Early Use of Steroid-Sparing Agents in the Inactivation of Moderate-to-Severe Active Thyroid eye Disease

A Step-Down Approach

Zuzana Sipkova; Elizabeth A. Insull; Joel David; Helen E. Turner; Shay Keren; Jonathan H. Norris


Clin Endocrinol. 2018;89(6):834-839. 

In This Article

Subjects and Methods

Study Design and Patients

We performed a retrospective consecutive audit review of medical records of 104 patients who were treated by the Oxford multidisciplinary thyroid eye disease (TED) team (OxTED)[11] between 1st March 2013 and 31st August 2016. Patients with VISA inflammatory index score of three or more (Table 1) were classified as having 'active' inflammation[12,13] and were included in the audit.

Treatment modality, disease activity, and any adverse effects were reviewed at initial presentation and at 6- and 12-month follow-up after the commencement of treatment.

Treatment Protocol

All patients presenting to the OxTED clinic with a VISA inflammatory index score of 3 or more on the 10 point scale (Table 1) are routinely commenced on an SSA with adjunctive IVMP, typically 500 mg weekly for three doses (Figure 1). Methotrexate is our preferred first-line SSA (if not contraindicated) and is initiated at the same time as IVMP infusions at a dose of 20–25 mg per week, orally or subcutaneously, along with folic acid supplementation.

Figure 1.

Flow chart of immunosuppressant agents received by patients [Colour figure can be viewed at wileyonlinelibrary.com]

Second and third-line SSAs (ciclosporin and azathioprine) are added if there is insufficient clinical response or adverse effects or if methotrexate is contraindicated. Patients with good response but with persistent active TED receive three further doses of IVMP over the following 3 weeks.

To prevent steroid-induced gastritis, all patients are given omeprazole 20 mg/day while receiving IVMP treatment. Patients also receive bone protection with oral bisphosphonate, alendronate, and vitamin D3.

Evaluation Before SSAs

Pretreatment investigations included blood tests (full blood count, liver, and renal function tests). Additional investigations were performed depending on the type of SSA used. Chest X-ray was performed prior to starting treatment with methotrexate and thiopurine methyltransferase (TPMT) enzyme activity with azathioprine. Hepatitis and HIV serology, B-cell subsets and immunoglobulin electrophoresis is performed prior to rituximab. Full blood count and liver function was monitored in all patients on methotrexate every 2 weeks for the first 3 months and monthly thereafter.

Statistical Analysis

The data were analysed using Microsoft Excel 2013 (Microsoft Corporation, Redmond, WA). Student's t-test was used to compare pre- and post-treatment VISA inflammatory index scores. Values of P < 0.05 were considered to be statistically significant.