Teprotumumab reduces proptosis in long-standing, stable thyroid eye disease
Click Here to Manage Email Alerts
Key takeaways:
- Teprotumumab reduces proptosis by 2 mm or more for most adults with long-standing thyroid eye disease and low clinical activity scores.
- Safety data in the study were consistent with prior teprotumumab trials.
Adults with long-standing thyroid eye disease and low clinical activity scores had greater reductions in proptosis with teprotumumab compared with placebo, according to data published in The Journal of Clinical Endocrinology & Metabolism.
As Healio previously reported, the FDA approved teprotumumab-trbw (Tepezza, Horizon Therapeutics) in January 2020 for the treatment of thyroid eye disease after trials found the agent reduced proptosis for adults who were recently diagnosed with thyroid eye disease and those with a high clinical activity score. New data from a phase 4 trial found teprotumumab conferred similar proptosis reductions for adults with long-standing thyroid eye disease and a low clinical activity score of 1 or less.
“Now patients with thyroid eye disease, no matter duration or activity level, have been shown to benefit from teprotumumab,” Raymond Douglas, MD, PhD, an oculoplastic surgeon and director of the orbital and thyroid eye disease program at Cedars-Sinai Medical Center, told Healio. “This allows physicians and patients to determine if the treatment is right for them.”
Douglas and colleagues conducted a randomized, double-masked, placebo-controlled phase 4 trial at 11 sites in the U.S. Adults aged 18 years and older with thyroid eye disease duration of 2 to 10 years were enrolled. Participants were required to have a clinical activity score of 1 or less in both eyes or have no proptosis progression, diplopia progression and no new inflammatory symptoms in the year before enrollment. Adults were randomly assigned, 2:1, to eight infusions of teprotumumab or placebo every 3 weeks for 24 weeks. The primary outcome was the change in proptosis from baseline to 24 weeks. Researchers also examined the percentage of adults with a proptosis reduction of 2 mm or more during the study, change in diplopia and change in Graves’ Ophthalmopathy Quality of Life (GO-QOL) appearance and visual functioning subscales.
There were 58 adults who completed the study, with 39 in the teprotumumab group and 19 in the placebo group. In the intent-to-treat analysis, the teprotumumab group had a 2.41 mm reduction in proptosis from baseline to 24 weeks compared with a 0.92 mm reduction with placebo (P = .0004). A higher percentage of participants in the teprotumumab group had a proptosis reduction of 2 mm or more compared with placebo (61.9% vs. 25%; P = .0134). No differences in diplopia improvement were observed between the two groups.
“This study very clearly shows that patients with the disease, despite the amount of inflammation and the duration of disease, derive significant benefit from teprotumumab,” Douglas said.
The teprotumumab group had a greater improvement in GO-QOL visual function subscale compared with placebo. However, there was no difference for change in the appearance-related subscale between the two groups.
Of six adults receiving teprotumumab who had an orbital MRI performed at baseline week 24, improvements in proptosis were accompanied with a 24.95% mean decrease in retro-orbital total muscle volume, a 24.31% decrease in inferior rectus volume, a 20.07% reduction in superior rectus volume, a 15.1% decrease in medial rectus volume and a 28.85% reduction in lateral rectus volume. Orbital fat volume decreased by 34.63% among the subgroup.
A similar percentage of adults in the teprotumumab and placebo groups reported adverse events. Adverse events that were more common with teprotumumab than placebo included muscle spasms (41.5% vs. 10%), fatigue (22% vs. 10%), headache (17.1% vs. 10%), dry skin (12.2% vs. 0%), eye pain (12.2% vs. 5%), eye pruritus (7.3% vs. 0%), HbA1c increase (7.3% vs. 0%) and hypertension (7.3% vs. 0%). Those adverse events were all mild to moderate in severity. Serious adverse events were reported by one person in each group.
Douglas said future research is needed to answer more questions on the utility of teprotumumab in treating thyroid eye disease.
“Further research into reactivation of disease and successful treatment with repeat dosing would allow additional insight,” Douglas said.
For more information:
Raymond Douglas, MD, PhD, can be reached at raymonddouglasmd@gmail.com.
Perspective
Back to Top
This trial is encouraging for patients with inactive thyroid eye disease, who have, up to now, looked at surgical rehabilitation as the only therapeutic choice.
The trial involved patients with long duration of disease (more than 2 years) and with clinical activity score of less than 2. The trial had a positive result, and the primary outcome and benefit of teprotumumab in this population was present in respect to proptosis. To put in perspective, though, the likelihood of a good response and the amplitude of the result was somewhat inferior to the results noted in the early and active thyroid eye disease trials.
Reassuringly, the safety profile has been consistent with prior data, with the major points that need to be discussed upfront and monitored during therapy being hyperglycemia and hearing changes. As far as secondary outcome, there was an improvement in the quality of life functional scale, but not in the appearance scale, and the analysis of diplopia did not indicate a benefit for teprotumumab in this population. Given the structure of the trial, it is not possible to conclude whether a different trial would not indicate different results in these areas.
Hopefully additional data will accumulate in inactive thyroid eye disease populations, confirming these results as well as allowing for identification of patients most likely to experience the positive outcome reported here.
Collapse
Click Here to Manage Email Alerts