Active Moderate-to-Severe Thyroid Eye Disease in Graves’ Disease — Next-Line Management After Intravenous Glucocorticoids

In Graves’ disease, active moderate-to-severe thyroid eye disease (TED) can persist or worsen despite first-line therapy. When initial treatment has not achieved the required clinical milestones at 24 weeks, a structured next-line protocol applies.

Clinical Scenario

Patients with Graves’ disease presenting with clinically active, moderate-to-severe thyroid eye disease — characterised by significant orbital inflammation with features such as proptosis and diplopia. Intravenous glucocorticoids combined with mycophenolate mofetil represent established first-line therapy for this presentation, per the 2021 EUGOGO Clinical Practice Guidelines.

First-Line Treatment — Insufficient Response

Prior regimen: Intravenous glucocorticoids (methylprednisolone) combined with mycophenolate mofetil.

Targets not achieved at 24 weeks: Improvement in Clinical Activity Score (CAS), reduction in proptosis, and improvement in diplopia, visual acuity, and soft tissue swelling.

Next-Line Approach

This protocol specifies targeted intravenous biologic therapy, with agent selection guided by the clinical context. The complete regimen, sequencing, and monitoring criteria are available in the full protocol.

Treatment Goals

Improvement of Clinical Activity Score (CAS) by at least 2 points and reduction in proptosis by at least 2 mm.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.ecl.2021.12.004.

Intravenous glucocorticoids (IVGC) are considered first-line therapy in patients with moderate-to-severe TED.

The 2021 EUGOGO Clinical Practice Guidelines recommend combined use of IVGC and mycophenolate as first line therapy for active moderate-severe TED.

Teprotumumab is administered intravenously every 3 weeks (10 mg/kg first dose, then 20mg/kg) for a total of 8 infusions.

Dosing is 8 mg/kg at four monthly infusions.

A randomized trial of 32 patients with moderate-to-severe corticosteroid-resistant TED randomly assigned patients to tocilizumab (8 mg/kg) or placebo, administered intravenously at weeks 0, 4, 8, and 12.

For treatment of TED, two infusions of rituximab (1000 mg each and 2 weeks apart) have been utilized without immunosuppressive effects.

In the first trial, improvement of CAS by ≥ 2 points and reduction in proptosis by ≥ 2 mm, together, occurred in 69% of patients with teprotumumab versus 20% with placebo.

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