Analysis Of Factors Influencing The Treatment Efficacy In Thyroid Associated Ophthalmopathy

Backgrouds:Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease that occurs predominantly in patients with Graves'disease.Active moderate-to-severe cases required timely treatment and weekly protocol of 4.5g intravenous glucocorticoid(GC)is currently recommended as the first-line therapy,but they are not always effective.It is also difficult to accurately assess the patient's activity in clinical assessment.Objective:The aim of this study is to assess predictors of GC response and investigate new treatment in TAO.This study is not only help to clarify the reasons for the ineffectiveness of GC therapy,but also opens doors toward individualized treatment of TAO.Methods:1.Sixty-six individuals with active moderate-to-severe GO who were treated with weekly protocol of 4.5 g intravenous methylprednisolone within 3 months were recruited.The patients were grouped as responders and non-responders.Using conditional logistic regression,the odds ratios of responding to GC therapy were assessed.We also combined CAS and baseline MRI to investigate whether these two patameters could predict the response to immunosuppression in TAO patients.2.We conducted a prospective,randomized trial to compare the efficacy and safety of two protocols in a total of 51 active moderate-to-severe TAO patients in our institute.Patients were randomly assigned to receive intravenous methylprednisolone either alone or with methotrexate3.293 T cell line was transfected with NF-?B luciferase vectors and cultured in the presence of dexamethasone or with methotrexate.The repression rate of NF-?B transcriptional activity was evaluated in vitro highly inflamed circumstancesResults:1.Smoking(OR 7.027,95%CI 1.528 to 32.304,p=0.012)and GO duration(OR 14.662,95%CI 2.662 to 80.782,p=0.002)were associated with high risks of poor intravenous GC response.In long-course TAO patients,non-responders tended to have a significantly lower SIR value of medial rectus(P=0.004)than responders.A multi-variables prediction model(including CAS,TAO duration and SIR value of medial rectus)was established in each quartile as well,which was better than CAS in the forecasting aspect.AUC was increased with each quartile increased(AUCQ2=0.807,PQ2=0.013;AUCQ3=0.813,PQ3=0.009;AUCQ4=0.964,PQ4<0.001)and PPV(92.86%)and NPV(90%)of the prediction model were the highest in the top quartile2.No significant difference was observed in the rate of response at 12 weeks between the GC group and the combined group.The combined group had a higher CAS response(76%)than GC group(53.8%)without statistical significance.The adverse event profile was acceptable without any severe events related to methotrexate3.Methotrexate with dexamethasone synergistically inhibited the transcriptional activity of NF-?B(p=0.002),with an repression rate of 25%,higher than the dexamethasone(10%)or methotrexate(8%)aloneConclusion:Smoking TAO patients with long disease duration may need other optimised treatment strategies.In patients with short duration of symptoms,CAS?3 alone indicated a good time for treatment,however,the combination of CAS and MRI is most suitable for predicting immunosuppression response in long-course TAO patients.Although GC combined with methotrexate was not significantly better than GC alone in clinical practice,but methotrexate can synergize with dexamethasone to enhance partial immunosuppression at the cellular level,which suggested that the combined group can be used for TAO patients with poor GC efficacy.