Comparative efficacy and safety of rituximab, tocilizumab, and teprotumumab in Graves' orbitopathy: a systematic review and meta-analysis.

Graves' orbitopathy (GO) affects 25-50% of patients with Graves' disease. It progresses through phases, from active inflammation to fibrosis. Thyrotropin-related antibodies (TRAb) and Insulin-like growth factor (IGF-1) contribute to GO's pathogenesis. Conventional treatments like glucocorticoids are often effective, but refractory cases require alternatives like rituximab (RTX), tocilizumab (TCZ), and teprotumumab (TPM). These monoclonal antibodies show promise but carry significant risks. This review aims to assess their efficacy and safety. We retrieved relevant articles up to July 2024 from five databases. Data were extracted from eligible studies by two independent reviewers, including clinical activity scores 7 and 10 (CAS), proptosis, antibody levels, and diplopia. All analyses were conducted using RevMan v5.4. In this review, we included 77 articles. Of these, 58 provided enough data for analysis. TPM, RTX, and TCZ all significantly reduced CAS-7 scores, with TCZ showing the most significant reduction (3.51 points, 95%CI: -4.25, -2.78), followed by TPM (3.1 points, 95%CI: -3.71, -2.49) and RTX. Similarly, for CAS-10, TCZ led with a 5.12-point reduction, significantly outperforming RTX (P = 0.0006). Proptosis decreased significantly with each drug, with TPM leading (2.95 mm), followed by TCZ (1.99 mm) and RTX (0.79 mm). TRAb Levels: TCZ reduced TRAb levels by 8.29 U/L (95%CI: -10.48, -6.09), significantly more than RTX (P = 0.03). Complications varied, with TPM linked to hyperglycemia and ototoxicity, TCZ to hematologic and metabolic issues, and RTX to infusion-related reactions. In conclusion, TCZ and TPM outperform RTX in treating GO, but TPM has higher complications, and RTX, though safer, shows more treatment failures.