Advertisement

Teprotumumab

A Major Advance in the Treatment of Thyroid Eye Disease Management

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Advances in Ophthalmology and Optometry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Abraham-Nordling M.
        • Bystrom K.
        • Torring O.
        • et al.
        Incidence of hyperthyroidism in Sweden.
        Eur J Endocrinol. 2011; 165: 899-905
        • Bartley G.B.
        The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota.
        Trans Am Ophthalmol Soc. 1994; 92: 477-588
        • Chin Y.H.
        • Ng C.H.
        • Lee M.H.
        • et al.
        Prevalence of thyroid eye disease in Graves' disease: A meta-analysis and systematic review.
        Clin Endocrinol. 2020; 93: 363-374
        • Bartalena L.
        • Piantanida E.
        • Gallo D.
        • et al.
        Epidemiology, natural history, risk factors, and prevention of Graves' orbitopathy.
        Front Endocrinol. 2020; 11: 615993
        • Kahaly G.J.
        • Petrak F.
        • Hardt J.
        • et al.
        Psychosocial morbidity of Graves' orbitopathy.
        Clin Endocrinol. 2005; 63: 395-402
        • Park J.J.
        • Sullivan T.J.
        • Mortimer R.H.
        • et al.
        Assessing quality of life in Australian patients with Graves' ophthalmopathy.
        Br J Ophthalmol. 2004; 88: 75-78
        • Ferløv-Schwensen C.
        • Brix T.H.
        • Hegedüs L.
        Death by Suicide in Graves' Disease and Graves' Orbitopathy: A Nationwide Danish Register Study.
        Thyroid. 2017; 27: 1475-1480
        • Rundle F.F.
        Management of exophthalmos and related ocular changes in Graves' disease.
        Metabolism. 1957; 6: 36-48
        • Tanda M.L.
        • Piantanida E.
        • Liparulo L.
        • et al.
        Prevalence and natural history of Graves’ orbitopathy in a large series of patients with newly diagnosed Graves’ hyperthyroidism seen at a single center.
        J Clin Endocrinol Metab. 2013; 98: 1443-1449
        • Bahn R.S.
        Graves' ophthalmopathy.
        N Engl J Med. 2010; 362: 726-738
        • Barrio-Barrio J.
        • Sabater A.L.
        • Bonet-Farriol E.
        • et al.
        Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management.
        J Ophthalmol. 2015; 2015: 249125
        • Biondi B.
        • Bartalena L.
        • Cooper D.S.
        • et al.
        The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism.
        Eur Thyroid J. 2015; 4: 149-163
        • Mourits M.P.
        • Prummel M.F.
        • Wiersinga W.M.
        • et al.
        Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy.
        Clin Endocrinol. 1997; 47: 9-14
        • Werner S.C.
        Modification of the classification of the eye changes of Graves' disease.
        Am J Ophthalmol. 1977; 83: 725-727
        • Dolman P.J.
        • Rootman J.
        VISA classification for Graves orbitopathy.
        Ophthal Plast Reconstr Surg. 2006; 22: 319-324
        • Bartalena L.
        • Baldeschi L.
        • Dickinson A.
        • et al.
        Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO.
        Eur J Endocrinol. 2008; 158: 273-285
        • Bartley G.B.
        • Fatourechi V.
        • Kadrmas E.F.
        • et al.
        The treatment of Graves' ophthalmopathy in an incidence cohort.
        Am J Ophthalmol. 1996; 121: 200-206
        • Bartalena L.
        • Kahaly G.J.
        • Baldeschi L.
        • et al.
        The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy.
        Eur J Endocrinol. 2021; 185: G43-G67
        • Marcocci C.
        • Kahaly G.J.
        • Krassas G.E.
        • et al.
        Selenium and the course of mild Graves' orbitopathy.
        N Engl J Med. 2011; 364: 1920-1931
        • Bradley E.A.
        • Gower E.W.
        • Bradley D.J.
        • et al.
        Orbital radiation for graves ophthalmopathy: a report by the American Academy of Ophthalmology.
        Ophthalmology. 2008; 115: 398-409
        • Rajendram R.
        • Bunce C.
        • Lee R.W.J.
        • et al.
        Orbital radiotherapy for adult thyroid eye disease.
        Cochrane Database Syst Rev. 2012; 7: CD007114
        • Shams P.N.
        • Ma R.
        • Pickles T.
        • et al.
        Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease.
        Am J Ophthalmol. 2014; 157: 1299-1305
        • Kazim M.
        • Trokel S.
        • Moore S.
        Treatment of acute Graves orbitopathy.
        Ophthalmology. 1991; 98: 1443-1448
        • Wakelkamp I.M.
        • Tan H.
        • Saeed P.
        • et al.
        Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study.
        Ophthalmology. 2004; 111: 1557-1562
        • Zang S.
        • Ponto K.A.
        • Kahaly G.J.
        Clinical review: intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity.
        J Clin Endocrinol Metab. 2011; 96: 320-332
        • Tu X.
        • Dong Y.
        • Zhang H.
        • et al.
        Corticosteroids for Graves' ophthalmopathy: systematic review and meta-analysis.
        Biomed Res Int. 2018; 2018: 4845894
        • van Geest R.J.
        • Sasim I.V.
        • Koppeschaar H.P.
        • et al.
        Methylprednisolone pulse therapy for patients with moderately severe Graves' orbitopathy: a prospective, randomized, placebo-controlled study.
        Eur J Endocrinol. 2008; 158: 229-237
        • Stan M.N.
        • Garrity J.A.
        • Carranza Leon B.G.
        • et al.
        Randomized controlled trial of rituximab in patients with Graves' orbitopathy.
        J Clin Endocrinol Metab. 2015; 100: 432-441
        • Perez-Moreiras J.V.
        • Gomez-Reino J.J.
        • Maneiro J.R.
        • et al.
        Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant graves orbitopathy: a randomized clinical trial.
        Am J Ophthalmol. 2018; 195: 181-190
        • Borumandi F.
        • Hammer B.
        • Kamer L.
        • et al.
        How predictable is exophthalmos reduction in Graves' orbitopathy? A review of the literature.
        Br J Ophthalmol. 2011; 95: 1625-1630
        • Jefferis J.M.
        • Jones R.K.
        • Currie Z.I.
        • et al.
        Orbital decompression for thyroid eye disease: methods, outcomes, and complications.
        Eye. 2018; 32: 626-636
        • Ben Simon G.J.
        • Wang L.L.
        • McCann J.D.
        • et al.
        Primary-gaze diplopia in patients with thyroid-related orbitopathy undergoing deep lateral orbital decompression with intraconal fat debulking: A retrospective analysis of treatment outcome.
        Thyroid. 2004; 14: 379-383
        • Barker L.
        • Mackenzie K.
        • Adams G.G.
        • et al.
        Long-term surgical outcomes for vertical deviations in thyroid eye disease.
        Strabismus. 2017; 25: 67-72
        • Smith T.J.
        • Kahaly G.J.
        • Ezra D.G.
        • et al.
        Teprotumumab for thyroid-associated ophthalmopathy.
        N Engl J Med. 2017; 376: 1748-1761
        • Douglas R.S.
        • Kahaly G.J.
        • Patel A.
        • et al.
        Teprotumumab for the treatment of active thyroid eye disease.
        N Engl J Med. 2020; 382: 341-352
        • Shan S.J.
        • Douglas R.S.
        The pathophysiology of thyroid eye disease.
        J Neuroophthalmol. 2014; 34: 177-185
        • Khong J.J.
        • McNab A.A.
        • Ebeling P.R.
        • et al.
        Pathogenesis of thyroid eye disease: review and update on molecular mechanisms.
        Br J Ophthalmol. 2016; 100: 142-150
        • Bahn R.S.
        • Dutton C.M.
        • Natt N.
        • et al.
        Thyrotropin receptor expression in Graves’ orbital adipose/connective tissues: potential autoantigen in Graves’ ophthalmopathy.
        J Clin Endocrinol Metab. 1998; 83: 998-1002
        • Smith T.J.
        • Hegedüs L.
        • Douglas R.S.
        Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves' orbitopathy.
        Best Pract Res Clin Endocrinol Metab. 2012; 26: 291-302
        • Janssen J.A.M.J.L.
        • Smith T.J.
        Lessons learned from targeting IGF-I receptor in thyroid-associated ophthalmopathy.
        Cells. 2021; 10: 383
        • Tsui S.
        • Naik V.
        • Hoa N.
        • et al.
        Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves’ disease.
        J Immunol. 2008; 181: 4397-4405
        • Krieger C.C.
        • Place R.F.
        • Bevilacqua C.
        • et al.
        TSH/IGF-1 Receptor Cross Talk in Graves' ophthalmopathy pathogenesis.
        J Clin Endocrinol Metab. 2016; 101: 2340-2347
        • Krieger C.C.
        • Neumann S.
        • Gershengorn M.C.
        TSH/IGF1 receptor crosstalk: mechanism and clinical implications.
        Pharmacol Ther. 2020; 209: 107502
        • Ugradar S.
        • Shi L.
        • Wang Y.
        • et al.
        Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression.
        Eye. 2021; 35: 2607-2612
        • Ventura M.
        • Melo M.
        • Carrilho F.
        Selenium and thyroid disease: from pathophysiology to treatment.
        Int J Endocrinol. 2017; 2017: 1297658
        • Hu Y.
        • Feng W.
        • Chen H.
        • et al.
        Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto's thyroiditis: a prospective randomized-controlled trial.
        Clin Transl Sci. 2021; 14: 1390-1402
        • Sadaka A.
        • Nguyen K.
        • Malik A.
        • et al.
        Vitamin D and selenium in a thyroid eye disease population in Texas.
        Neuroophthalmology. 2019; 43: 291-294
        • Acharya S.H.
        • Avenell A.
        • Philip S.
        • et al.
        Radioiodine therapy (RAI) for Graves' disease (GD) and the effect on ophthalmopathy: a systematic review.
        Clin Endocrinol. 2008; 69: 943-950
        • Lee S.J.
        • Rim T.H.
        • Jang S.Y.
        • et al.
        Treatment of upper eyelid retraction related to thyroid-associated ophthalmopathy using subconjunctival triamcinolone injections.
        Graefes Arch Clin Exp Ophthalmol. 2013; 251: 261-270
        • Currò N.
        • Covelli D.
        • Vannucchi G.
        • et al.
        Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy.
        Thyroid. 2014; 24: 897-905
        • Marcocci C.
        • Bartalena L.
        • Tanda M.L.
        • et al.
        Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study.
        J Clin Endocrinol Metab. 2001; 86: 3562-3567
        • Kahaly G.J.
        • Pitz S.
        • Hommel G.
        • et al.
        Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.
        J Clin Endocrinol Metab. 2005; 90: 5234-5240
        • Bartalena L.
        • Pinchera A.
        • Marcocci C.
        Management of Graves’ ophthalmopathy: reality and perspectives.
        Endocr Rev. 2000; 21: 168-199
        • Sisti E.
        • Menconi F.
        • Leo M.
        • et al.
        Long-term outcome of Graves' orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy.
        J Endocrinol Invest. 2015; 38: 661-668
        • Bartalena L.
        • Marcocci C.
        • Pinchera A.
        Treating severe Graves' ophthalmopathy.
        Baillieres Clin Endocrinol Metab. 1997; 11: 521-536
        • Marino M.
        Acute and severe liver damage associated with intravenous glucocorticoid pulse therapy in patients with Graves’ ophthalmopathy.
        Thyroid. 2004; 14: 403-406
        • Bartalena L.
        • Krassas G.E.
        • Wiersinga W.
        • et al.
        Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy.
        J Clin Endocrinol Metab. 2012; 97: 4454-4463
        • Mourits M.P.
        • van Kempen-Harteveld M.L.
        • García M.B.
        • et al.
        Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study.
        Lancet. 2000; 355: 1505-1509
        • Marcocci C.
        • Bartalena L.
        • Bogazzi F.
        • et al.
        Role of orbital radiotherapy in the treatment of Graves' ophthalmopathy.
        Exp Clin Endocrinol. 1991; 97: 332-337
        • Limone P.P.
        • Bianco L.
        • Mellano M.
        • et al.
        Is concomitant treatment with steroids and radiotherapy more favorable than sequential treatment in moderate-to-severe graves orbitopathy?.
        Radiol Med. 2021; 126: 334-342
        • Ohtsuka K.
        • Sato A.
        • Kawaguchi S.
        • et al.
        Effect of steroid pulse therapy with and without orbital radiotherapy on Graves' ophthalmopathy.
        Am J Ophthalmol. 2003; 135: 285-290
        • Gorman C.A.
        • Garrity J.A.
        • Fatourechi V.
        • et al.
        A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy.
        Ophthalmology. 2001; 108: 1523-1534
        • Russell D.J.
        • Wagner L.H.
        • Seiff S.R.
        Tocilizumab as a steroid sparing agent for the treatment of Graves' orbitopathy.
        Am J Ophthalmol Case Rep. 2017; 7: 146-148
        • Copperman T.
        • Idowu O.O.
        • Kersten R.C.
        • et al.
        Subcutaneous tocilizumab for thyroid eye disease: simplified dosing and delivery.
        Ophthalmic Plast Reconstr Surg. 2019; 35: e64-e66
        • Salvi M.
        • Vannucchi G.
        • Currò N.
        • et al.
        Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves’ orbitopathy: a randomized controlled study.
        J Clin Endocrinol Metab. 2015; 100: 422-431
        • Stan M.N.
        • Garrity J.A.
        • Carranza Leon B.G.
        • et al.
        Randomized controlled trial of rituximab in patients with Graves’ orbitopathy.
        J Clin Endocrinol Metab. 2015; 100: 432-441
        • Vannucchi G.
        • Campi I.
        • Covelli D.
        • et al.
        Efficacy profile and safety of very low-dose rituximab in patients with Graves' orbitopathy.
        Thyroid. 2021; 31: 821-828
        • Ayabe R.
        • Rootman D.B.
        • Hwang C.J.
        • et al.
        Adalimumab as steroid-sparing treatment of inflammatory-stage thyroid eye disease.
        Ophthalmic Plast Reconstr Surg. 2014; 30: 415-419
        • Durrani O.M.
        • Reuser T.Q.
        • Murray P.I.
        Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy.
        Orbit. 2005; 24: 117-119
        • Winn B.J.
        • Kersten R.C.
        Teprotumumab: interpreting the clinical trials in the context of thyroid eye disease pathogenesis and current therapies.
        Ophthalmology. 2021; 128: 1627-1651
        • Xin Y.
        • Xu F.
        • Gao Y.
        • et al.
        Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease.
        Clin Pharmacokinet. 2021; 60: 1029-1040
        • Smith T.J.
        • Kahaly G.J.
        • Ezra D.G.
        • et al.
        Teprotumumab for thyroid-associated ophthalmopathy. Supplementary Material: Protocol.
        N Engl J Med. 2017; 376: 1748-1761
        • Ashraf D.C.
        • Jankovic I.
        • El-Nachef N.
        • et al.
        New-onset of inflammatory bowel disease in a patient treated with teprotumumab for thyroid associated ophthalmopathy.
        Ophthalmic Plast Reconstr Surg. 2021; 37: e160-e164
        • Safo M.B.
        • Silkiss R.Z.
        A case of ulcerative colitis associated with teprotumumab treatment for thyroid eye disease.
        Am J Ophthalmol Case Rep. 2021; 22: 101069
        • Belinsky I.
        • Creighton Jr., F.X.
        • Mahoney N.
        • et al.
        Teprotumumab and hearing loss: case series and proposal for audiologic monitoring.
        Ophthalmic Plast Reconstr Surg. 2021; 38: 73-78
        • Kossler A.
        • Sears C.M.
        • Dosiou C.
        Hearing Loss and Teprotumumab.
        J Endocr Soc. 2021; 5: A839
        • Yu C.Y.
        • Correa T.
        • Simmons B.A.
        • et al.
        Audiology findings in patients with teprotumumab associated otologic symptoms.
        Am J Ophthalmol Case Rep. 2021; 24: 101202
        • Chern A.
        • Gudis D.A.
        • Dagi Glass L.R.
        Teprotumumab and hearing loss: hear the warnings.
        Orbit. 2021; 40: 355-356
        • Rodríguez-de la Rosa L.
        • Lassaletta L.
        • Calvino M.
        • et al.
        The role of insulin-like growth factor 1 in the progression of age-related hearing loss.
        Front Aging Neurosci. 2017; 9: 411
        • Goldman J.W.
        • Mendenhall M.A.
        • Rettinger S.R.
        Hyperglycemia associated with targeted oncologic treatment: mechanisms and management.
        Oncologist. 2016; 21: 1326-1336
        • Lee H.B.H.
        • Mariash C.N.
        • Yoon M.K.
        • et al.
        Teprotumumab and hyperglycemia guidelines to monitor for hyperglycemia in teprotumumab.
        Ophthalmic Plast Reconstr Surg. 2021; 37: 393
        • Hoang T.D.
        • Nguyen N.T.
        • Chou E.
        • et al.
        Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease.
        BMJ Case Rep. 2021; 14: e242153
        • Douglas R.S.
        • Kahaly G.J.
        • Ugradar S.
        • et al.
        Teprotumumab efficacy, safety, and durability in longer-duration thyroid eye disease and re-treatment: OPTIC-X Study.
        Ophthalmology. 2021; S0161-6420: 00818-826
        • Douglas R.S.
        Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis.
        Eye. 2019; 33: 183-190
        • Jain A.P.
        • Gellada N.
        • Ugradar S.
        • et al.
        Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease.
        Br J Ophthalmol. 2020; 106: 165-171
        • Tran C.
        • Pham C.M.
        • Simmons B.A.
        • et al.
        Echographic assessment of extraocular muscle response to teprotumumab.
        Ophthalmic Plast Reconstr Surg. 2021;
        • Kahaly G.J.
        • Douglas R.S.
        • Holt R.J.
        • et al.
        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: 360-3724
        • Hwang C.J.
        • Nichols E.E.
        • Chon B.H.
        • et al.
        Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab.
        Eur J Ophthalmol. 2021; (120672121991042)
        • Sears C.M.
        • Azad A.D.
        • Dosiou C.
        • et al.
        Teprotumumab for dysthyroid optic neuropathy: early response to therapy.
        Ophthalmic Plast Reconstr Surg. 2021; 37: S157-S160
        • Sears C.M.
        • Wang Y.
        • Bailey L.A.
        • et al.
        Early efficacy of teprotumumab for the treatment of dysthyroid optic neuropathy: a multicenter study.
        Am J Ophthalmol Case Rep. 2021; 23: 101111
        • Slentz D.H.
        • Smith T.J.
        • Kim D.S.
        • et al.
        Teprotumumab for optic neuropathy in thyroid eye disease.
        JAMA Ophthalmol. 2021; 139: 244-247
        • Lopez M.J.
        • Herring J.L.
        • Thomas C.
        • et al.
        Visual recovery of dysthyroid optic neuropathy with teprotumumab.
        J Neuroophthalmol. 2021;
        • Chiou C.A.
        • Reshef E.R.
        • Freitag S.K.
        Teprotumumab for the treatment of mild compressive optic neuropathy in thyroid eye disease: a report of two cases.
        Am J Ophthalmol Case Rep. 2021; 22: 101075
        • Diniz S.B.
        • Cohen L.M.
        • Roelofs K.A.
        • et al.
        Early experience with the clinical use of teprotumumab in a heterogenous thyroid eye disease population.
        Ophthalmic Plast Reconstr Surg. 2021; 37: 583-591
        • Ozzello D.J.
        • Kikkawa D.O.
        • Korn B.S.
        Early experience with teprotumumab for chronic thyroid eye disease.
        Am J Ophthalmol Case Rep. 2020; 19: 100744
        • Ozzello D.J.
        • Dallalzadeh L.O.
        • Liu C.Y.
        Teprotumumab for chronic thyroid eye disease.
        Orbit. 2021; : 1-8
        • Ugradar S.
        • Kang J.
        • Kossler A.L.
        • et al.
        Teprotumumab for the treatment of chronic thyroid eye disease.
        Eye (Lond). 2021;
        • Yu C.Y.
        • Simmons B.A.
        • Pham C.M.
        • et al.
        The role of teprotumumab in chronic, clinically active thyroid eye disease.
        Eye (Lond). 2021;
        • Ponto K.A.
        • Merkesdal S.
        • Hommel G.
        • et al.
        Public health relevance of Graves' orbitopathy.
        J Clin Endocrinol Metab. 2013; 98: 145-152
      1. Singh G, Sehgal M, Mithal A, et al. Thyroid eye disease in the United States: data from emergency department visits and hospitalizations. Presented at: 2021 AACE Virtual Annual Meeting, May 26–29, 2021.

        • Neumann S.
        • Krieger C.C.
        • Gershengorn M.C.
        Targeting TSH and IGF-1 Receptors to Treat Thyroid Eye Disease.
        Eur Thyroid J. 2020; 9: 59-65
        • Marcinkowski P.
        • Hoyer I.
        • Specker E.
        • et al.
        A new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of Graves' orbitopathy.
        Thyroid. 2019; 29: 111-123