Efficacy and Safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves’ophthalmopathy: a systematic review and meta-analysis

Abstract

BackgroundsThe effects of various treatments on Graves’ ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs.MethodsTo identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses.ResultsA total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB.ConclusionsBased on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27).Systematic Review Registrationhttp://www.crd.york.ac.uk/prospero, identifier CRD42023398170.

Efficiency and Safety of Tocilizumab for the Treatment of Thyroid Eye Disease: A Systematic Review

“…33,44–49 While the sole randomized controlled trial (RCT) available showed that the reduction in proptosis wasn´t statistically significant at the 40-week follow-up, 44 a recent meta-analysis suggests that TCZ may be the best treatment for proptosis reduction, followed by Teprotumumab and Rituximab. 62 Importantly, considering the 146 patients in which a possible recurrence is described, only 12 presented relapsing signs after treatment discontinuation, 30,32,39,49,54,55,58 which equals an overall relapsing rate of 8.2%, not far from the 7.4% described by Pérez-Moreiras et al 49 in his retrospective analysis of 54 patients.…”

“…Moreover, in the study by Pampín-Sánchez et al, 55 diplopia resolution was only observed in 3 of the 8 affected patients. Hu et al 62 , considering their recent meta-analysis, suggested that TCZ was not optimal for diplopia improvement.…”

Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

“…Diplopia persisted in fewer patients (25%, p = 0.250) after TCZ treatment [ 112 ]. A meta-analysis published in 2023, which analyzed 12 trials with 488 patients, confirmed the high treatment response rate of TCZ, including proptosis reduction (with a better outcome than TPT) [ 113 ]. An ongoing multicenter trial aims to evaluate the efficacy of TED treatment with intravenous TCZ compared to IVGCs (EudraCT number: 2018-002790-22, (accessed on 1 November 2023) identifier: NCT04876534).…”

“…To date, there are no studies on the efficacy of this agent in the treatment of TED. Tocilizumab (TCZ) [113] Anti-IL-6R MAB A total of 12 trials with 448 patients were included Metaanalysis TCZ was most likely to be the best treatment in terms of response and proptosis reduction, followed by TMB and RTX. TMB was most likely to be the best treatment in terms of improving diplopia, followed by TCZ and RTX.…”

Commentary: Efficacy and safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves’ ophthalmopathy: a systematic review and meta-analysis

“…We recently read an article published in Frontiers in endocrinology by Hu et 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 ( 1 ). We congratulate the authors on a very comprehensive work.…”