Investigators examined the efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant Graves orbitopathy (GO).

Study design

This double-masked randomized clinical trial included 32 adults with moderate-to-severe corticosteroid-resistant GO who were randomized to either tocilizumab (8 mg/kg body weight) or placebo administered intravenously at weeks 0, 4, 8 and 12 with follow up for an additional 28 weeks. Investigators defined the primary outcome as the rate of patients who had a decrease in the clinical activity score (CAS) of 2 points from baseline to 16 weeks.

Outcomes

The primary outcome was met by 93.3% of patients receiving tocilizumab and 58.8% of those receiving placebo (P=0.04). Exophthalmos improved by a mean of 1.5 mm in the tocilizumab group and 0.0 mm in the placebo group (P=0.01). In the tocilizumab group, 1 patient experienced a moderate increase in transaminases at week 8, and another had an acute pyelonephritis at week 32.

Limitations

Thyroid eye disease is a heterogeneous disease with varying clinical courses between patients. Although this is a promising study in the evaluation of the anti-interleukin-6 receptor antibody tocilizumab for corticosteroid-resistant cases, the numbers are small and further studies are needed to truly examine tocilizumab’s efficacy and safety.

Clinical significance

A number of biologic agents have been investigated in the treatment of active thyroid eye disease. Promising results have been described with teprotumumab, rituximab, etanercept and adalimumab. Physicians should be aware that this study specifically looked at the efficacy of tocilizumab in steroid-resistant cases, which is a difficult population of patients to treat, but also a significant minority of patients with thyroid eye disease.