Teprotumumab: TED treatment shows benefits for patients

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The FDA approved teprotumumab-trbw (Tepezza; Amgen) in 2020 for treating thyroid eye disease (TED) following promising results from clinical trials. Although thousands of patients have received the monoclonal antibody, which targets the insulin-like growth factor 1 receptor, its use in clinical practice remains relatively new, and long-term real-world data remain limited.

The results of 2 recent real-world studies show encouraging outcomes and indicate that the drug is performing well for a high percentage of patients with TED regarding the need for retreatments and intervention with orbital decompression.

Retreatment rates with teprotumumab

Shoaib Ugradar, MD, and colleagues conducted a multicenter, retrospective study¹ to determine the retreatment rate in patients who underwent a full course of teprotumumab to treat TED and to identify the factors that drove the need for retreatment. Ugradar is from the Department of Orbital and Ophthalmic Plastic Surgery, Private Practice, Beverly Hills, California.

Teprotumumab was found to cause significant decreases in diplopia, proptosis, and inflammation in phase 2 and 3 clinical trials.2,3 When the results of the 2 studies were pooled, at 24 weeks, 77% of patients treated with teprotumumab saw significant decreases in proptosis compared with 15% treated with placebo.¹ In patients evaluated at 51 weeks, 67% had significantly reduced proptosis, and 69% of those with diplopia still had a diplopia response.^3,4

The OPTIC-X extension study4 of the phase 2 OPTIC trial, which evaluated the durability of teprotumumab, showed that 29% of patients who responded to teprotumumab had a flare-up of proptosis at 51 weeks. Patients in the extension study had data available at 1 year following the first treatment. The investigators collected the following data from the patient charts: age, gender, months since the TED diagnosis, smoking status, and previous treatments.

The clinical activity score (CAS), proptosis, and the Gorman diplopia score were reviewed at baseline, at the end of the first course, and at baseline for the second course in those treated with teprotumumab. The main outcomes were the retreatment rate and the drivers of retreatment, the authors recounted. The study included 119 patients from 3 US centers in Beverly Hills; Boston, Massachusetts; and Miami, Florida.

“The overall retreatment rate was 24%; that is, 29 of the 119 patients, with no significant difference among the 3 sites,” Upgradar and colleagues reported. “No differences were found between the patients who required retreatment and those who did not in proptosis (P = .07), diplopia score (P = .4), or duration of TED (P = .4). Of the re-treated patients, “82% had had a significant proptosis response after the first treatment course, while 68% of patients had a clinically significant proptosis response” in the group that was not re-treated (P = .16), according to the authors.

The use of other treatments before the first teprotumumab infusion and the baseline thyroid dysfunction did not differ significantly between the retreated group and the group that was not re-treated (P = .06 and P = .09, respectively). In the teprotumumab-treated patients, the mean ± SD differences between the end of the first treatment and at baseline before the second treatment were 2 ± 2 for the CAS, 2 ± 4 mm for proptosis, and 1 ± 1 for diplopia.

Patient age was the only factor that correlated significantly with the need for retreatment (P < .05). The patients who were re-treated were 7 years older than their counterparts who were not (age, 60 vs 53 years; P < .05), the authors reported.

In commenting on the findings, the authors explained that the “rate of retreatment is an indirect measure of the durability of the effect of teprotumumab on TED. However, given the growing body of evidence that suggests TED is a chronic disease, it is likely that a group of patients receiving teprotumumab will require further treatment. Our study reveals that this group of patients is likely to be older. Having identified a retreatment rate and a risk factor, it may be possible to better inform patients prior to initiating treatment.”

“Teprotumumab has transformed the TED treatment landscape as a targeted therapy that addresses many of the serious and often debilitating symptoms of TED and has made a positive difference for many of my patients,” Ugradar said. “Our study builds upon the promising findings of prior clinical trials with teprotumumab and further underscores its potential as a long-term treatment option” for patients with TED.

Orbital decompression after teprotumumab

A study of the need for orbital decompression after treatment with teprotumumab found that the number of surgeries declined,⁵ according to lead author Nicole Topilow, MD; and senior author Don O. Kikkawa, MD, of the Division of Oculofacial Plastic and Reconstructive Surgery, UC San Diego Health Viterbi Family Department of Ophthalmology, and Shiley Eye Institute in La Jolla, California.

Orbital decompression surgery was a primary treatment for reducing thyroid-related proptosis before the availability of teprotumumab. The procedure is a safe and effective method of treating proptosis,⁶ but the downsides are the lengthy recovery periods and possible postoperative adverse effects (ie, new or worsened diplopia and other complications).^7-11 Other treatments, such as intravenous steroids, radiation, and off-label biologic therapy, are available, but their effectiveness varies.^12,13

Topilow and colleagues conducted a retrospective chart review to identify changes in the rate of surgical orbital decompression procedures performed since teprotumumab became available, to determine how many patients underwent decompression surgery after treatment with teprotumumab, and to identify which factors predict the patients with moderate to severe TED who will undergo decompression surgery after treatment with teprotumumab, they explained. The main outcome measure was whether patients underwent bony orbital decompression surgery following treatment of TED.

Topilow and colleagues used the Epic SlicerDicer program to analyze recent trends in the overall number of patients with TED who had been examined in the Oculoplastic Surgery Department and to analyze the usage trends of Current Procedural Terminology (CPT) codes 67445 (lateral orbitotomy with bone removal for decompression) and 67414 (orbitotomy with removal of bone for decompression).

“The search demonstrated stable usage of CPT codes 67445 and 67414 from 2016 to 2019, followed by a significant decrease from 2020 to 2023, over a background of increasing numbers of [patients with TED] evaluated in clinic,” the authors explained. “Following teprotumumab therapy, 25% of patients and 18% of orbits underwent bony decompression. Surgically decompressed patients had higher [preteprotumumab] and postteprotumumab exophthalmometry measurements compared with patients who did not undergo bony decompression.”

The average time to decompression following the conclusion or cessation of teprotumumab therapy was 12.6 months. “While the number of TED patients treated at 1 tertiary care center has risen over recent years, the number of orbital decompression surgeries has declined,” the investigators wrote. “Orbital decompression, however, is still needed in select patients after treatment with teprotumumab.”

They also pointed out that further studies with more patients will confirm the applicability of these findings to determine how treatment with teprotumumab affects rates of eyelid surgeries and to examine which patients with TED, if any, may do better with 1 treatment modality.

“The introduction of teprotumumab has had a great impact on our treatment of [patients with TED], playing a key role in the reduction of orbital decompression performed at our center since its availability,” Kikkawa said. “Our findings suggest teprotumumab is a preferred, less invasive treatment for many patients and likely reduces the need for orbital decompression.”

References:

1. Ugradar S, Parunakian E, Malkhasyan E, et al. The rate of re-treatment in patients treated with teprotumumab: a multicenter study of 119 patients with 1 year of follow up. Ophthalmology. Published online July 19, 2024. doi:10.1016/j.ophtha.2024.07.018

2. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761. doi:10.1056/NEJMoa1614949

3. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341-352. doi:10.1056/NEJMoa1910434

4. Kahaly GJ, Douglas RS, Holt RJ, Sile S, Smith TJ. Teprotumumab for patients with active thyroid eye disease: a pooled data analysis, subgroup analyses, and off-treatment follow-up results from two randomised, double-masked, placebo-controlled, multicentre trials. Lancet Diabetes Endocrinol. 2021;9(6):360-372. doi:10.1016/S2213-8587(21)00056-5

5. Topilow NJ, Penteado RC, Ting M, et al. Orbital decompression following treatment with teprotumumab for thyroid eye disease. Can J Ophthalmol. Published online July 24, 2024. doi:10.1016/j.jcjo.2024.06.003

6. Ediriwickrema LS, Korn BS, Kikkawa DO. Orbital decompression for thyroid-related orbitopathy during the quiescent phase. Ophthalmic Plast Reconstr Surg. 2018;34(4S suppl 1):S90-S97. doi:10.1097/IOP.0000000000001119

7. Jefferis JM, Jones RK, Currie ZI, Tan JH, Salvi SM. Orbital decompression for thyroid eye disease: methods, outcomes, and complications. Eye (Lond). 2018;32(3):626-636. doi:10.1038/eye.2017.260

8. Cheng AMS, Wei YH, Liao SL. Strategies in surgical decompression for thyroid eye disease. Oxid Med Cell Longev. 2020;2020:3537675. doi:10.1155/2020/3537675

9. Graham SM, Brown CL, Carter KD, Song A, Nerad JA. Medial and lateral orbital wall surgery for balanced decompression in thyroid eye disease. Laryngoscope. 2003;113(7):1206-1209. doi:10.1097/00005537-200307000-00017

10. Sellari-Franceschini S, Berrettini S, Santoro A, et al. Orbital decompression in Graves’ ophthalmopathy by medial and lateral wall removal. Otolaryngol Head Neck Surg. 2005;133(2):185-189. doi:10.1016/j.otohns.2005.02.006

11. European Group on Graves’ Orbitopathy (EUGOGO); Mourits MP, Bijl H, Altea MA, et al. Outcome of orbital decompression for disfiguring proptosis in patients with Graves’ orbitopathy using various surgical procedures. Br J Ophthalmol. 2009;93(11):1518-1523. doi:10.1136/bjo.2008.149302

12. Taylor PN, Zhang L, Lee RWJ, et al. New insights into the pathogenesis and nonsurgical management of Graves orbitopathy. Nat Rev Endocrinol. 2020;16(2):104-116. doi:10.1038/s41574-019-0305-4

13. Khong JJ, McNab A. Medical treatment in thyroid eye disease in 2020. Br J Ophthalmol. 2021;105(3):299-305. doi:10.1136/bjophthalmol-2020-316051