If you see patients with Thyroid Eye Disease, or T-E-D, you may be considering treating them with TEPEZZA, the first
and
only FDA-approved treatment option for T-E-D regardless of disease duration or activity.
One of the adverse events that occurred in TEPEZZA clinical trials was hearing impairment.
Please stay tuned for Important Safety Information about TEPEZZA at the end of this video.
First, let us look more closely at the data on hearing from the clinical trials.
TEPEZZA has a proven efficacy with a demonstrated safety and tolerability profile.
TEPEZZA has been studied in three placebo-controlled clinical trials in active and chronic T-E-D.
Before we get started, please note that baseline hearing tests were not conducted for these trials.
Some patients taking TEPEZZA in clinical trials reported a range of hearing-related side effects, including hearing
loss, deafness, including sensorineural deafness, eustachian tube dysfunction, hyperacusis, hypoacusis, autophony,
and
tinnitus.
In the Phase 2 and 3 trials, approximately 10% (8 of 84) patients treated with TEPEZZA reported experiencing hearing
impairment versus none of the 86 patients treated with placebo.
In the 8 TEPEZZA-treated patients, hearing events resolved in 6 and improved in 1 patient, during the 24-week
double-masked period.
In the Phase 4 trial, approximately 22% (or 9 of 41) patients treated with TEPEZZA reported experiencing hearing
impairment versus 10% (2 of 20) patients treated with placebo.
In the TEPEZZA-treated patients, 3 out of 9 cases of hearing impairment resolved or were resolving during the
follow-up
period. Note that this follow-up period was only 30 days.
One patient discontinued TEPEZZA in the open-label treatment period due to left ear conductive hearing loss, later
found
to be linked to a congenital anomaly, discovered prior to the completion of the double-masked period.
Most hearing events were mild or moderate, and a majority of the patients completed treatment.
A separate prospective observational study identified potential risk factors related to hearing impairment in 52
patients who completed a full course of TEPEZZA.
Audiometry showed that approximately 38% (20 of 52) of these patients had hearing dysfunction at baseline. They found
that patients reporting hearing impairment with TEPEZZA tended to be older and had higher baseline Clinical Activity
Score (or C-A-S), along with preexisting hearing issues as assessed at baseline.
Please note that, since this data was not derived from a controlled clinical study, no conclusions of statistical or
clinical significance can be drawn.
To better understand how TEPEZZA may impact the auditory system, let us look at the role of IGF-1R in T-E-D and how
it
is targeted by TEPEZZA.
IGF-1R is involved in the pathogenesis of Thyroid Eye Disease because it is overexpressed in T-E-D orbital
fibroblasts.
TEPEZZA is designed to bind to IGF-1R and block its activation and signaling.
By targeting IGF-1R in orbital fibroblasts, TEPEZZA reduces inflammation and prevents muscle and fat tissue
remodeling
and expansion behind the eye.
Though the exact mechanism of hearing impairment with TEPEZZA is unknown, IGF-1 signaling provides a plausible link.
Among other signaling pathways in various extraorbital tissues, IGF-1R and IGF-1 are also linked to the maintenance
of
hearing function.
IGF-1 is involved in the maintenance of the number of inner and outer hair cells, it potentially has a protective and
proliferative effect on the cochlea, and regulates the timing of sensory cell differentiation.
Sensorineural hearing loss can occur in patients with IGF-1 deficiency.
Although there is more to learn about the role of IGF-1 signaling in hearing, it may provide a link between hearing
impairment and TEPEZZA.
Studies have suggested that patients with Graves’ disease can experience a decrease in hearing ability, especially at
higher frequencies.
The FDA-approved label for TEPEZZA states to evaluate patients’ hearing before, during, and after treatment with
TEPEZZA.
It is important to have a conversation with your patients prior to treatment with TEPEZZA to set expectations and
ensure
you have a monitoring plan in place.
There is a risk of hearing impairment with TEPEZZA. I think it's important to note that it doesn't always mean
hearing
loss or sensorineural hearing loss or deafness, other side effects such as tinnitus or ringing in the ears or
muffling
in the ears, which can sound like somebody's underwater.
If you were thinking about starting your patient on TEPEZZA, I would recommend establishing a protocol for monitoring
for hearing impairment. I would first counsel the patient about potential risks, benefits associated with TEPEZZA,
and
hearing-related side effects. I would then also ensure that patients have a protocol for baseline audiology testing,
audiology testing after the fourth infusion, and again, repeat audiology testing at the end of treatment and I
gather
all the data and review it together with the patient.
One thing that I've done in my practice is that I have established good rapport with a few local audiologists. In my
experience, patients that have hearing-related side effects do tend to have improvement or resolution of those
symptoms
after treatment is completed.
One of the things I’m doing is, I’m getting a baseline audiogram and through the course of the TEPEZZA infusions, I’d
meet with the patient in subsequent visits, and I do always ask about hearing changes and if they have noticed any
change in their hearing. If they do, we do get a confirmatory audiogram.
I’m at an academic hospital, so I’m lucky in that I have all specialties under one roof. So, I commonly will do
audiology consults now for thyroid eye disease patients. I have ear, nose, and throat colleagues around the corner
that
I can send patients to, to get formal evaluations of their hearing should we notice that there is a deficit, and to
make
sure there’s no other problems which could be contributing to their hearing changes.
I think it's really important to counsel patients on hearing.
As my practice has evolved over the five years, I really find that it's best for patients that they get into the
formal audiology center. And the reason for that is if a patient has noticed any changes in their hearing, now we
have some sort of quantitative factor where I can compare what their hearing was.
In addition, I find that it's really helpful for patients because when they've gone in and had a formal hearing
study, now they're already established at a location. So, if there's issues now, they are not panicked about where
to go, but they know to go back to the same facility again.
INDICATION
TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in
approximately
4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity.
Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea,
headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an
infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with
an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower
infusion rate.
Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel
disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider
discontinuation of TEPEZZA.
Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In
clinical
trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced
hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary.
Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to
monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under
appropriate glycemic control before and while receiving TEPEZZA.
Hearing Impairment Including Hearing Loss: TEPEZZA may cause severe hearing impairment including hearing loss,
which in some cases may be permanent. Assess patients’ hearing before, during, and after treatment with TEPEZZA
and consider the benefit-risk of treatment with patients.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders.
Please see Full Prescribing Information or visit TEPEZZAhcp.com for more information.
