Combined immunosuppression and radiotherapy in thyroid eye disease

Takeaway

• In patients receiving a 24-week reducing course of oral corticosteroids, radiotherapy did not have added benefit.
• Benefits of adding azathioprine were less definitive but suggest improved clinical outcome at 48 weeks.

Why this matters

• New therapies for thyroid eye disease are needed, since corticosteroids are typically withdrawn after 24 weeks to limit cumulative toxic effects.
• Given that active disease lasts 1-2 years, recurrence at the time of withdrawal often occurs.

Key results

• There was improvement in binary clinical composite outcome measure with azathioprine vs placebo (aOR, 2.56; 95% CI. 0.98-6.66; P=.054).
• Orbital radiotherapy improved composite outcome measure vs sham radiotherapy (aOR, 0.89; 95% CI, 0.36-2.23; P=.80).
• No interaction was seen between azathioprine and radiotherapy (P_interaction=.86).
• Azathioprine with orbital radiotherapy did not offer additional advantage over azathioprine alone (P=.32).
• In all patients, ophthalmopathy index fell between week 12 and week 48 (P=.04), but did not differ between the treatment groups.
• 97 (91%) of 107 patients had improved clinical activity score (CAS) by week 12; 96 (98%) of 98 patients with CAS data at 48 weeks showed improvement.
• There was no difference in 12-week change in CAS between azathioprine and placebo, or radiotherapy and sham radiotherapy.
• No interaction was seen between azathioprine and radiotherapy in their effect on CAS (P_interaction=.48).
• There was no benefit in long-term Graves Ophthalmopathy Quality of Life visual function or appearance with azathioprine or orbital radiotherapy.

Study design

• Multicentre, double-blind, randomised controlled trial conducted at 6 UK centres.
• Adults (n=126) with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction received a reducing 24-week course of oral prednisolone and were randomly assigned to receive radiotherapy plus azathioprine (n=31), sham radiotherapy and azathioprine (n=31), radiotherapy and placebo (n=32) or sham radiotherapy and placebo (n=32).
• Funding: National Eye Research Centre; Above and Beyond; and Moorfields Eye Charity.

Limitations

• High rate of participant withdrawal.