Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening autoimmune disease that can be categorized into mild, moderate, and severe stages based on severity. The activity of TAO is commonly evaluated using the Clinical Activity Score (CAS). Tocilizumab serves as a second-line treatment option for patients with moderate to severe active TAO. Additionally, it is common for TAO patients to experience anxiety, which may exacerbate their condition and negatively impact prognosis. Therefore, we have designed this randomized controlled study to evaluate the impact of Flupentixol Melitracen (Lepan) on the treatment outcomes of participants receiving Tocilizumab (Actemra).
Aged between 18 and 80 years (inclusive).
Meets internationally recognized diagnostic criteria for TED with the more severely affected eye in moderate to severe active phase. Meeting any one of the following criteria qualifies as moderate to severe: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm. A Clinical Activity Score (CAS) of ≥3 or a score of 2 combined with MRI evidence indicating active disease is defined as active.
Normal thyroid function within one month prior to enrollment: including those currently taking antithyroid drugs or not requiring medication, with FT3 and FT4 levels within normal range and TSH either normal or decreased.
HAMA (Hamilton Anxiety Rating Scale) score of ≥14.
Severe cardiac, hepatic, or renal insufficiency (including myocardial ischemia or myocardial infarction, arrhythmias, and heart failure; ALT, AST ≥ 3 times the upper limit of normal; eGFR < 60 ml/min/1.73 m²).
communicable disease.
Pregnancy or planning to become pregnant.
Currently breastfeeding.
Parallel
Tocilizumab(400mg) combined with Flupentixol Melitracen(0.5mg:10mg)
DrugTocilizumab (Actemra) is administered via intravenous infusion at a dose of 400 mg at Weeks 0, 4, and 8. Flupentixol/Melitracen is given orally at a dose of 0.5 mg/10 mg twice daily for 8 consecutive weeks starting from Week 0.
Tocilizumab(400mg)
DrugTocilizumab (Actemra) is administered via intravenous infusion at a dose of 400 mg at Weeks 0, 4, and 8.
comprehensive score
The comprehensive score has a maximum of 30 points. It is calculated as follows：the half score of TED-QoL (Thyroid Eye Disease Quality of Life questionnaire) (15 points), plus the higher value of CAS (Clinical Activity Score) between the two eyes (7 points). Additionally, one point is added for each symptom present in the participant: tearing, photophobia, dry eye, blurred vision. Also included are diplopia score (3 points) and restricted eye movement score (1 point). The study investigates changes in the comprehensive score before and after treatment in two groups.
Go-qol
The change from baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire visual function score and psychosocial function score, and the total score.
TED-QoL
The change from baseline in the TED-QoL.
CAS Decrease by ≥2 Points
The proportion of participants whose higher CAS value decreased by ≥2 points compared to baseline.
CAS Change Value
The change in CAS value compared to baseline for participants.
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