral tofacitinib 5 mg twice daily for 24 weeks to adults with active, moderate-to-severe thyroid eye disease who are glucocorticoid‑resistant or glucocorticoid‑intolerant. Key eligibility includes age 18–75, a Clinical Activity Score (CAS) ≥3, and prior failure of or contraindication to high‑dose IV glucocorticoids (≥3 g cumulative methylprednisolone or equivalent). Clinical assessments occur at baseline, weeks 4, 12, 24, and a follow-up at week 36, with primary outcomes focused on reductions in proptosis and CAS and safety monitoring. Exploratory laboratory and imaging measures will examine effects on inflammatory and tissue‑remodeling pathways tied to JAK‑STAT signaling.

Who should consider this trial

Good fit: Adults 18–75 years with active moderate-to-severe TED (CAS ≥3) who have failed to respond to at least 3 g IV methylprednisolone (or equivalent) or who have documented contraindications to high‑dose steroids are the intended participants.

Not a fit: Patients with sight‑threatening or inactive/mild disease, or those with contraindications to JAK inhibitors such as active serious infection, are unlikely to benefit from this treatment approach.

Why it matters

Potential benefit: If successful, tofacitinib could offer an oral rescue option that reduces proptosis, pain, and inflammation in patients who cannot be helped by or cannot tolerate steroids.

How similar studies have performed: Small case series and related JAK‑inhibitor reports have shown promising signals in TED, but randomized or larger controlled data for tofacitinib in steroid‑resistant TED remain limited.

Eligibility criteria

Inclusion Criteria:

1. Age and Gender: Male or female participants aged 18 to 75 years (inclusive).
2. Diagnosis: Clinical diagnosis of Graves' orbitopathy (GO) consistent with EUGOGO criteria.
3. Severity: Moderate-to-severe GO as defined by EUGOGO guidelines (impact on daily life, but not sight-threatening).
4. Activity: Active disease, defined as a Clinical Activity Score (CAS) \>=3 points (on the 7-point scale).
5. 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.
6. Thyroid Function: Euthyroid or mild hypothyroidism/hyperthyroidism maintained on stable antithyroid drugs or thyroxine replacement therapy for at least 4 weeks prior to baseline.
7. 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.
8. Consent: Willing and able to provide written informed consent and comply with study procedures.

Exclusion Criteria:

* 1.Sight-Threatening Disease: Presence of Dysthyroid Optic Neuropathy (DON) or severe corneal breakdown requiring immediate surgical intervention.

  2.Chronic/Inactive Disease: Fibrotic or burnout stage of GO with a Clinical Activity Score (CAS) \< 3.

  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.

  4.Concomitant Immunomodulation: Use of other biologic agents (e.g., Teprotumumab, Rituximab, Tocilizumab) within 3 months prior to baseline.

  5.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.

  6.Thrombosis Risk: History of venous thromboembolism (VTE), including deep vein thrombosis (DVT) or pulmonary embolism (PE), or known coagulation disorders.

  8.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).

  9.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

Where this trial is running

Xiamen, Fujian

• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (RECRUITING)

Study contacts

• Principal investigator: Fangsen Xiao, MD — The First Affiliated Hospital of Xiamen University
• Study coordinator: Fangsen Xiao, MD

Conditions: Thyroid Eye Disease, TED, Graves Ophthalmopathy, Graves Orbitopathy, Tofacitinib, Refractory Thyroid Eye Disease, Graves' Orbitopathy, JAK Inhibitor, Steroid-resistant