TOPLINE: 

Compared with placebo, secukinumab — an interleukin-17A inhibitor — did not show greater clinical efficacy in treating moderate-to-severe Graves' orbitopathy (GO); however, the drug was well tolerated, and no new safety signals were reported.

METHODOLOGY:

• The double-blind, multicentre ORBIT trial assessed the efficacy and safety of secukinumab in patients with active, moderate-to-severe GO.
• Overall, 28 patients with a clinical activity score ≥ 4 were randomly assigned to receive either 300 mg secukinumab (mean age, 53.6; 64.3% women) or placebo (mean age, 57.7; 85.7% women) subcutaneously for 16 weeks; patients who did not achieve a proptosis response proceeded to a subsequent 16-week open-label treatment phase.
• The primary outcome was the proportion of patients achieving an overall response — defined as a reduction of ≥ 2 points in the clinical activity score and a ≥ 2 mm reduction in proptosis from baseline, without deterioration in the fellow eye — after 16 weeks of treatment.
• Secondary outcomes included responder rates for proptosis, diplopia, and clinical activity score; changes in disease severity based on the European Group on GO guidelines; and the safety profile.
• Levels of thyroid-related hormones and autoantibodies were measured from serum samples.

TAKEAWAY:

• At 16 and 32 weeks, no patient in the secukinumab or placebo group achieved an overall response; no meaningful improvement was observed in proptosis, diplopia, or clinical activity scores during either treatment period.
• No significant improvement in disease severity was observed from baseline to 16 weeks in either treatment group.
• Secukinumab also failed to improve thyroid metabolic parameters.
• The drug was well tolerated; most adverse events were mild, and no treatment‑related discontinuations or new safety signals were reported.

IN PRACTICE:

"[Our study] findings indicate that blocking a single cytokine does not sufficiently limit the complex, multifactorial inflammatory processes involved in GO," the authors wrote.

SOURCE:

The study was led by Jan Wolf, Department of Medicine I, Johannes Gutenberg-University Medical Center, Mainz, Germany. It was published online on December 9, 2025, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size limited the study's statistical power and its ability to detect the effect of the intervention. Variables influencing outcome parameters could not be evaluated in detail due to the small sample size. The study's open-label extension phase may have introduced expectation bias, particularly influencing quality of life.

DISCLOSURES:

The study was supported by Novartis Pharma AG, Basel, Switzerland. Five authors declared being employees of and/or holding stock options in Novartis. Additionally, some authors declared receiving investigator fees, consulting fees, honoraria, support for attending meetings and/or travel, compensation for participation on data safety monitoring or advisory boards, or research funding or having other ties with several sources, including Novartis.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.