Incidence of Alemtuzumab-Induced Thyroid-Associated Orbitopathy: A Systematic Review and Meta-Analysis

Purpose: Alemtuzumab is a monoclonal antibody that targets CD52 and is commonly used to treat multiple sclerosis. Thyroid dysfunction occurs in 20% to 30% of patients treated with alemtuzumab. This may lead to thyroid-associated orbitopathy (TAO), which can cause debilitating dry eye, diplopia, proptosis, ocular pain, and vision loss. This meta-analysis aims to quantify the incidence of alemtuzumab-induced TAO (AI-TAO) and to characterize its clinical features. Methods: Studies were extracted from Cochrane, Embase (Ovid), Medline (Ovid), and additional gray literature. Using R version 4.4.1 on RStudio, the meta-analysis was conducted using the meta package. Depending on the level of heterogeneity, either a fixed-effects or random-effects model was used to pool the data. Funnel plots were used to assess publication bias. Results: Meta-analysis of 1545 patients across 12 studies revealed that the incidence of alemtuzumab-induced Graves’ disease was 25% (95% confidence interval [CI]: 11–46%) and AI-TAO was 6% (95% CI: 3–10%). Of the patients with established alemtuzumab-induced Graves’ disease, 20% (95% CI: 12–30%) developed TAO. Pooled analysis of 8 studies (n = 556), revealed that the mean onset of AI-TAO was 37.38 months (95% CI: 28.90–46.76). In summary, 51/65 (78.5%) of TAO patients were managed conservatively, and 22/65 (33.9%) were managed surgically. Orbital decompression was required in only 5/65 (7.7%) patients. Conclusions: The incidence of AI-TAO is 6% which is less common than the estimated incidence of 20% to 30% of alemtuzumab-induced thyroid dysfunction. This finding emphasizes the need for patient counseling, baseline ophthalmic examination, and interdisciplinary follow-up for early detection and management of AI-TAO.