Teprotumumab, tocilizumab improve thyroid eye disease symptoms within 24 weeks
Click Here to Manage Email Alerts
Key takeaways:
- Adults with thyroid eye disease had reductions in proptosis and diplopia at 24 weeks with teprotumumab or tocilizumab.
- The improvements were similar regardless of whether adults previously received steroids.
Both teprotumumab and tocilizumab reduce inflammation and thyroid eye disease severity, including among adults who were nonresponders to steroid treatment, according to findings published in Thyroid.
“Medical therapy with teprotumumab and tocilizumab can be considered in patients that have failed steroid therapy for thyroid eye disease,” Marius N. Stan, MD, consultant in endocrinology and chair of the thyroid care group at Mayo Clinic in Rochester, Minnesota, and David Toro-Tobon, MD, assistant professor of medicine in the division of endocrinology, diabetes and metabolism at Mayo Clinic, told Healio. “Teprotumumab particularly shows a substantial reduction in proptosis and diplopia, while the tocilizumab subgroup demonstrates meaningful improvement in disease activity and severity linked to reduced inflammatory features, although its effect on proptosis is less pronounced. The number of treated patients is small, particularly for tocilizumab, therefore more data will be needed to verify our findings.”
Stan, Toro-Tobon and colleagues conducted a retrospective single-center study of 37 adults treated for moderate or severe thyroid eye disease with teprotumumab-trbw (Tepezza, Horizon Therapeutics) or tocilizumab (Actemra, Genentech) from 2018 to 2022 (mean age, 57 years; 72.9% women; 89.1% white). Adults were defined as having steroid-resistant thyroid eye disease if they previously failed treatment with 4 g dose of IV methylprednisolone or a 6-week course of oral prednisone. All other participants were considered to be steroid naive. Proptosis response was defined as a 2 mm or greater reduction in proptosis with no increase in the contralateral eye. Median excess proptosis was proptosis above normal for the person’s gender and race. Thyroid eye disease severity was based on the European Group on Graves’ orbitopathy. Adults were evaluated at baseline, 12, 24 and 52 weeks. All data were collected from electronic medical records.
Both agents reduce proptosis, diplopia
Of the study group, 13 were steroid resistant and received teprotumumab, 18 were steroid naive and received teprotumumab, and eight were steroid resistant and received tocilizumab.
Among the steroid-resistant teprotumumab group, all participants had diplopia and a median excess proptosis of 4.5 mm at baseline. At 24 weeks, 83.3% of the group had a proptosis reduction of at least 2 mm and median excess proptosis dropped to 2 mm. The presence of diplopia declined to 54.5%, and 58.3% improved to mild thyroid eye disease severity.
The steroid-naive teprotumumab group had a median excess proptosis of 5 mm at baseline and 72.2% had diplopia. Of the group, 78.6% had a proptosis reduction of at least 2 mm at 24 weeks and the prevalence of diplopia dropped to 57.1%. Median excess proptosis declined to 2 mm, and 42.9% improved to mild thyroid eye disease severity.
The tocilizumab group had a median excess proptosis of 2 mm at baseline and 66.7% had diplopia. At week 24, 50% of the group had a proptosis reduction of at least 2 mm. Median excess proptosis did not clinically change during the study. The prevalence of diplopia decreased by 16.7%, and 75% of the group had an improvement to mild disease severity.
Trends toward worse severity and increased diplopia were observed from week 24 to week 52 in all three groups, but outcomes generally remained improved at 52 weeks compared with baseline.
“Thyroid eye disease commonly presents with an active phase followed by a quiescent phase,” Stan and Toro-Tobon said. “Reactivations can occur in a subset of patients regardless of treatment. As neither therapy targets the underlying autoimmune mechanism, even those with strong initial responses might face future flares. Our study found reactivations in 15% of tocilizumab and 30% of teprotumumab patients. Yet, more research is necessary to identify predictors of post-therapy reactivation, define response duration and determine the need for retreatment in specific cases.”
Adverse events common with teprotumumab
Adverse events were reported by 76.9% of steroid-resistant adults receiving teprotumumab, 72.2% of steroid-naive participants receiving teprotumumab, and no one in the tocilizumab group. Otic changes were the most common adverse events in the steroid-resistant adults, whereas those who were steroid naive reported muscle spasms as the most common adverse event. Two serious adverse events were reported, with one being a retropharyngeal abscess complicated by severe sepsis due to Escherichia coli, and the second being acute pancreatitis complicated by peripancreatic necrosis and abscess. Both adults discontinued teprotumumab.
“Future research should focus on validating these results in other centers,” Stan and Toro-Tobon said. “In parallel, we should design and implement a standardized screening and monitoring protocol for early detection and management of possible adverse events arising from these drugs, particularly teprotumumab. The duration of therapy and identification of biomarkers that would predict disease relapse should be another focus of upcoming research. Lastly, further work toward designing drugs that more effectively alter the root cause of this autoimmune entity should continue.”
For more information:
Marius N. Stan, MD, can be reached at stan.marius@mayo.edu
David Toro-Tobon, MD, can be reached at torotobon.david@mayo.edu
Perspective
Back to Top
The study by Toro-Tobon and colleagues is a retrospective case-control study investigating outcomes and safety in patients with moderate to severe steroid-resistant thyroid eye disease treated with teprotumumab or tocilizumab compared with steroid-naive patients, up to 52 weeks after therapy initiation. The efficacy of teprotumumab in the 13 steroid-resistant patients was the same as in the 18 steroid-naive patients, while tocilizumab showed some efficacy in 6 steroid-resistant patients.
This study is important for two reasons. First, it is the first study to report on teprotumumab effects in steroid-resistant thyroid eye disease patients. The fact that efficacy and side effects were similar in that group compared with the steroid-naive patients receiving teprotumumab (the only population studied in randomized controlled trials) is encouraging. Secondly, the study confirms the efficacy of tocilizumab in steroid-resistant patients, which has only been shown so far in data from a single center in Spain.
A few limitations need to be considered. The study is very small, limiting interpretation of outcomes and conclusions. The lack of a steroid-naïve tocilizumab control does not yield new insights into the efficacy of tocilizumab in the less heavily treated thyroid eye disease population. A significant proportion of patients were not available for the 52 week follow-up. The design was retrospective and there was therefore bias in the selection and availability of treatment. Finally, there was selection bias in the tocilizumab group, as most patients had to pay out of pocket due to lack of FDA approval. Despite these limitations, the findings are interesting and encouraging regarding efficacy of these agents in steroid-resistant thyroid eye disease, and invite further confirmatory research in larger groups, ideally in the setting of randomized controlled trials.
Collapse
Read more about
Click Here to Manage Email Alerts