Table 1.
Current and potential treatment for Graves’ ophthalmopathy (GO).
|
Therapy, FDA Approved
[Reference] |
Mechanism | Study Design | Disease Status | Outcome | Adverse Effect |
| Teprotumumab [2] | Monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R) | RCT (n = 41) iv 10 mg/kg initially, followed by 20 mg/kg in 3 weeks for 7 additional infusions |
Moderate to severe | Improved QOL and proptosis Improvement (83% vs. 10% p < 0.001) after 24 weeks |
(1) Hyperlipidemia (2) Hearing impairment |
| Therapeutic agents with RCT [reference] | Mechanism | Study design | Disease Status | Outcome | Adverse effect |
| Rituximab [77] | Monoclonal antibody against CD20 | RCT (n = 31) iv 2000 mg or 500 mg control: iv methylprednisolone |
Moderate to severe | Better ocular motility and QOL after 24 weeks | (1) Infusion reaction (2) Transient hypotension |
| [78] | RCT (n = 13) iv 1000 mg twice in 2 weeks control: placebo |
Moderate to severe | No benefit | Infectious bronchitis, conjunctivitis, vasculitis, optic neuropathy, gastrointestinal disorder | |
| Selenium [85] | Antioxidant | RCT (n = 54) 200 μg/day for 6 months |
Mild | Improved QOL and ocular sign, decreased progression | (−) |
| Pentoxifylline [85] | Antioxidant | RCT (n = 48) 1200 mg/day for 6 months |
Mild | No benefit | Mild gastrointestinal and skin disorders |
| [95] | RCT (n = 9) 1200 mg/day for 6 months |
Inactive | QOL and proptosis improvement | Mild gastrointestinal disorder | |
| Nicotinamide and Allopurinol [100] |
Antioxidant | Nonrandomized comparative study (n = 11) Oral allopurinol (300 mg/day) and nicotinamide (300 mg/day) for 3 months |
Mild to moderate |
Improved soft tissue inflammation | (−) |
|
Potential therapeutic agents without RCT
[reference] |
Mechanism | ||||
| Tasquinimod [60] | Inhibitor of histone deacetylases 4 (HDAC4), which decreased the mRNA expression of hyaluronan synthase | ||||
| Tocilizumab [79] | Monoclonal interleukin-6 receptor antagonist | ||||
| Pirfenidone [102,103,104,105] | (1) Decreased inflammation by attenuation of COX-2, prostaglandin E2 (2) Decreased ECM production |
||||
| CD40Apt [106] | Specific binding affinity to CD40 represents a promising inhibitor of the CD40-CD40L signaling | ||||
| Potential therapeutic targets [reference] | Mechanism | ||||
| Antagonist of peroxisome proliferator-activated receptor γ (PPARγ) [10,11,12] | Inhibition of adipogenesis | ||||
| Antagonist of transforming growth factor-β1 (TGF-β1) downstream [22,23,24,25] | Inhibition of TGF-β-Induced myofibroblast transdifferentiation in orbital fibroblasts and ECM production | ||||
| Antagonist of thioredoxin domain-containing 5 (TXNDC5) [our study, not published] | Reduction in ER stress and tissue remodeling | ||||
| Non-coding RNA [61,62,63,64,65,66,67,68,69,70,71,72] | Decreased levels of mi146a: decreased inflammation, decreased fibrosis in GO Increased levels of mi155: decreased fibrosis in GO others (miR-29, miR-21, MiR-27a, miR-27b, miR-130a, circRNA, LncRNA) |
||||
FDA: Food and Drug Administration; RCT: randomized control trial; iv: intravenous; QOL: quality of life; ECM: extracellular matrix; COX-2: cyclooxygenase 2; miRNA: microRNA; circRNA: circular RNA; lncRNA: long non-coding RNA.