Teprotumumab in thyroid eye disease: wonder drug or great divider?

in European Thyroid Journal
Authors:
Petros Perros Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK

Search for other papers by Petros Perros in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0001-7320-5574
and
Laszlo Hegedüs Department of Endocrinology Odense University Hospital, Odense, Denmark

Search for other papers by Laszlo Hegedüs in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-9691-7619

Correspondence should be addressed to P Perros: petros.perros@ncl.ac.uk
Open access

Sign up for journal news

Progress in the management of thyroid eye disease (TED) has been slow for many decades. The recent introduction of teprotumumab (TEP) in the therapeutic arena for TED has had a major impact in view of its efficacy, particularly with respect to its ability to reduce proptosis. However, the high cost of TEP, limited availability to patients outside the USA, and the lack of data on cost-effectiveness are significant barriers to improving the care of patients with TED globally. Recent guidance from authoritative professional organisations deliver different perspectives on the role of TEP in the routine management of patients with TED, underscoring the complexities of interpreting the evidence. The advance that TEP undoubtedly represents in managing TED effectively has highlighted inequities faced by patients and uncertainties about appropriate metrics of efficacy. Professional organisations have an important role addressing these problems. Future studies need to focus on optimising the measurement of outcomes and on assessing cost-effectiveness.

Abstract

Progress in the management of thyroid eye disease (TED) has been slow for many decades. The recent introduction of teprotumumab (TEP) in the therapeutic arena for TED has had a major impact in view of its efficacy, particularly with respect to its ability to reduce proptosis. However, the high cost of TEP, limited availability to patients outside the USA, and the lack of data on cost-effectiveness are significant barriers to improving the care of patients with TED globally. Recent guidance from authoritative professional organisations deliver different perspectives on the role of TEP in the routine management of patients with TED, underscoring the complexities of interpreting the evidence. The advance that TEP undoubtedly represents in managing TED effectively has highlighted inequities faced by patients and uncertainties about appropriate metrics of efficacy. Professional organisations have an important role addressing these problems. Future studies need to focus on optimising the measurement of outcomes and on assessing cost-effectiveness.

Introduction

Thyroid eye disease (TED) is an autoimmune condition associated with Graves’ disease affecting approximately 0.1% of the population (1, 2). TED can result in altered appearance and other significant symptoms, impacts negatively on patients’ quality of life (QOL) (3, 4), and is associated with poor socioeconomic outcomes (3, 5, 6) and excess mortality (7, 8). The traditional standard of care for active, moderate-to-severe TED is systemic glucocorticoid, which, however, has limited efficacy, with overall response rates of 23–53% (9), little impact on proptosis, and a relapse rate of about 20%, although disease inactivation is reported in up to 80% of cases (10).

The purpose of this commentary is to appraise the current role of teprotumumab (TEP) in the context of recently published guidance and highlight the considerable challenges ahead, including ethical considerations.

Efficacy of TEP

TEP is a monoclonal antibody which blocks the insulin-like growth factor-1 receptor (IGF1R). Cross-talk between the IGF1R and thyroid-stimulating hormone receptor on orbital cells is thought to be of major importance in the pathogenesis of TED (11, 12, 13), and disruption of this process appears to be a key mechanism of action of TEP (14). TEP was licenced in the USA for the treatment of TED in January 2020. The evidence for efficacy derives largely from two randomised placebo-controlled trials (RCTs) of similar design (15, 16), additional data from the open-label phase of the RCTs (17, 18), and small case series and case reports (19, 20, 21, 22, 23, 24, 25).

The RCTs targeted patients with moderate-to-severe TED with a clinical activity score (CAS) >4/7 and a disease duration <9 months who had either no previous medical treatment for TED or only oral glucocorticoids <1 g cumulative dose. TEP seems to be a highly efficacious drug for active, moderate-to-severe TED with overall response rates of 74% (18). In addition, proptosis reduced by an average of 2.8 mm, the disease was inactivated in 59–69% of patients, and diplopia improved in 70% of patients (15, 16, 18). TEP is the only medical treatment shown convincingly to reduce proptosis to a degree comparable with surgical orbital decompression in TED. According to Food and Drug Administration (FDA) documentation, relapses in proptosis after completion of treatment occur in 37% of patients (https://www.fda.gov/media/133429/download), which may be responsive to further treatment with TEP (17, 18). The high-quality evidence for TEP demanded by the FDA and achieved by the two RCTs (15, 16) has not been fulfilled for glucocorticoids or for a number of other alternative treatments that became standard clinical practice before stringent licencing measures were adopted.

Data on prevention of surgical procedures are an important metric of efficacy; however, they are hard to come by for any medical treatment for TED. Appraisal of prevention of surgical interventions requires prospective studies of sufficiently long duration with pre-defined indications for each surgical procedure. The available data on prevention of surgical treatment for TEP are scanty and difficult to interpret. Direct comparisons between glucocorticoids and TEP do not exist, and using historical data is subject to numerous potential biases; however, the superiority of TEP would seem to be beyond doubt. It is also notable that the FDA criteria imposed for efficacy differed to the prevailing wisdom among experts, which generally included a ‘composite index’ among primary end points (improvement in at least two parameters such as palpebral aperture and exophthalmos, diplopia, CAS, and QOL) (26). A significant knowledge gap has therefore been exposed regarding the choice of the most appropriate and clinically relevant end points. Questions that remain unanswered include the following: ‘is the composite score clinically meaningful?’ (27), ‘is the grading of diplopia by the Gorman score (28) fit for purpose?’ and ‘given that there are two validated disease-specific quality of life questionnaires available (29, 30) is one better than the other?’

An RCT has commenced to determine the efficacy of TEP in patients with chronic (inactive) TED and is expected to report at the end of 2023. In the meantime, TEP is being used for indications outside the inclusion criteria of the published RCTs (20, 21, 31, 32). The FDA approval does not stipulate specific indications for use of TEP other than ‘Tepezza is indicated in the treatment of Thyroid Eye Disease’ (https://www.fda.gov/media/133429/download), thus placing no barriers to its use for any patient with TED.

Safety of TEP

Adverse events during TEP treatment were reported by the RCTs in 80% of patients compared to 70% of placebo-treated patients, while serious adverse events occurred in 8% vs 1% in the placebo arm (18). Serious adverse effects with potentially life-changing outcomes following TEP administration include inflammatory bowel disease, hearing impairment, and encephalopathy (https://www.fda.gov/media/133429/download). Hearing loss in particular is concerning as it may be more frequent than reported in the RCTs and chronic (33, 34, 35). Outside RCTs, the FDA adverse events reporting system public dashboard currently contains data for up to the 31 December 2022 and lists 1879 reported adverse events, 213 of which are classified as serious, and there were 7 deaths; whether the latter were directly related to the drug is unclear as further details are not accessible on the FDA website (https://fis.fda.gov/sense/app/95239e26-e0be-42d9-a960-9a5f7f1c25ee/sheet/8eef7d83-7945-4091-b349-e5c41ed49f99/state/analysis).

A ‘real world’ report of 995 patients treated with TEP before July 2020 showed that 8% discontinued treatment because of drug-related adverse effects (https://ir.horizontherapeutics.com/node/19741/pdf), comparable to the serious adverse event rates reported by the RCTs (15, 16). Directly comparable data for intravenous glucocorticoids are not available, but the rate of serious adverse events for intravenous glucocorticoids has been reported to be 6.5%, the rate of all adverse events was 48% (no data for placebo), and the rate of mortality was 0.6% (10, 36). The safety profile of TEP therefore appears to be acceptable, although long-term experience is unavailable.

Cost considerations

The price of TEP for a course of treatment is approximately $360,000 for a 75 kg patient, more than 5000 times the cost of a course of intravenous glucocorticoids (9). If the 37% of patients who relapse (https://www.fda.gov/media/133429/download) are re-treated with TEP, the cost per patient would double, and in some patients (yet unclear what percentage) additional treatments including rehabilitative surgery may be required, resulting in further costs (which are expected to be less compared to glucocorticoid-treated patients, as fewer surgical decompressions are expected after TEP treatment). The above figures do not include the delivery of infusions, consultations, monitoring, or dispensing, which can be assumed to be similar to intravenous glucocorticoids.

The cost of TEP treatment is unprecedented in the field of TED, considering that the drug cost of the standard treatment (a 12-week course of intravenous methylprednisolone) is €70 in Europe ($172.08 in the USA) and the cost of a course of treatment with rituximab (another biologic used in TED) (37) is between €338 ($990) and €4308 ($19,636), depending on whether it is prescribed in Europe or USA and the dose regimen (9). Financial assistance is available for patients in the USA without insurance, but it is unclear what proportion of the US population who are eligible for TEP on clinical grounds have access to this treatment. Pricing outside the USA is likely to differ pending regulatory approval.

There are no data on the cost-effectiveness of TEP, no head-to-head comparisons with intravenous glucocorticoids (the current standard of care), or any other therapy, and no data on the optimal dose regimen for TEP. The merit of head-to-head comparisons with glucocorticoids and other established treatments in being able to appraise cost-effectiveness of TEP is crucial.

Ethical dimension

Clinicians who make decisions about costly treatments have an ethical responsibility to use resources efficiently. The question that follows is ‘whose responsibility is it to appraise cost-effectiveness of new health technologies?’ There are at least two reasons why that should not be left up to the individual physician. First, the process of evaluation is complex, specialised, and laborious, and few (if any) individual physicians have the skills and resources to perform such tasks. Secondly, one of the roles of the physician is to act as the individual patient’s advocate. Therefore, he or she may face conflicts of interest when wishing to act in that person’s best interests while also abiding by the principles of utilitarianism.

The remaining options are that society, through one of its agents, should be vested with this task, or such initiatives should be taken by independent expert professional bodies or a combination of the above with engagement of other stakeholders (not least patients themselves). The absence of such mechanisms places by default the drug manufacturers and health providers in a position of ultimate control of pricing, subject almost entirely to market forces.

In some countries (UK, Germany, France Canada, and Australia), government bodies review efficacy, safety, and cost and determine whether funding should become available from public sources for a drug (38). In the USA, there are no such government funded bodies, though organisations exist that inform clinicians and the public, notably the Institute for Clinical and Economic Review (https://icer.org/) and the Choosing Wisely Campaign of the American Board of Internal Medicine Foundation (https://www.choosingwisely.org/our-mission/). In some cases, professional organisations (e.g. the American Society of Clinical Oncology) (38) have engaged actively towards equal access of patients to the highest quality of care at the lowest cost, with positive results (39). The recently published Joint American and European Thyroid Association Consensus Statement on TED recognises the importance of the above and states: ‘there is a case for all stakeholders, including professional organisations, insurers, health care providers, patients and their advocates, and drug manufacturers, to engage in discussions on how costly treatments for TED can be made more accessible’ (9).

Current status of TEP use

A survey of members of the European Thyroid Association (ETA) and American Thyroid Association (ATA) undertaken in 2021 demonstrated a wide choice difference for first-line treatment in patients with moderate-to-severe active TED. Intravenous glucocorticoids were favoured by 73% of European endocrinologists in comparison to 42% of their transatlantic counterparts. TEP was the first-line preference by 37% of American endocrinologists compared to only 2% by European endocrinologists (40). This confirmed the impression shared by the leadership of both professional organisations that there was a need for joint guidance of their members, which ultimately led to the publication of the Joint American Thyroid Association and European Thyroid Association Consensus Statement on TED at the end of 2022 (9).

Framework for recommendations on the use of TEP

Given the available evidence and the limitations of current knowledge of TEP, what should be the recommendations on its use in clinical practice? Leaving cost-effectiveness aside, it is important to identify which indications are based on high-quality evidence and conversely those that are not. The two RCTs (15, 16) provide such evidence for the use of TEP. Thus, patients that met the following criteria would be candidates for TEP: aged 18–80 years with a disease duration <9 months; CAS ≥4/7, moderate-to-severe disease; no previous exposure to glucocorticoids other than 1 g or less of oral glucocorticoid or other treatments for TED; no evidence of dysthyroid optic neuropathy; not pregnant or breastfeeding; and with no spontaneous improvement in the preceding 2–6 weeks. As the principal advantage of TEP over other medical treatments is the reduction in proptosis, one additional indication for treatment is the inclusion criterion of the second RCT (16), that is a proptosis of ≥3 mm above normal values for race and sex. The evidence for the efficacy of TEP outside the above indications is from uncontrolled observational studies and requires further corroboration (19, 20, 21, 23).

The Joint American and European Thyroid Association Consensus Statement (summarised in Box 1) highlights that the indications and exclusions for TED should align with the RCT evidence that demonstrated efficacy, until high-quality evidence emerges for additional indications. It also draws attention to the fact that key to appropriate decisions is the careful consideration of the potential patient gains and losses of conventional treatment compared to TEP in the context of a number of as yet unknowns and the specific clinical and other characteristics of the individual patient. Previous experience and the literature suggest that the best way of resolving this is through a shared decision-making protocol (41).

Box 1

Reiteration of the recommendations by the Joint American Thyroid Association and European Thyroid Association (9) on treatment of active, moderate-to-severe thyroid eye disease and the use of teprotumumab.

  • Teprotumumab is preferable for patients whose principal feature is proptosis and/or diplopia, if the drug is accessible.

  • Intravenous glucocorticoids remain the treatment of choice for patients whose principal clinical feature is soft tissue inflammation.

  • Teprotumumab may be considered in patients whose principal feature is soft tissue inflammation, and there are prevailing special circumstances, for instance in patients who are intolerant to or have serious contraindications to glucocorticoids, and watchful monitoring is unacceptable.

The European Group on Graves’ Orbitopathy (EUGOGO) updated its guidance a year before the Joint American and European Thyroid Association Consensus Statement. EUGOGO’s recommendation is that TEP may be used as a second-line treatment for TED, given the limitations imposed by the absence of long-term data, no comparative data to other established treatments, non-availability outside the USA, and high cost (42). Instead, EUGOGO recommended intravenous glucocorticoids in combination with mycophenolate as a first-line treatment for moderate-to-severe active TED, based on two RCTs, one of which showed superior efficacy for the combined treatment only in a post hoc analysis (43) while the other (44) has since been retracted (45). Thus, a shadow has been cast on the applicability of EUGOGO’s first-line recommendation, which needs to be addressed.

Wonder drug or great divider?

In the USA, thousands of patients with TED who are covered by health insurance seem to have benefited from receiving TEP. For the 30 million Americans without health insurance, Europeans, and the rest of the world, access of patients with TED to TEP is extremely limited to those taking part in RCTs and those who are sufficiently wealthy to afford it. Licensing by the European Medicines Agency is expected in the foreseeable future. However, if pricing is set at a similar level as in the USA, there is a significant risk that national agencies who appraise new drugs may recommend against public funding of the drug, thus widening the inequality gap. ‘Wonder’ drugs are rare, but TEP is as close to being one as any, particularly with respect to its capacity to reduce proptosis so effectively. However, its extraordinarily high price may also gain it the title of the ‘great divider’ for exposing inequity of access of patients with TED to health care.

Thus far, thyroidology has been relatively unaffected by the emergence of novel, expensive health technologies, with the exceptions of those that relate to advanced thyroid cancer, which have been handled largely through oncology channels. The licensing of TEP at its current cost heralds a new era in thyroidology, with several other products in development that will follow, which are likely to be be costly and to pose similar questions.

The ETA and ATA are the leading professional organisations globally in thyroidology with a large following and influence. One among the stated ETA objectives is ‘To raise the standards of understanding and clinical practice in thyroid disease’ (https://www.eurothyroid.com/about/general_information.html), while the mission statement of the ATA states ‘Transforming thyroid care through clinical excellence, education, scientific discovery and advocacy in a collaborative community’ (https://www.thyroid.org/about-american-thyroid-association/). In accordance with their vision, the ETA and ATA may choose to face these challenges.

Conclusions

TEP represents a significant advance in therapeutics for TED. The high cost, lack of knowledge about cost-effectiveness, and limited availability are barriers to its use. Professional thyroid organisations have the opportunity to lead in finding ways to facilitate making novel treatments available to all thyroid patients who would potentially benefit. Future directions of research ought to address the knowledge gap relating to refining end points in the assessment of patients with TED in RCTs and cost-effectiveness.

Declaration of interest

PP has received honoraria from IBSA. PP was a co-author of the ‘Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association’ (9). LH has received honoraria from IBSA, Lundbeck, Merck, and Horizon Therapeutics PLC.

Funding

No funding to declare.

Author contribution statement

Both authors conceived and developed the theme. PP drafted the initial manuscript. Both authors reviewed and revised the manuscript to its final version.

References

  • 1

    Smith TJ, Hegedus L. Graves' disease. New England Journal of Medicine 2016 375 15521565. (https://doi.org/10.1056/NEJMra1510030)

  • 2

    Perros P, Hegedus L, Bartalena L, Marcocci C, Kahaly GJ, Baldeschi L, Salvi M, Lazarus JH, Eckstein A & Pitz S et al.Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' orbitopathy (EUGOGO) position statement. Orphanet Journal of Rare Diseases 2017 12 72. (https://doi.org/10.1186/s13023-017-0625-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Wiersinga WM. Quality of life in Graves' ophthalmopathy. Best Practice and Research. Clinical Endocrinology and Metabolism 2012 26 359370. (https://doi.org/10.1016/j.beem.2011.11.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Sharma A, Stan MN, & Rootman DB. Measuring health-related quality of life in thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S27S35. (https://doi.org/10.1210/clinem/dgac230)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Ponto KA, Merkesdal S, Hommel G, Pitz S, Pfeiffer N, & Kahaly GJ. Public health relevance of Graves' orbitopathy. Journal of Clinical Endocrinology and Metabolism 2013 98 145152. (https://doi.org/10.1210/jc.2012-3119)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brandt F, Thvilum M, Hegedus L, & Brix TH. Hyperthyroidism is associated with work disability and loss of labour market income. A Danish register-based study in singletons and disease-discordant twin pairs. European Journal of Endocrinology 2015 173 595602. (https://doi.org/10.1530/EJE-15-0306)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Schwensen CF, Brandt F, Hegedus L, & Brix TH. Mortality in Graves' orbitopathy is increased and influenced by gender, age and pre-existing morbidity: a nationwide Danish register study. European Journal of Endocrinology 2017 176 669676. (https://doi.org/10.1530/EJE-16-0954)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Ferlov-Schwensen C, Brix TH, & Hegedus L. Death by suicide in Graves' disease and Graves' orbitopathy: a nationwide Danish register study. Thyroid 2017 27 14751480. (https://doi.org/10.1089/thy.2017.0365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, Mombaerts I, Salvi M, & Stan MN. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. European Thyroid Journal 2022 11 e220189. (https://doi.org/10.1530/ETJ-22-0189)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi G, et al.Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy. Journal of Clinical Endocrinology and Metabolism 2012 97 44544463. (https://doi.org/10.1210/jc.2012-2389)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Krieger CC, Neumann S, & Gershengorn MC. TSH/IGF1 receptor crosstalk: mechanism and clinical implications. Pharmacology and Therapeutics 2020 209 107502. (https://doi.org/10.1016/j.pharmthera.2020.107502)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Smith TJ. Understanding pathogenesis intersects with effective treatment for thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S13S26. (https://doi.org/10.1210/clinem/dgac328)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Girnita L, Smith TJ, & Janssen JAMJL. It takes two to tango: IGF-I and TSH receptors in thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S1S12. (https://doi.org/10.1210/clinem/dgac045)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Smith TJ. Thyroid-associated ophthalmopathy: emergence of teprotumumab as a promising medical therapy. Best Practice and Research. Clinical Endocrinology and Metabolism 2020 34 101383. (https://doi.org/10.1016/j.beem.2020.101383)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, et al.Teprotumumab for thyroid-associated ophthalmopathy. New England Journal of Medicine 2017 376 17481761. (https://doi.org/10.1056/NEJMoa1614949)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marino M, et al.Teprotumumab for the treatment of active thyroid eye disease. New England Journal of Medicine 2020 382 341352. (https://doi.org/10.1056/NEJMoa1910434)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Douglas RS, Kahaly GJ, Ugradar S, Elflein H, Ponto KA, Fowler BT, Dailey R, Harris GJ, Schiffman J, Tang R, et al.Teprotumumab efficacy, safety, and durability in longer-duration thyroid eye disease and re-treatment: OPTIC-X study. Ophthalmology 2022 129 438449. (https://doi.org/10.1016/j.ophtha.2021.10.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    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 and Endocrinology 2021 9 360372. (https://doi.org/10.1016/S2213-8587(2100056-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Ugradar S, Wang Y, Mester T, Kahaly GJ, & Douglas R. Improvement of asymmetric thyroid eye disease with teprotumumab. British Journal of Ophthalmology 2022 106 755759. (https://doi.org/10.1136/bjophthalmol-2020-318314)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Ugradar S, Kang J, Kossler AL, Zimmerman E, Braun J, Harrison AR, Bose S, Cockerham K, & Douglas RS. Teprotumumab for the treatment of chronic thyroid eye disease. Eye 2022 36 15531559. (https://doi.org/10.1038/s41433-021-01593-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Sears CM, Azad AD, Dosiou C, & Kossler AL. Teprotumumab for dysthyroid optic neuropathy: early response to therapy. Ophthalmic Plastic and Reconstructive Surgery 2021 37 S157S160. (https://doi.org/10.1097/IOP.0000000000001831)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Ozzello DJ, Kikkawa DO, & Korn BS. Early experience with teprotumumab for chronic thyroid eye disease. American Journal of Ophthalmology Case Reports 2020 19 100744. (https://doi.org/10.1016/j.ajoc.2020.100744)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Ozzello DJ, Dallalzadeh LO, & Liu CY. Teprotumumab for chronic thyroid eye disease. Orbit 2022 41 539546. (https://doi.org/10.1080/01676830.2021.1933081)

  • 24

    Diniz SB, Cohen LM, Roelofs KA, & Rootman DB. Early experience with the clinical use of teprotumumab in a heterogenous thyroid eye disease population. Ophthalmic Plastic and Reconstructive Surgery 2021 37 583591. (https://doi.org/10.1097/IOP.0000000000001959)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Chiou CA, Reshef ER, & Freitag SK. Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: a report of two cases. American Journal of Ophthalmology Case Reports 2021 22 101075. (https://doi.org/10.1016/j.ajoc.2021.101075)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Bartalena L, & Wiersinga WM. Proposal for standardization of primary and secondary outcomes in patients with active, moderate-to-severe Graves' orbitopathy. European Thyroid Journal 2020 9(Supplement 1) 316. (https://doi.org/10.1159/000510700)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, et al.Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. European Journal of Endocrinology 2008 158 273285. (https://doi.org/10.1530/EJE-07-0666)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Bahn RS, & Gorman CA. Choice of therapy and criteria for assessing treatment outcome in thyroid-associated ophthalmopathy. Endocrinology and Metabolism Clinics of North America 1987 16 391407. (https://doi.org/10.1016/S0889-8529(1830485-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Terwee CB, Gerding MN, Dekker FW, Prummel MF, & Wiersinga WM. Development of a disease specific quality of life questionnaire for patients with Graves' ophthalmopathy: the GO-QOL. British Journal of Ophthalmology 1998 82 773779. (https://doi.org/10.1136/bjo.82.7.773)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Watt T, Hegedus L, Groenvold M, Bjorner JB, Rasmussen AK, Bonnema SJ, & Feldt-Rasmussen U. Validity and reliability of the novel thyroid-specific quality of life questionnaire, ThyPRO. European Journal of Endocrinology 2010 162 161167. (https://doi.org/10.1530/EJE-09-0521)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Douglas RS, Wang Y, Dailey RA, Harris GJ, Wester ST, Schiffman JS, Tang RA, Fowler B, Fleming J, & Smith TJ. Teprotumumab in clinical practice: recommendations and considerations from the OPTIC trial investigators. Journal of Neuro-Ophthalmology 2021 41 461468. (https://doi.org/10.1097/WNO.0000000000001134)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Hwang CJ, Nichols EE, Chon BH, & Perry JD. Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab. European Journal of Ophthalmology 2022 32 NP46NP49. (https://doi.org/10.1177/1120672121991042)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Belinsky I, Creighton FX Jr, Mahoney N, Petris CK, Callahan AB, Campbell AA, Kazim M, Lee HBH, Yoon MK, & Dagi Glass LR. Teprotumumab and hearing loss: case series and proposal for audiologic monitoring. Ophthalmic Plastic and Reconstructive Surgery 2022 38 7378. (https://doi.org/10.1097/IOP.0000000000001995)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Bartalena L, Marino M, Marcocci C, & Tanda ML. Teprotumumab for Graves' orbitopathy and ototoxicity: moving problems from eyes to ears? Journal of Endocrinological Investigation 2022 45 14551457. (https://doi.org/10.1007/s40618-022-01791-w)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Sears CM, Azad AD, Amarikwa L, Pham BH, Men CJ, Kaplan DN, Liu J, Hoffman AR, Swanson A, Alyono J, et al.Hearing dysfunction after treatment with teprotumumab for thyroid eye disease. American Journal of Ophthalmology 2022 240 113. (https://doi.org/10.1016/j.ajo.2022.02.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Langericht J, Kramer I, & Kahaly GJ. Glucocorticoids in Graves' orbitopathy: mechanisms of action and clinical application. Therapeutic Advances in Endocrinology and Metabolism 2020 11 2042018820958335. (https://doi.org/10.1177/2042018820958335)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Stan MN, & Salvi M. MANAGEMENT OF ENDOCRINE DISEASE: rituximab therapy for Graves' orbitopathy - lessons from randomized control trials. European Journal of Endocrinology 2017 176 R101R109. (https://doi.org/10.1530/EJE-16-0552)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Schnipper LE, Davidson NE, Wollins DS, Tyne C, Blayney DW, Blum D, Dicker AP, Ganz PA, Hoverman JR, Langdon R, et al.American Society of Clinical Oncology Statement: A conceptual framework to assess the value of cancer treatment options. Journal of Clinical Oncology 2015 33 25632577. (https://doi.org/10.1200/JCO.2015.61.6706)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Meropol NJ, Schrag D, Smith TJ, Mulvey TM, Langdon RM Jr, Blum D, Ubel PA, Schnipper LE & American Society of Clinical Oncology. American Society of Clinical Oncology guidance statement: the cost of cancer care. Journal of Clinical Oncology 2009 27 38683874. (https://doi.org/10.1200/JCO.2009.23.1183)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Brito JP, Nagy EV, Singh Ospina N, Za M, Dosiou C, Fichter N, Lucarelli MJ, & Hegedus L. A survey on the management of thyroid eye disease among American and European thyroid association members. Thyroid 2022 32 15351546. (https://doi.org/10.1089/thy.2022.0172)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Dobler CC, Guyatt GH, Wang Z, & Murad MH. Users' guide to medical decision analysis. Mayo Clinic Proceedings 2021 96 22052217. (https://doi.org/10.1016/j.mayocp.2021.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marino M, Vaidya B, Wiersinga WM & EUGOGO †. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. European Journal of Endocrinology 2021 185 G43G67. (https://doi.org/10.1530/EJE-21-0479)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Kahaly GJ, Riedl M, Konig J, Pitz S, Ponto K, Diana T, Kampmann E, Kolbe E, Eckstein A, Moeller LC, et al.Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet. Diabetes and Endocrinology 2018 6 287298. (https://doi.org/10.1016/S2213-8587(1830020-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Ye X, Bo X, Hu X, Cui H, Lu B, Shao J, & Wang J. Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves' orbitopathy. Clinical Endocrinology 2017 86 247255. (https://doi.org/10.1111/cen.13170)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Ye X, Bo X, Hu X, Cui H, Lu B, Shao J, & Wang J. Retraction. In Clinical Endocrinology (Oxford) 2023 98 743. (https://doi.org/10.1111/cen.14888)

 

  • Collapse
  • Expand
  • 1

    Smith TJ, Hegedus L. Graves' disease. New England Journal of Medicine 2016 375 15521565. (https://doi.org/10.1056/NEJMra1510030)

  • 2

    Perros P, Hegedus L, Bartalena L, Marcocci C, Kahaly GJ, Baldeschi L, Salvi M, Lazarus JH, Eckstein A & Pitz S et al.Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' orbitopathy (EUGOGO) position statement. Orphanet Journal of Rare Diseases 2017 12 72. (https://doi.org/10.1186/s13023-017-0625-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Wiersinga WM. Quality of life in Graves' ophthalmopathy. Best Practice and Research. Clinical Endocrinology and Metabolism 2012 26 359370. (https://doi.org/10.1016/j.beem.2011.11.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Sharma A, Stan MN, & Rootman DB. Measuring health-related quality of life in thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S27S35. (https://doi.org/10.1210/clinem/dgac230)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Ponto KA, Merkesdal S, Hommel G, Pitz S, Pfeiffer N, & Kahaly GJ. Public health relevance of Graves' orbitopathy. Journal of Clinical Endocrinology and Metabolism 2013 98 145152. (https://doi.org/10.1210/jc.2012-3119)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brandt F, Thvilum M, Hegedus L, & Brix TH. Hyperthyroidism is associated with work disability and loss of labour market income. A Danish register-based study in singletons and disease-discordant twin pairs. European Journal of Endocrinology 2015 173 595602. (https://doi.org/10.1530/EJE-15-0306)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Schwensen CF, Brandt F, Hegedus L, & Brix TH. Mortality in Graves' orbitopathy is increased and influenced by gender, age and pre-existing morbidity: a nationwide Danish register study. European Journal of Endocrinology 2017 176 669676. (https://doi.org/10.1530/EJE-16-0954)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Ferlov-Schwensen C, Brix TH, & Hegedus L. Death by suicide in Graves' disease and Graves' orbitopathy: a nationwide Danish register study. Thyroid 2017 27 14751480. (https://doi.org/10.1089/thy.2017.0365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Burch HB, Perros P, Bednarczuk T, Cooper DS, Dolman PJ, Leung AM, Mombaerts I, Salvi M, & Stan MN. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. European Thyroid Journal 2022 11 e220189. (https://doi.org/10.1530/ETJ-22-0189)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi G, et al.Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy. Journal of Clinical Endocrinology and Metabolism 2012 97 44544463. (https://doi.org/10.1210/jc.2012-2389)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Krieger CC, Neumann S, & Gershengorn MC. TSH/IGF1 receptor crosstalk: mechanism and clinical implications. Pharmacology and Therapeutics 2020 209 107502. (https://doi.org/10.1016/j.pharmthera.2020.107502)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Smith TJ. Understanding pathogenesis intersects with effective treatment for thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S13S26. (https://doi.org/10.1210/clinem/dgac328)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Girnita L, Smith TJ, & Janssen JAMJL. It takes two to tango: IGF-I and TSH receptors in thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S1S12. (https://doi.org/10.1210/clinem/dgac045)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Smith TJ. Thyroid-associated ophthalmopathy: emergence of teprotumumab as a promising medical therapy. Best Practice and Research. Clinical Endocrinology and Metabolism 2020 34 101383. (https://doi.org/10.1016/j.beem.2020.101383)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, et al.Teprotumumab for thyroid-associated ophthalmopathy. New England Journal of Medicine 2017 376 17481761. (https://doi.org/10.1056/NEJMoa1614949)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marino M, et al.Teprotumumab for the treatment of active thyroid eye disease. New England Journal of Medicine 2020 382 341352. (https://doi.org/10.1056/NEJMoa1910434)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Douglas RS, Kahaly GJ, Ugradar S, Elflein H, Ponto KA, Fowler BT, Dailey R, Harris GJ, Schiffman J, Tang R, et al.Teprotumumab efficacy, safety, and durability in longer-duration thyroid eye disease and re-treatment: OPTIC-X study. Ophthalmology 2022 129 438449. (https://doi.org/10.1016/j.ophtha.2021.10.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    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 and Endocrinology 2021 9 360372. (https://doi.org/10.1016/S2213-8587(2100056-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Ugradar S, Wang Y, Mester T, Kahaly GJ, & Douglas R. Improvement of asymmetric thyroid eye disease with teprotumumab. British Journal of Ophthalmology 2022 106 755759. (https://doi.org/10.1136/bjophthalmol-2020-318314)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Ugradar S, Kang J, Kossler AL, Zimmerman E, Braun J, Harrison AR, Bose S, Cockerham K, & Douglas RS. Teprotumumab for the treatment of chronic thyroid eye disease. Eye 2022 36 15531559. (https://doi.org/10.1038/s41433-021-01593-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Sears CM, Azad AD, Dosiou C, & Kossler AL. Teprotumumab for dysthyroid optic neuropathy: early response to therapy. Ophthalmic Plastic and Reconstructive Surgery 2021 37 S157S160. (https://doi.org/10.1097/IOP.0000000000001831)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Ozzello DJ, Kikkawa DO, & Korn BS. Early experience with teprotumumab for chronic thyroid eye disease. American Journal of Ophthalmology Case Reports 2020 19 100744. (https://doi.org/10.1016/j.ajoc.2020.100744)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Ozzello DJ, Dallalzadeh LO, & Liu CY. Teprotumumab for chronic thyroid eye disease. Orbit 2022 41 539546. (https://doi.org/10.1080/01676830.2021.1933081)

  • 24

    Diniz SB, Cohen LM, Roelofs KA, & Rootman DB. Early experience with the clinical use of teprotumumab in a heterogenous thyroid eye disease population. Ophthalmic Plastic and Reconstructive Surgery 2021 37 583591. (https://doi.org/10.1097/IOP.0000000000001959)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Chiou CA, Reshef ER, & Freitag SK. Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: a report of two cases. American Journal of Ophthalmology Case Reports 2021 22 101075. (https://doi.org/10.1016/j.ajoc.2021.101075)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Bartalena L, & Wiersinga WM. Proposal for standardization of primary and secondary outcomes in patients with active, moderate-to-severe Graves' orbitopathy. European Thyroid Journal 2020 9(Supplement 1) 316. (https://doi.org/10.1159/000510700)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, et al.Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. European Journal of Endocrinology 2008 158 273285. (https://doi.org/10.1530/EJE-07-0666)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Bahn RS, & Gorman CA. Choice of therapy and criteria for assessing treatment outcome in thyroid-associated ophthalmopathy. Endocrinology and Metabolism Clinics of North America 1987 16 391407. (https://doi.org/10.1016/S0889-8529(1830485-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Terwee CB, Gerding MN, Dekker FW, Prummel MF, & Wiersinga WM. Development of a disease specific quality of life questionnaire for patients with Graves' ophthalmopathy: the GO-QOL. British Journal of Ophthalmology 1998 82 773779. (https://doi.org/10.1136/bjo.82.7.773)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Watt T, Hegedus L, Groenvold M, Bjorner JB, Rasmussen AK, Bonnema SJ, & Feldt-Rasmussen U. Validity and reliability of the novel thyroid-specific quality of life questionnaire, ThyPRO. European Journal of Endocrinology 2010 162 161167. (https://doi.org/10.1530/EJE-09-0521)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Douglas RS, Wang Y, Dailey RA, Harris GJ, Wester ST, Schiffman JS, Tang RA, Fowler B, Fleming J, & Smith TJ. Teprotumumab in clinical practice: recommendations and considerations from the OPTIC trial investigators. Journal of Neuro-Ophthalmology 2021 41 461468. (https://doi.org/10.1097/WNO.0000000000001134)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Hwang CJ, Nichols EE, Chon BH, & Perry JD. Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab. European Journal of Ophthalmology 2022 32 NP46NP49. (https://doi.org/10.1177/1120672121991042)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Belinsky I, Creighton FX Jr, Mahoney N, Petris CK, Callahan AB, Campbell AA, Kazim M, Lee HBH, Yoon MK, & Dagi Glass LR. Teprotumumab and hearing loss: case series and proposal for audiologic monitoring. Ophthalmic Plastic and Reconstructive Surgery 2022 38 7378. (https://doi.org/10.1097/IOP.0000000000001995)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Bartalena L, Marino M, Marcocci C, & Tanda ML. Teprotumumab for Graves' orbitopathy and ototoxicity: moving problems from eyes to ears? Journal of Endocrinological Investigation 2022 45 14551457. (https://doi.org/10.1007/s40618-022-01791-w)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Sears CM, Azad AD, Amarikwa L, Pham BH, Men CJ, Kaplan DN, Liu J, Hoffman AR, Swanson A, Alyono J, et al.Hearing dysfunction after treatment with teprotumumab for thyroid eye disease. American Journal of Ophthalmology 2022 240 113. (https://doi.org/10.1016/j.ajo.2022.02.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Langericht J, Kramer I, & Kahaly GJ. Glucocorticoids in Graves' orbitopathy: mechanisms of action and clinical application. Therapeutic Advances in Endocrinology and Metabolism 2020 11 2042018820958335. (https://doi.org/10.1177/2042018820958335)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Stan MN, & Salvi M. MANAGEMENT OF ENDOCRINE DISEASE: rituximab therapy for Graves' orbitopathy - lessons from randomized control trials. European Journal of Endocrinology 2017 176 R101R109. (https://doi.org/10.1530/EJE-16-0552)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Schnipper LE, Davidson NE, Wollins DS, Tyne C, Blayney DW, Blum D, Dicker AP, Ganz PA, Hoverman JR, Langdon R, et al.American Society of Clinical Oncology Statement: A conceptual framework to assess the value of cancer treatment options. Journal of Clinical Oncology 2015 33 25632577. (https://doi.org/10.1200/JCO.2015.61.6706)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Meropol NJ, Schrag D, Smith TJ, Mulvey TM, Langdon RM Jr, Blum D, Ubel PA, Schnipper LE & American Society of Clinical Oncology. American Society of Clinical Oncology guidance statement: the cost of cancer care. Journal of Clinical Oncology 2009 27 38683874. (https://doi.org/10.1200/JCO.2009.23.1183)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Brito JP, Nagy EV, Singh Ospina N, Za M, Dosiou C, Fichter N, Lucarelli MJ, & Hegedus L. A survey on the management of thyroid eye disease among American and European thyroid association members. Thyroid 2022 32 15351546. (https://doi.org/10.1089/thy.2022.0172)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Dobler CC, Guyatt GH, Wang Z, & Murad MH. Users' guide to medical decision analysis. Mayo Clinic Proceedings 2021 96 22052217. (https://doi.org/10.1016/j.mayocp.2021.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marino M, Vaidya B, Wiersinga WM & EUGOGO †. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. European Journal of Endocrinology 2021 185 G43G67. (https://doi.org/10.1530/EJE-21-0479)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Kahaly GJ, Riedl M, Konig J, Pitz S, Ponto K, Diana T, Kampmann E, Kolbe E, Eckstein A, Moeller LC, et al.Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial. Lancet. Diabetes and Endocrinology 2018 6 287298. (https://doi.org/10.1016/S2213-8587(1830020-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Ye X, Bo X, Hu X, Cui H, Lu B, Shao J, & Wang J. Efficacy and safety of mycophenolate mofetil in patients with active moderate-to-severe Graves' orbitopathy. Clinical Endocrinology 2017 86 247255. (https://doi.org/10.1111/cen.13170)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Ye X, Bo X, Hu X, Cui H, Lu B, Shao J, & Wang J. Retraction. In Clinical Endocrinology (Oxford) 2023 98 743. (https://doi.org/10.1111/cen.14888)