Abstract
Purpose Numerous medical strategies have been proposed for the treatment of thyroid eye disease (TED); however, the best methods for standard treatment are still a matter of controversy. The purpose of this network meta-analysis was to integrate previous evidence to create hierarchies of comparative efficacy of eleven commonly used medical treatments for TED. Methods A comprehensive search of electronic scientific literature databases was performed and the data from randomized controlled trials (RCTs) comparing treatment outcomes for patients with active TED were selected. Treatment strategies included in this network meta-analysis were intravenous glucocorticoids (IVGC), oral glucocorticoids (OGC), orbital injection of glucocorticoids (OIGC), orbital radiotherapy (OR), intravenous glucocorticoids combined with orbital radiotherapy (IVGC + OR), oral glucocorticoids combined with orbital radiotherapy (OGC + OR), rituximab (RTX), somatostatin analogs, intravenous immunoglobulin (IVIG), teprotumumab, and cyclosporine. The outcomes were response rate, mean difference in proptosis reduction, and reduction in disease activity. A random-effects network meta-analysis using a frequent method was conducted in STATA. Results Twenty-three studies comprising a total of 1047 patients were included in the analysis. Inconsistency plots showed heterogeneity in the IVGC-Placebo-RTX loop to some extent (RoR = 8.029, P=0.075). Rankings of response rates were as follows: IVGC + OR, teprotumumab, IVGC, OGC + OR, RTX, OIGC, OR, IVIG, OGC, somatostatin, placebo, and cyclosporine. The rank probability analysis of proptosis reduction showed that teprotumumab was the most effective, followed by IVGC, IVGC + OR, OIGC, OGC, OGC + OR, OR, somatostatin, cyclosporine, and placebo. Conclusions IVGC, alone or combination with OR, and teprotumumab should be preferred as the most effective strategies for active moderate to severe TED. Teprotumumab showed profound effect on proptosis reduction. OIGC, OR, and somatostatin analogs showed some statistical benefit and can be employed as second-line treatment strategies. RTX is a promising biologic agent, but more RCTs are required to define its appropriate role in treating TED.
Highlights
Epidemiological studies have revealed that the majority of thyroid eye disease (TED) patients have stable and mild eye sign, but approximately 3%–6% of TED patients progress to an active moderate-to-severe phase with intense orbital pain, inflammation, motility restriction, and even sightthreatening corneal ulceration or compressive optic neuropathy [1, 2]
All articles comparing any treatment strategy with a placebo or another strategy for the treatment of active TED were recruited. e trials enrolled in the network meta-analysis meet the following criteria: the study design was randomized controlled trials (RCTs); participants had active TED; efficacy outcomes included response rate, proptosis, and disease activity
We merged sham radiation and placebo groups from each study into a placebo group, a total of eleven different medical treatment strategies and placebo were identified, including intravenous glucocorticoids (IVGC) [10,11,12,13,14,15], oral glucocorticoids (OGC) [10, 12, 14,15,16,17,18,19,20,21], orbital injection of glucocorticoids (OIGC) [16], orbital radiotherapy (OR) [22, 23], IVGC combined with OR (IVGC + OR) [13, 24], OGC combined with OR (OGC + OR) [21, 24, 25], rituximab (RTX) [26, 27], somatostatin analogs [28,29,30,31], intravenous immunoglobulin (IVIG) [18], teprotumumab [4], and cyclosporine [20]
Summary
E trials enrolled in the network meta-analysis meet the following criteria: the study design was RCT; participants had active TED; efficacy outcomes included response rate, proptosis, and disease activity. Trials were excluded as follows: treatment strategies for patients with hyperthyroidism; surgical treatment for TED; study outcomes not containing response rate; duplicated publications. Two investigators (NX and YC) selected studies and extracted the data from each included trial independently. E risk of bias includes seven components: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. A network plot was employed to represent the overall information of the trials included in the analysis. When the 95% CIs of an RoR value reached one, no statistical inconsistency was considered to exist for this trial. Treatment strategies with a greater value in the histogram were associated with a greater probability of superior efficacy
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