{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:36:45Z","timestamp":1787773005001,"version":"build-2784847793"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"\n PURPOSE:<\/jats:title>\n The traditional standard of care for Graves\u2019 ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this systematic review and meta-analysis was to compare the traditional therapy to novel monoclonal antibodies (e.g. rituximab [RTX], teprotumumab, and tocilizumab [TCZ]).<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials (RCTs) that compared different monoclonal antibodies (e.g. RTX, teprotumumab, and TCZ) with glucocorticoids or placebo in patients with GO. We evaluated the clinical activity score (CAS), proptosis, subjective diplopia using the Gorman score, quality of life (QoT), adverse events, change in lid fissure, NOSPECS score, and TSH receptor antibody (TRAb) levels. The odds ratio (OR) was used to represent dichotomous outcomes. The continuous outcomes were represented as standardized mean difference (SMD). Data were pooled using the inverse variance weighting method. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Six (\n n<\/jats:italic>\n = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid\/placebo in terms of reduction in CAS (SMD = \u22121.44, 95% confidence interval (CI): \u22121.91\u2013\u22120.97,\n P<\/jats:italic>\n < 0.00001,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 74%), change in proptosis (SMD = \u22124.96, 95% CI: \u22128.02\u2013\u22121.89,\n P<\/jats:italic>\n = 0.002,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 99%), QoL (SMD = 2.64, 95% CI: 0.50\u20134.79,\n P<\/jats:italic>\n = 0.02,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62\u20137.22,\n P<\/jats:italic>\n = 0.001,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12\u20137.56,\n P<\/jats:italic>\n = 0.03,\n I<\/jats:italic>\n 2<\/jats:sup>\n = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION:<\/jats:title>\n This meta-analysis demonstrated that monoclonal antibodies were associated with more favorable clinical outcomes than standard steroid therapy or placebo, especially with regard to CAS, change in proptosis, diplopia, and QoL, with teprotumumab being superior. In addition, only minor safety concerns were identified with monoclonal antibodies though less worrisome than using traditional steroids.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/sjopt.sjopt_176_22","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T07:09:34Z","timestamp":1725001774000},"page":"137-148","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Monoclonal antibodies for the treatment of Graves\u2019 ophthalmopathy: A systematic review and meta-analysis"],"prefix":"10.4103","volume":"37","author":[{"given":"Wed A.","family":"Fatani","sequence":"first","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia M.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada O.","family":"Taher","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawaher F.","family":"Alsharef","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyam M.","family":"Aldubi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alhanouf M.","family":"Alwagdani","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taif N.","family":"Alhothali","sequence":"additional","affiliation":[{"name":"College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zia U.","family":"Khan","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah, Saudi Arabia"},{"name":"Department of Ophthalmology, King Abdulaziz Medical City, Jeddah, Saudi Arabia"},{"name":"Department of Ophthalmology, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"R1-20240830","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1056\/NEJMoa1910434","article-title":"Teprotumumab for the treatment of active thyroid eye disease","volume":"382","author":"Douglas","year":"2020","journal-title":"N Engl J Med"},{"key":"R2-20240830","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1038\/s41433-021-01593-z","article-title":"Teprotumumab for the treatment of chronic thyroid eye disease","volume":"36","author":"Ugradar","year":"2022","journal-title":"Eye (Lond)"},{"key":"R3-20240830","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000453618","article-title":"The efficacy of rituximab combined with 131i for ophthalmic outcomes of graves'ophthalmopathy patients","volume":"99","author":"Li","year":"2017","journal-title":"Pharmacology"},{"key":"R4-20240830","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1210\/jc.2014-3014","article-title":"Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves'orbitopathy:A randomized controlled study","volume":"100","author":"Salvi","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"R5-20240830","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/WNO.0000000000000132","article-title":"The pathophysiology of thyroid eye disease","volume":"34","author":"Shan","year":"2014","journal-title":"J Neuroophthalmol"},{"key":"R6-20240830","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4236\/ojemd.2017.71008","article-title":"Pathophysiology of graves'ophthalmopathy:A literature review","volume":"7","author":"Carballo","year":"2017","journal-title":"Open J Endocr Metab Dis"},{"key":"R8-20240830","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1007\/s13346-020-00843-z","article-title":"Corticosteroids in ophthalmology:Drug delivery innovations, pharmacology, clinical applications, and future perspectives","volume":"11","author":"Gaballa","year":"2021","journal-title":"Drug Deliv Transl Res"},{"key":"R9-20240830","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/phar.2111","article-title":"Efficacy and safety of rituximab for the treatment of graves'orbitopathy:A meta-analysis of randomized controlled trials","volume":"38","author":"Shen","year":"2018","journal-title":"Pharmacotherapy"},{"key":"R10-20240830","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1056\/NEJMoa1614949","article-title":"Teprotumumab for thyroid-associated ophthalmopathy","volume":"376","author":"Smith","year":"2017","journal-title":"N Engl J Med"},{"key":"R11-20240830","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions:explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"R12-20240830","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1210\/jc.2014-2572","article-title":"Randomized controlled trial of rituximab in patients with graves'orbitopathy","volume":"100","author":"Stan","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"R13-20240830","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ajo.2018.07.038","article-title":"Efficacy of tocilizumab in patients with moderate-to-severe corticosteroid-resistant graves orbitopathy:A randomized clinical trial","volume":"195","author":"Perez-Moreiras","year":"2018","journal-title":"Am J Ophthalmol"},{"key":"R14-20240830","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1530\/eje.1.02119","article-title":"Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression","volume":"154","author":"Salvi","year":"2006","journal-title":"Eur J Endocrinol"},{"key":"R15-20240830","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fonc.2018.00163","article-title":"Past, present, and future of rituximab-the world's first oncology monoclonal antibody Therapy","volume":"8","author":"Pierpont","year":"2018","journal-title":"Front Oncol"},{"key":"R16-20240830","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41433-018-0315-9","article-title":"Interruption of autoimmunity for thyroid eye disease:B-cell and T-cell strategy","volume":"33","author":"Strianese","year":"2019","journal-title":"Eye (Lond)"},{"key":"R17-20240830","doi-asserted-by":"crossref","first-page":"249125","DOI":"10.1155\/2015\/249125","article-title":"Graves'ophthalmopathy:VISA versus EUGOGO classification, assessment, and management","volume":"2015","author":"Barrio-Barrio","year":"2015","journal-title":"J Ophthalmol"},{"key":"R18-20240830","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12886-018-0679-4","article-title":"Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy?A systematic review and meta-analysis","volume":"18","author":"Wang","year":"2018","journal-title":"BMC Ophthalmol"},{"key":"R19-20240830","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1530\/eje.1.02325","article-title":"Treatment of graves'disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab:An open study","volume":"156","author":"Salvi","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"R20-20240830","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1097\/IOP.0000000000001959","article-title":"Early experience with the clinical use of teprotumumab in a heterogenous thyroid eye disease population","volume":"37","author":"Diniz","year":"2021","journal-title":"Ophthalmic Plast Reconstr Surg"},{"key":"R21-20240830","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3390\/jcm10040706","article-title":"Steroid-resistant graves'orbitopathy treated with tocilizumab in real-world clinical practice:A 9-year single-center experience","volume":"10","author":"P\u00e9rez-Moreiras","year":"2021","journal-title":"J Clin Med"},{"key":"R22-20240830","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1097\/IOP.0000000000000730","article-title":"Clinical response to tocilizumab in severe thyroid eye disease","volume":"33","author":"Sy","year":"2017","journal-title":"Ophthalmic Plast Reconstr Surg"},{"key":"R23-20240830","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1001\/jamaophthalmol.2021.6284","article-title":"Proptosis and diplopia response with teprotumumab and placebo versus the recommended treatment regimen with intravenous methylprednisolone in moderate to severe thyroid eye disease:A meta-analysis and matching-adjusted indirect comparison","volume":"140","author":"Douglas","year":"2022","journal-title":"JAMA Ophthalmol"},{"key":"R24-20240830","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1080\/01676830.2021.1933081","article-title":"Teprotumumab for chronic thyroid eye disease","volume":"41","author":"Ozzello","year":"2022","journal-title":"Orbit"},{"key":"R25-20240830","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1177\/1120672119845224","article-title":"The effects of rituximab on graves'orbitopathy:A retrospective study of 14 patients","volume":"30","author":"Eid","year":"2020","journal-title":"Eur J Ophthalmol"},{"key":"R26-20240830","doi-asserted-by":"crossref","first-page":"100744","DOI":"10.1016\/j.ajoc.2020.100744","article-title":"Early experience with teprotumumab for chronic thyroid eye disease","volume":"19","author":"Ozzello","year":"2020","journal-title":"Am J Ophthalmol Case Rep"},{"key":"R27-20240830","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajo.2022.02.015","article-title":"Hearing dysfunction after treatment with teprotumumab for thyroid eye disease","volume":"240","author":"Sears","year":"2022","journal-title":"Am J Ophthalmol"},{"key":"R28-20240830","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jcjo.2020.07.020","article-title":"Treatment of corticosteroid-resistant thyroid eye disease with subcutaneous tocilizumab","volume":"56","author":"Silkiss","year":"2021","journal-title":"Can J Ophthalmol"},{"key":"R29-20240830","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13044-020-00086-7","article-title":"Teprotumumab:A disease modifying treatment for graves'orbitopathy","volume":"13","author":"Ting","year":"2020","journal-title":"Thyroid Res"},{"key":"R30-20240830","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.ophtha.2021.10.017","article-title":"Teprotumumab efficacy, safety, and durability in longer-duration thyroid eye disease and re-treatment:OPTIC-X study","volume":"129","author":"Douglas","year":"2022","journal-title":"Ophthalmology"}],"container-title":["Saudi Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/sjopt.sjopt_176_22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:15:45Z","timestamp":1787771745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/sjopt.sjopt_176_22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.4103\/sjopt.sjopt_176_22","relation":{},"ISSN":["1319-4534","2542-6680"],"issn-type":[{"value":"1319-4534","type":"print"},{"value":"2542-6680","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"2022-10-10","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-05","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}