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


104 cases of TED were reviewed and 24 patients (12 males, 12 females; mean age 46.8 years (range: 23–84 years)) were included in the audit. The baseline patient characteristics are summarised in Table 2. All 24 patients received IVMP with mean cumulative dose of 2.72 g (range: 1.0–6.9 g). 38% of patients (n = 9) received 1.5 g IVMP or less. Only two patients required more than 4.5 g of IVMP equating to the EUGOGO treatment protocol dose for this patient group (Figure 2).[4] The average number of doses was seven (range 3–18 total doses). No patients received oral corticosteroids.

Figure 2.

Total intravenous methylprednisolone (IVMP) dose received by individual patients [Colour figure can be viewed at wileyonlinelibrary.com]

MTX was given either orally or subcutaneously in 23 (96%) patients as first-line SSA. One patient received azathioprine due to chronic lung disease findings on chest X-ray (Figure 1). Twenty patients started on 20 mg weekly oral dose, four of whom were later increased to a 25 mg weekly subcutaneous dose. The subcutaneous route of administration reduces gastro-toxicity symptoms in some patients. Four patients received 25 mg weekly subcutaneous doses first-line. The average MTX treatment course was 13 months (range: 2–27 months). Eleven patients (42%) received a second SSA, ciclosporin in most cases (Figure 1). A third agent, in addition to methotrexate and ciclosporin, was required in three patients: Rituximab in two cases and Azathioprine in one. Methotrexate was continued in all cases.

The mean pretreatment VISA inflammatory index score was 5.5 of 10 (range: 1–9; Figure 3). There was significant improvement in this score both at the intermediate review (mean score 2.7; SD = 2.8; P < 0.001; mean follow-up 25.2 weeks) and at last follow-up (mean score 1.4; SD = 1.5; P < 0.001; mean follow up 48.0 weeks).

Figure 3.

Mean VISA inflammatory index score at presentation, 6- and 12-month follow up. Error bars represent 95% confidence intervals. Asterisks (*) represent statistically significant improvement in VISA score compared to score at presentation, P < 0.001 [Colour figure can be viewed at wileyonlinelibrary.com]

Four patients did not show adequate clinical improvement despite high dose IVMP and two or more SSAs and required orbital decompression due to signs of dysthyroid optic neuropathy. This included one patient who could not have MTX due to chronic lung disease and second patient who stopped MTX after 3 months due to chronic cough.

No serious or long-term adverse effects were reported. Three (13%) patients stopped methotrexate due to: deranged liver function tests, chronic cough or recurrent cystitis (Figure 4), all of which resolved on cessation of the methotrexate. None of the patients developed leucopenia.

Figure 4.

Adverse effects in patients taking methotrexate [Colour figure can be viewed at wileyonlinelibrary.com]