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Teprotumumab for Thyroid Eye Disease
Treatment decisions consider benefits, risks, cost, and logistics. Cheryl Guttman Krader reports
Intravenous teprotumumab (TEPEZZA®, Horizon Therapeutics) can improve signs and symptoms related to thyroid eye disease (TED) in most patients. However, it is not a miracle drug—it is very expensive, and there are a variety of logistical issues accompanying its use, according to oculoplastic surgeon Anne Barmettler MD.
Dr Barmettler reviewed topline results from a clinical trial that supported US FDA approval of teprotumumab for the treatment of TED and shared her insights gleaned from some oculoplastic surgery colleagues who had clinical experience with the drug.
“There has been a lot of excitement about teprotumumab among physicians and patients. However, it is important for patients to understand it involves a six-month commitment involving eight infusions and is not a one-time treatment,” Dr Barmettler said.
“In addition, not all patients respond to teprotumumab, some patients still need surgery, and relapses occur. Furthermore, all patients should be monitored for side effects. A course of teprotumumab costs $300,000, and the need to obtain prior authorisation leads to a delay in starting treatment.”
Based on these considerations, Dr Barmettler said she mostly uses teprotumumab for treating TED in patients with very active, clinically severe disease. She noted she is also using it for treating TED-related optic neuropathy—although research is needed to determine the role of teprotumumab for that purpose and for treating chronic, non-inflammatory TED.
“Once I discuss the logistics of teprotumumab with patients, it may not be so appealing. Most patients who ask about teprotumumab do not choose it if they do not have severe TED.”
Rachel K Sobel MD does not offer teprotumumab to most patients she sees for TED.
“I think the TED needs to be quite severe, and this approach is being confirmed by some of the requirements set by insurers. The stakes are higher with teprotumumab. Therefore, we need to be good stewards of our healthcare system and offer teprotumumab only to patients who we think are really in need and will benefit.”
WHAT PHYSICIANS AND PATIENTS CAN EXPECT Premarketing clinical trials of teprotumumab were conducted in patients with recent-onset active TED. Reviewing outcomes for the teprotumumab group in one double-blind, randomised, placebo-controlled clinical triali, Dr Barmettler noted 83% of patients achieved the primary endpoint (≥2 mm reduction in proptosis from baseline at week 24), 68% of those with diplopia achieved an improvement of ≥1 grade, and 59% of patients achieved a Clinical Activity Score of 0 to 1 (a composite score ranging from 0 to 7 that assesses inflammation, oedema, redness, and pain).
“However, it is important to note the response rates were not 100%. Furthermore, only 53% of proptosis responders maintained the improvement at 1.5 years, and proptosis generally improves more than lid retraction or inflammation,” Dr Barmettler said.
Side effects during the study included increased blood glucose in 10% of patients, of whom two-thirds had pre-existing diabetes or impaired glucose tolerance. Other side effects included hearing loss or hearing changes (such as muffled hearing) in 10% of patients, inflammatory bowel (IBD) exacerbation, and amenorrhea.
Dr Barmettler said the oculoplastic surgeons she polled felt the side effect profile of teprotumumab was better than immunosuppressant agents such as mycophenolate mofetil used to treat TED. Less encouraging, however, are reports that hearing-related side effects are occurring at rates of 14% to 50% and are not always reversible. In addition, more reports of IBD exacerbation are emerging, and the blood glucose increases can be very high.
“We have had patients requiring hospitalisation for a blood glucose in the 700s,” Dr Barmettler said.
CLINICAL CONSIDERATIONS Because of its associated risks, some clinicians are checking for hyperglycaemia prior to starting teprotumumab. Experts recommend monitoring for elevated blood glucose during treatment. In addition, some clinicians are testing hearing prior to starting treatment in patients with existing hearing loss while other clinicians are sending all patients for an audiology evaluation.
Monitoring for IBD flares is also recommended in patients with pre-existing disease. Because of its mechanism of action— insulin-like growth factor 1 receptor inhibition—teprotumumab can affect growth in children and cause foetal harm. Therefore, it should not be used in children, and it is recommended women use contraception while receiving teprotumumab, including for six months after the last infusion.
Logistical issues in the US also relate to the prior authorisation process that is extensive and very time consuming for the clinical and business staff. Compounding the complexity, approval criteria vary among insurers. In addition, the authorisation process may need to start again if there is a desire to change the physical site (hospital, outpatient infusion centre, home) where the patient is receiving the infusion.
The study was presented at the AAO 2021 conference in New Orleans, Louisiana, USA.
i Douglas RS, et al., New England Journal of Medicine. 2020; 382: 341–352.
