Teprotumumab N01 Versus Methylprednisolone After Urgent Orbital Decompression for Dysthyroid Optic Neuropathy

Inclusion Criteria:

• Able and willing to provide written informed consent.
• Age 18 to 65 years.

• Clinical diagnosis of thyroid eye disease (TED) with dysthyroid optic neuropathy (DON). Diagnosis of DON must meet both of the following criteria:

  1. Visual dysfunction not explained by other causes, such as decreased best-corrected visual acuity, visual field defect, abnormal color vision, or relative afferent pupillary defect.
  2. Imaging evidence of orbital apex crowding, optic nerve compression, or optic nerve stretching.

• The study eye meets the criteria for urgent orbital decompression, defined as either of the following:

  1. Poor response after rescue intravenous methylprednisolone for the current dysthyroid optic neuropathy episode, with a cumulative methylprednisolone-equivalent dose of no more than 3.0 g, defined as no improvement or continued deterioration of visual function within 1 to 2 weeks.
  2. Contraindication to glucocorticoids or investigator judgment that direct urgent mechanical decompression is required.
• Thyroid function is normal or mildly abnormal before enrollment, with free triiodothyronine (FT3) and free thyroxine (FT4) within 50% above or below the normal reference range when possible.
• Alanine aminotransferase (ALT) no more than 1.5 times the upper limit of normal, aspartate aminotransferase (AST) no more than 3 times the upper limit of normal, and serum creatinine no more than 1.5 times the upper limit of normal.
• For participants with diabetes mellitus, hemoglobin A1c (HbA1c) less than 9.0% and stable antidiabetic treatment within 60 days before enrollment.
• For women of childbearing potential, a pregnancy test must be negative before enrollment.
• Participants of reproductive potential agree to use effective contraception during the study and for 90 days after the last dose of study treatment.
• Able and willing to comply with study treatment and follow-up procedures.

Exclusion Criteria:

• Orbital decompression surgery within 6 months before screening.
• Bilateral dysthyroid optic neuropathy requiring urgent bilateral orbital decompression at baseline.
• Cumulative preoperative methylprednisolone-equivalent dose greater than 3.0 g for the current dysthyroid optic neuropathy episode.
• Systemic glucocorticoid treatment for non-thyroid eye disease within 3 months before screening with cumulative methylprednisolone-equivalent dose of 1.0 g or greater.
• Tocilizumab or other systemic immunosuppressive treatment within 3 months before screening, or rituximab within 6 months before screening.
• Orbital radiotherapy within 3 months before screening.
• Previous treatment with teprotumumab.
• Other ocular diseases that may significantly affect visual function assessment, including glaucomatous optic neuropathy, macular disease, severe cataract, or non-thyroid eye disease optic neuropathy.
• Irreversible optic nerve damage in the study eye with very low potential for visual recovery, as judged by the investigator.
• History of definite inner ear disease or clinically significant hearing impairment.
• Severe cardiovascular disease.
• Severe hepatic or renal disease.
• Active infection or clinically significant infectious disease, including active hepatitis, HIV infection, syphilis, or active tuberculosis.
• Active gastrointestinal ulcer.
• Clinically significant abnormal blood test results, including white blood cell count less than 4.0 × 10^9/L, platelet count less than 80 × 10^9/L, hemoglobin less than 110 g/L in males or less than 100 g/L in females.
• History of malignancy judged by the investigator to be unsuitable for enrollment.
• Pregnancy or breastfeeding.
• Known allergy to monoclonal antibodies, methylprednisolone, or any study drug excipient.
• Uncontrolled diabetes mellitus or any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.