Top

Published in:

12-09-2023 | Glucocorticoid | Original Paper

Comparison of the efficacy of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves’ orbitopathy

Authors: Mariya Asenova Stoynova, Alexander Dimitrov Shinkov, Inna Dimitrova Dimitrova, Inna Angelova Yankova, Roussanka Dimitrova Kovatcheva

Published in: International Ophthalmology | Issue 12/2023

Abstract

Purpose

Intravenous glucocorticoids (GCs) are the mainstay of treatment for severe forms of Graves’ orbitopathy (GO). Our aim was to assess the effectiveness and safety of a modified monthly regimen (mMR) and to compare them with those of the established weekly regimen (WR).

Methods

This was a prospective non-randomized single-center study involving 62 patients, divided into two therapeutic groups depending on their referral time. Thirty-one subjects, admitted in the period 2017–2018, were treated with mMR, total dose—5.5 g, with intake of oral GCs after completion of intravenous infusions. Thirty subjects, who were referred in the period 2019–2020, were treated with WR, total dose—4.5 g One patient refused to be part of the WR group and was treated with mMR. Eye status and therapeutic response were evaluated on the 1st, 3rd and 6th months, quality of life—at 3rd and 6th month.

Results

At 1st month and 3rd month, there was no significant difference in the therapeutic response between the two groups. At 3rd month, the proportion of patients with improvement in soft tissue manifestations and subjective complaints was significantly higher in mMR group (65.6% vs. 40% and 81.3% vs. 46.7%, respectively) and the same manifestations were of significantly milder degree.

At 3rd month, significant improvement in quality of life was found without significant difference between the two groups.

At 6th month, worsening of GO occurred in 3 patients from WR group, while in 5 patients from mMR group further improvement was found.

Conclusions

The two GC regimens have comparable efficacy with small differences in the time of onset of the effect and its duration, as well as in the effectiveness on some ocular manifestations.

Trial registration number NCT05793359/29.03.2023, retrospectively registered..

van Geest RJ, Sasim IV, Koppeschaar HPF, Kalmann R, Stravers SN, Bijlsma WR, Mourits MP (2008) Methylprednisolone pulse therapy for patients with moderately severe Graves’ orbitopathy: a prospective, randomized, placebo-controlled study. Eur J Endocrinol 158:229–237. https://doi.org/10.1530/EJE-07-0558CrossRefPubMed

Macchia PE, Bagattini M, Lupoli G, Vitale M, Vitale G, Fenzi G (2001) High-dose intravenous corticosteroid therapy for Graves’ ophthalmopathy. J Endocrinol Invest 24:152–158. https://doi.org/10.1007/BF03343835CrossRefPubMed

Kahaly GJ, Pitz S, Hommel G, Dittmar M (2005) Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves’ orbitopathy. J Clin Endocrinol Metab 90:5234–5240. https://doi.org/10.1210/jc.2005-0148CrossRefPubMed

Marcocci C, Bartalena L, Tanda ML, Manetti L, Dell’Unto E, Rocchi R, Barbesino G, Mazzi B, Bartolomei MP, Lepri P (2001) 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 86:3562–3567. https://doi.org/10.1210/jcem.86.8.7737CrossRefPubMed

Aktaran Ş, Akarsu E, Erbağci İ, Araz M, Okumuş S, Kartal M (2006) Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves’ ophthalmopathy. Int J Clin Pract 61:45–51. https://doi.org/10.1111/j.1742-1241.2006.01004.xCrossRefPubMed

Akarsu E, Buyukhatipoglu H, Aktaran Ş, Kurtul N (2011) Effects of pulse methylprednisolone and oral methylprednisolone treatments on serum levels of oxidative stress markers in Graves’ ophthalmopathy. Clin Endocrinol 74:118–124. https://doi.org/10.1111/j.1365-2265.2010.03904.xCrossRef

Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marinò M, Vaidya B, Wiersinga WM (2021) The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol 185:G43-67. https://doi.org/10.1530/EJE-21-0479CrossRefPubMed

Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, Perros P, Salvi M, Wiersinga WM (2016) The 2016 European thyroid association/European group on Graves’ orbitopathy guidelines for the management of Graves’ orbitopathy. Eur Thyroid J 55:9–269. https://doi.org/10.1159/000443828CrossRef

Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi G et al (2012) Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab 97:4454–4463. https://doi.org/10.1210/jc.2012-2389CrossRefPubMed

10.

Nedeljkovic Beleslin B, Ciric J, Stojkovic M, Savic S, Lalic T, Stojanovic M, Miletic M, Knezevic M, Stankovic B (2020) Comparison of efficacy and safety of parenteral versus parenteral and oral glucocorticoid therapy in Graves’ orbitopathy. Int J Clin Pract 74:0–2. https://doi.org/10.1111/ijcp.13608CrossRef

11.

Sánchez-Ortiga R, Moreno-Pérez Ó, González Sánchez V, Arias Mendoza N, Mauri Dot M, Alfayate Guerra R, López Macia A, Picó Alfonso A (2009) Treatment of Graves’ ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens. Endocrinol Y Nutr 56(3):118–122. https://doi.org/10.1016/S1575-0922(09)70841-1CrossRef

12.

Zhu W, Ye L, Shen L, Jiao Q, Huang F, Han R, Zhang X, Wang S, Wang W, Ning G (2014) A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with Graves’ ophthalmopathy. J Clin Endocrinol Metab 99:1999–2007. https://doi.org/10.1210/jc.2013-3919CrossRefPubMed

13.

Mu P-W, Tang X-X, Wang Y-N, Lin S, Wang MM, Yin QL, Shu J, Zhu BL, Li JR, Zhou L (2020) Comparison of two regimens for patients with thyroid-associated ophthalmopathy receiving intravenous methyl prednisolone: a single center prospective randomized trial. Exp Ther Med 20:1–9. https://doi.org/10.3892/etm.2020.9282CrossRef

14.

Roy A, Dutta D, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, Chowdhury S (2015) Efficacy and safety of low dose oral prednisolone as compared to pulse intravenous methylprednisolone in managing moderate severe Graves’ orbitopathy: a randomized controlled trial. Indian J Endocrinol Metab 19:351–358. https://doi.org/10.4103/2230-8210.152770CrossRefPubMedPubMedCentral

15.

Jia J, Dong J, Deng L (2022) Network meta-analysis of different intravenous glucocorticoid regimes for the treatment of Graves’ orbitopathy. Front Pharmacol 13:1–9. https://doi.org/10.3389/fphar.2022.785757CrossRef

16.

Lendorf ME, Rasmussen ÅK, Fledelius HC, Feldt-Rasmussen U (2009) Cardiovascular and cerebrovascular events in temporal relationship to intravenous glucocorticoid pulse therapy in patients with severe endocrine ophthalmopathy. Thyroid 19:1431–1432. https://doi.org/10.1089/thy.2009.0069CrossRefPubMed

17.

Weissel M, Hauff W (2000) Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient with severe thyroid eye disease. Thyroid 10:521. https://doi.org/10.1089/thy.2000.10.521CrossRefPubMed

18.

Marinól M, Morabito E, Brunetto MR, Bartalena L, Pinchera A, Marocci C (2004) Acute and severe liver damage associated with intravenous glucocorticoid pulse therapy in patients with Graves’ ophthalmopathy. Thyroid 14:403–406. https://doi.org/10.1089/105072504774193276CrossRef

19.

Salvi M, Vannucchi G, Sbrozzi F, Del Castello AB, Carnevali A, Fargion S, Beck-Peccoz P (2004) Onset of autoimmune hepatitis during intravenous steroid therapy for thyroid-associated ophthalmopathy in a patient with Hashimoto’s thyroiditis: case report. Thyroid 14:631–634. https://doi.org/10.1089/1050725041692927CrossRefPubMed

20.

Marinò M, Morabito E, Altea MA, Ambrogini E, Oliveri F, Brunetto MR, Pollina LE, Campani D, Vitti P, Bartalena L (2005) Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves’ ophthalmopathy treated successfully with glucocorticoids themselves. J Endocrinol Invest 28:280–284. https://doi.org/10.1007/BF03345386CrossRefPubMed

21.

Le Moli R, Baldeschi L, Saeed P, Regensburg N, Mourits MP, Wiersinga WM (2007) Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves’ ophthalmopathy. Thyroid 17:357–362. https://doi.org/10.1089/thy.2006.0267CrossRefPubMed

22.

Gursoy A, Cesur M, Erdogan MF, Çorapcioglu D, Kamel N (2006) New-onset acute heart failure after intravenous glucocorticoid pulse therapy in a patient with Graves’ ophthalmopathy. Endocrine 29:513–516. https://doi.org/10.1385/ENDO:29:3:513CrossRefPubMed

23.

Owecki M, Sowiński J (2006) Acute myocardial infarction during high-dose methylprednisolone therapy for Graves’ ophthalmopathy. Pharm World Sci 28:73–75. https://doi.org/10.1007/s11096-006-9013-yCrossRefPubMed

24.

Zang S, Ponto KA, Kahaly GJ (2011) Intravenous glucocorticoids for Graves’ orbitopathy: efficacy and morbidity. J Clin Endocrinol Metab 96:320–332. https://doi.org/10.1210/jc.2010-1962CrossRefPubMed

25.

He Y, Mu K, Liu R, Zhang J, Xiang N (2017) Comparison of two different regimens of intravenous methylprednisolone for patients with moderate to severe and active Graves’ ophthalmopathy: a prospective, randomized controlled trial. Endocr J 64:141–149. https://doi.org/10.1507/endocrj.EJ16-0083CrossRefPubMed

26.

Bartalena L, Veronesi G, Krassas GE, Wiersinga WM, Marcocci C, Marinò M, Salvi M, Daumerie C, Bournaud C, Stahl M et al (2017) Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves’ orbitopathy? J Endocrinol Invest 40:547–553. https://doi.org/10.1007/s40618-017-0608-zCrossRefPubMed

27.

Zangi S, Ponto KA, Pitz S, Kahaly GJ (2011) Dose of intravenous steroids and therapy outcome in Graves’ orbitopathy. J Endocrinol Invest 34:876–880. https://doi.org/10.1007/BF03346732CrossRef

28.

Hoppe E, Lee ACH, Hoppe D, Kahaly GJ (2021) Predictive factors for changes in quality of life after steroid treatment for active moderate-to-severe Graves’ orbitopathy: a prospective trial. Eur Thyroid J 9:313–320. https://doi.org/10.1159/000508071CrossRefPubMed

29.

Tsirouki T, Bargiota A, Tigas S, Vasileiou A, Kapsalaki E, Giotaki Z, Asproudis I, Tsatsoulis A, Koukoulis G, Tsironi EE (2016) Clinical and imaging evaluation of the response to intravenous steroids in patients with Graves’ orbitopathy and analysis on who requires additional therapy. Clin Opthalmol 10:2277–2289. https://doi.org/10.2147/OPTH.S118555CrossRef

Title: Comparison of the efficacy of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves’ orbitopathy
Authors: Mariya Asenova Stoynova
Alexander Dimitrov Shinkov
Inna Dimitrova Dimitrova
Inna Angelova Yankova
Roussanka Dimitrova Kovatcheva
Publication date: 12-09-2023
Publisher: Springer Netherlands
Keyword: Glucocorticoid
Published in: International Ophthalmology / Issue 12/2023
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-023-02875-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Comparison of the efficacy of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves’ orbitopathy

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2023

Analysis of the capsular bend in posterior capsular opacification using anterior segment optical coherence tomography

Evaluation of recovery time of tear film function and ocular surface after discontinuing oral isotretinoin treatment for acne vulgaris

Assessment of retinal and choroidal vessel density and nerve fibre layer thickness changes after orbitotomy in patients with severe non-active thyroid orbitopathy: a prospective study

Horizontal eyelid shortening alone versus combined procedures for the correction of involutional lower eyelid entropion

Therapeutic effect of a new implantation method of rotationally asymmetric multifocal intraocular lenses on visual quality

Does occupational radiation exposure affect retinal nerve fiber thickness?