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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Endocrinol.</journal-id>
<journal-title>Frontiers in Endocrinology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Endocrinol.</abbrev-journal-title>
<issn pub-type="epub">1664-2392</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fendo.2024.1394616</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Endocrinology</subject>
<subj-group>
<subject>General Commentary</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Commentary: Efficacy and safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves&#x2019; ophthalmopathy: a systematic review and meta-analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Lingxiao</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Wu</surname>
<given-names>Jihong</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2671451"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/validation/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Department of Critical Care Medicine, Wuwei Liangzhou Hospital</institution>, <addr-line>Wuwei, Gansu</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Endocrinology, Wuwei Liangzhou Hospital</institution>, <addr-line>Wuwei, Gansu</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Ajay Pradhan, AstraZeneca, Sweden</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Danilo Villagelin, Pontifical Catholic University of Campinas, Brazil</p>
<p>Ceyhun Bereketoglu, Marmara University, T&#xfc;rkiye</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Jihong Wu, <email xlink:href="mailto:haokh6273@163.com">haokh6273@163.com</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>28</day>
<month>05</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1394616</elocation-id>
<history>
<date date-type="received">
<day>01</day>
<month>03</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>06</day>
<month>05</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Li and Wu</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Li and Wu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" xlink:href="10.3389/fendo.2023.1160936" ext-link-type="doi">A Commentary on <article-title>Efficacy and safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves&#x2019; ophthalmopathy: a systematic review and meta-analysis</article-title> By Hu Y, Chen J, Lin K and Yu X (2023). <italic>Front. Endocrinol.</italic> 14:1160936. doi:&#xa0;<object-id>10.3389/fendo.2023.1160936</object-id>
</related-article>
<kwd-group>
<kwd>Graves&#x2019; ophthalmopathy</kwd>
<kwd>monoclonal antibodies</kwd>
<kwd>efficacy</kwd>
<kwd>meta-analysis</kwd>
<kwd>comment</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="3"/>
<page-count count="2"/>
<word-count count="485"/>
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<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Experimental Endocrinology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<p>The therapeutic landscape for Graves&#x2019; ophthalmopathy (GO) is undergoing significant change, underscored by the pivotal role of intravenous glucocorticoids (GCs) and the emerging efficacy of monoclonal antibodies (mAbs). We recently read an article published in Frontiers in endocrinology by Hu et&#xa0;al. The study compares the results of rituximab, tocilizumab, and teprotumumab in the treatment of moderate to severe GO, providing a nuanced analysis of their relative efficacy and safety profiles (<xref ref-type="bibr" rid="B1">1</xref>). We congratulate the authors on a very comprehensive work. However, to further improve the quality and readability of the article, we believe there are several points that could enhance the validity of these findings.</p>
<p>First, the methodological rigor of including both randomized controlled trials and observational studies provides a comprehensive view of the therapeutic potential of mAbs. However, the inclusion of observational studies, while expanding the data set, introduces variability that could potentially bias comparative efficacy results. In addition, the reliance on clinical activity score as the primary measure, while standard, may not fully capture the multifaceted outcomes relevant to patient quality of life.</p>
<p>Second, the nuanced analysis comparing rituximab, tocilizumab, and teprotumumab reveals a complex hierarchy of efficacy and tolerability. While monoclonal antibodies are ushering in a new era of GO treatment, their diverse targets and mechanisms present a labyrinthine picture of therapeutic choices. The differential effects of tocilizumab and teprotumumab on proptosis and diplopia, contrasted with the variable performance of rituximab, underscore the need for personalized treatment strategies tailored to individual patient profiles and disease manifestations.</p>
<p>Third, the discussion of safety profiles is paramount, especially in light of the serious concerns surrounding high-dose GC therapy. The mild to moderate adverse events associated with mAbs, contrasted with the severe, sometimes fatal, hepatotoxicity associated with GCs, is driving a shift toward these novel agents. However, the potential for serious complications, such as opportunistic infections with tocilizumab (<xref ref-type="bibr" rid="B2">2</xref>), requires vigilant monitoring and judicious clinical decision-making.</p>
<p>Fourth, the search for optimal dosing and a deeper understanding of the mechanisms of action of mAbs remains unfulfilled. This gap highlights the urgent need for further research, including mechanistic studies and tailored therapeutic regimens (<xref ref-type="bibr" rid="B3">3</xref>). In addition, the exploration of mAbs in the treatment of GO promises to reevaluate treatment paradigms and potentially revolutionize patient care for this debilitating disease.</p>
<p>Finally, the comparative analysis of monoclonal antibodies in the treatment of GO opens new avenues for intervention, promising improved efficacy with a more favorable safety profile than traditional glucocorticoids. However, the path from empirical evidence to clinical practice is fraught with unanswered questions and the need for meticulous patient-centered research. As we stand on the cusp of therapeutic innovation, the integration of mAbs into the GO treatment armamentarium must be approached with caution, recognizing the diversity of patient responses and the complexity of autoimmune pathogenesis.</p>
<sec id="s1" sec-type="author-contributions">
<title>Author contributions</title>
<p>LL: Formal analysis, Investigation, Writing &#x2013; original draft. JW: Conceptualization, Methodology, Supervision, Validation, Visualization, Writing &#x2013; review &amp; editing.</p>
</sec>
</body>
<back>
<sec id="s2" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<sec id="s3" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s4" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="B1">
<label>1</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hu</surname> <given-names>Y</given-names>
</name>
<name>
<surname>Chen</surname> <given-names>J</given-names>
</name>
<name>
<surname>Lin</surname> <given-names>K</given-names>
</name>
<name>
<surname>Yu</surname> <given-names>X</given-names>
</name>
</person-group>. <article-title>Efficacy and Safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves&#x2019; ophthalmopathy: a systematic review and meta-analysis</article-title>. <source>Front Endocrinol (Lausanne)</source>. (<year>2023</year>) <volume>14</volume>:<elocation-id>1160936</elocation-id>. doi:&#xa0;<pub-id pub-id-type="doi">10.3389/fendo.2023.1160936</pub-id>
</citation>
</ref>
<ref id="B2">
<label>2</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Devauchelle-Pensec</surname> <given-names>V</given-names>
</name>
<name>
<surname>Carvajal-Alegria</surname> <given-names>G</given-names>
</name>
<name>
<surname>Dernis</surname> <given-names>E</given-names>
</name>
<name>
<surname>Richez</surname> <given-names>C</given-names>
</name>
<name>
<surname>Truchetet</surname> <given-names>ME</given-names>
</name>
<name>
<surname>Wendling</surname> <given-names>D</given-names>
</name>
<etal/>
</person-group>. <article-title>Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial</article-title>. <source>JAMA</source>. (<year>2022</year>) <volume>328</volume>(<issue>11</issue>):<page-range>1053&#x2013;62</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.1001/jama.2022.15459</pub-id>
</citation>
</ref>
<ref id="B3">
<label>3</label>
<citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname>Fatani</surname> <given-names>WA</given-names>
</name>
<name>
<surname>Hamdan</surname> <given-names>DM</given-names>
</name>
<name>
<surname>Taher</surname> <given-names>NO</given-names>
</name>
<name>
<surname>Alsharef</surname> <given-names>JF</given-names>
</name>
<name>
<surname>Aldubi</surname> <given-names>RM</given-names>
</name>
<name>
<surname>Alwagdani</surname> <given-names>AM</given-names>
</name>
<etal/>
</person-group>. <article-title>Monoclonal antibodies for the treatment of Graves' ophthalmopathy: A systematic review and meta-analysis</article-title>. <source>Saudi J Ophthalmol</source>. (<year>2023</year>) <volume>37</volume>(<issue>2</issue>):<page-range>137&#x2013;48</page-range>. doi:&#xa0;<pub-id pub-id-type="doi">10.4103/sjopt.sjopt_176_22</pub-id>
</citation>
</ref>
</ref-list>
</back>
</article>