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. 2023 May 2;37(2):137-148.
doi: 10.4103/sjopt.sjopt_176_22. eCollection 2023 Apr-Jun.

Monoclonal antibodies for the treatment of Graves' ophthalmopathy: A systematic review and meta-analysis

Wed A Fatani  1   2 , Dalia M Hamdan  1   2 , Nada O Taher  1   2 , Jawaher F Alsharef  1   2 , Riyam M Aldubi  1   2 , Alhanouf M Alwagdani  1   2 , Taif N Alhothali  3 , Zia U Khan  2   4   5
Affiliations

Monoclonal antibodies for the treatment of Graves' ophthalmopathy: A systematic review and meta-analysis

Wed A Fatani et al. Saudi J Ophthalmol. .

Abstract

Purpose: The traditional standard of care for Graves' 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]).

Methods: 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.

Results: Six (n = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid/placebo in terms of reduction in CAS (SMD = -1.44, 95% confidence interval (CI): -1.91--0.97, P < 0.00001, I2 = 74%), change in proptosis (SMD = -4.96, 95% CI: -8.02--1.89, P = 0.002, I2 = 99%), QoL (SMD = 2.64, 95% CI: 0.50-4.79, P = 0.02, I2 = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62-7.22, P = 0.001, I2 = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12-7.56, P = 0.03, I2 = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels.

Conclusion: 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.

Keywords: Graves’; ophthalmopathy; orbitopathy; rituximab; teprotumumab; thyroid eye disease; tocilizumab.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Study flow diagram. RCT: Randomized controlled trial
Figure 2
Figure 2
Risk-of-bias graph
Figure 3
Figure 3
Risk-of-bias summary
Figure 4
Figure 4
Clinical activity score. (a) Forest plot. (b) Funnel plot. CI: Confidence interval, IV: Inverse variance, RTX: Rituximab
Figure 5
Figure 5
Change in proptosis. (a) Forest plot. (b) Funnel plot.
Figure 6
Figure 6
Gorman diplopia score. (a) Forest plot. (b) Funnel plot
Figure 7
Figure 7
Change in lid fissure. (a) Forest plot. (b) Funnel plot
Figure 8
Figure 8
Adverse events. (a) Forest plot. (b) Funnel plot
Figure 9
Figure 9
NOSPECS score. (a) Forest plot. (b) Funnel plot
Figure 10
Figure 10
Quality of life. (a) Forest plot. (b) Funnel plot
Figure 11
Figure 11
TRAb. (a) Forest plot. (b) Funnel plot. TRAb: TSH receptor antibody
See this image and copyright information in PMC

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