Even Inactive Thyroid Eye Disease Adversely Impacts Patients
Ocular signs and symptoms of thyroid eye disease (TED) often persist beyond the active phase of the condition, with many patients continuing to experience mental health issues and diminished quality of life, new research suggests.
The autoimmune condition TED involves orbital inflammation with subsequent proptosis (eye bulging), diplopia, corneal exposure, vision changes, and potential blindness. The initial acute progressive phase of active inflammation lasts between 1 and 3 years. Inflammation then typically subsides, but patients can still experience chronic sequelae including ocular pain and discomfort, vision disturbance, and facial disfigurement.
Findings from a cross-sectional survey comparing about 300 patients with active or inactive TED were presented May 29 at the American Association of Clinical Endocrinology (AACE) Virtual Annual Meeting 2021 by Lissa Padnick-Silver, PhD, senior manager of medical affairs at Horizon Therapeutics, Deerfield, Illinois.
“Chronic TED is generally thought of as inactive and stable, but the persistence of ocular signs/symptoms, mental health issues, and long-term impairment of patient quality of life make TED seem anything but ‘inactive,’ especially to the patient,” Padnick-Silver said.
Horizon makes the monoclonal antibody teprotumumab (Tepezza), which was approved by the US Food and Drug Administration in January 2020 for the treatment of adults with TED. The survey was conducted in 2018 prior to the drug’s approval.
Asked to comment, session moderator Jad G. Sfeir, MD, of the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “Many of us assume that once the eye disease is inactive it shouldn’t be causing any trouble in the background anymore. However, we see now that there is a good proportion [of patients] who continue to have depression and other mental health and psychosocial effects that will impact them. This type of study will enlighten physicians definitely to ask more about these with the hope that we can offer some help to these patients.”
However, Sfeir noted that the study did not provide any guidance on how to treat the problem. “The biggest issue, of course, is what to do to help, and whether the new drug that has been on the market for a little over a year now will make a difference in terms of quality of life, and whether it will have any impact even after the disease goes inactive and you stop the medication. Will that change the quality of life in the inactive disease that was treated? We just need to wait for long-term data to be able to answer this question.”
Sfeir also cautioned about over-interpreting the data, particularly those concerning rates of reported anxiety and depression, given the cross-sectional nature of the study.
Mental Health Impact of Inactive TED Found to Be High
The study was a retrospective analysis of medical record data provided by 181 US physicians — endocrinologists and ophthalmologists — for a total of 714 patients who had moderate-to-severe TED. Of those, 281 patients (39%) had active TED defined as a clinical activity score (CAS) of 3 or greater, and 307 patients (43%) had inactive TED, defined as a CAS of 0 or 1. The rest, with CAS 2, were not included in the analysis.
About two thirds of both groups were women, with a mean age of around 50 years. The group with inactive TED was diagnosed at a slightly younger age (43.8 vs 46.1 years; P = .031). At the time of the survey, the proportions with severe TED were 5% with inactive disease versus 25% with active TED (P < .001). The mean CAS was 0.5 for those with inactive TED versus 4.1 for active TED (P < .001). There were no significant differences in thyroid status, smoking status, or TED duration.
Ocular dryness/grittiness was the most common ocular symptom in both groups, reported by 77% with inactive TED and 92% with active TED.
For those with inactive TED, the next most commonly listed ocular symptoms were proptosis in 56%, excessive tearing in 43%, and soft-tissue edema in 42%.
That list contrasts somewhat from the active TED group, in whom the next three most common symptoms were soft-tissue edema in 92%, conjunctival redness in 90%, and proptosis in 78%. Decreased vision was reported by 24% with inactive TED, compared to 63% with active TED.
Mental health issues were reported by 37% with active TED and 36% with inactive TED, not significantly different from each other but significantly higher than the 19% seen in the general US adult population, as reported by the National Institute of Mental Health in 2017, Padnick-Silver said.
Specifically, anxiety was reported in 28% with active TED and 26% with inactive TED, compared with 19% in the general US population. Depression was reported in 19% and 17% versus 7%, respectively.
Regarding the mental health statistics, Sfeir said that although it’s somewhat surprising that more than a third with inactive disease reported having anxiety and/or depression, at the same time, “it’s a cross-sectional survey, so hard to know what it means. Their background may be different. Some may have had active disease before and some not. Also, we don’t know the status of their thyroid treatment or whether they have other autoimmune diseases. We need a bit more information to make good sense of these data.”
Quality of Life Also Affected
Physicians also rated the impact of TED on the patients’ quality of life using a seven-point Likert scale, with one being not at all impaired and seven being extremely impaired.
Overall, those with inactive TED were given a score of 3.6, and those with active TED, 4.7. For all the subscales — work/school, social, daily activities, driving, and psychological well-being — all scores were 3.1 or greater for inactive TED and 4.1 or greater for active TED. Psychological well-being was most affected in the inactive TED and active TED groups (3.6 and 4.6).
“These findings agree with a previous study of mostly moderate-to-severe TED patients, which showed that some psychologically adapt to appearance changes and functional limitations associated with TED,” Padnick-Silver commented.
The 281 patients with inactive TED were divided into 166 with short-term TED (duration 3 years or less) and 115 with long-term TED (more than 3 years). Reported TED signs and symptoms were similar between the two groups, except for ocular dryness/grittiness, which was more prevalent in the long-term TED group (85% vs 72%; P = .009).
Quality of life scores were also similar between the groups (3.4 vs 3.7; P = .073), and the prevalence of mental health issues — anxiety and/or depression — was identical, at 36% for both.
During the question-and-answer period, Sfeir asked Padnick-Silver whether there were plans to repeat the study now that teprotumumab, the first disease-modifying treatment for TED, is available.
She replied, “It would be a wonderful thing; it’s certainly in talks. There are no active plans to do that, but it is definitely something we’re interested in.”
The study was funded by Horizon. Padnick-Silver is a Horizon employee and stockholder. Sfeir has reported no relevant financial relationships.
AACE Virtual Annual Meeting 2021. Presented May 29, 2021.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.
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