Clinical Application And Effect Analysis Of Immunomodulatory Drugs In Patients With Graves' Disease

Objective: To investigate the clinical application of immunomodulatory drugs in patients with Graves' disease(GD).To evaluate the therapeutic effect of adjuvant treatment with immunomodulator in patients with primary Graves' disease.To evaluate the efficacy of selenium combined with antithyroid drugs(ATD)in patients with Graves' disease.Methods: 1.Medication statistics: the drug therapy schemes of outpatients with Graves' disease in the department of endocrinology,the first affiliated hospital of China Medical University from January 1,2017 to May 30,2017.The application of immunomodulatory drugs was statistically analyzed by Excel.2.Cohort study: outpatients with primary Graves' disease in the department of endocrinology,the first affiliated hospital of China Medical University from June 1,2016 to December 31,2017 were collected.The remission rates of Graves' disease,serum free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),thyrotrophic hormone receptor antibody(TRAb)levels and the incidences of adverse reactions to liver dysfunction,leukopenia and abnormal neutrophil reduction for 3,6,9,12 months were compared.And the differences in efficacy among the three immunomodulators with more applications were compared.SPSS 20.0 software was used to process data analysis.3.Systematic Review: searching randomized controlled trials(RCTs)from Pubmed,Medline,Cochrane Library,Embase,Web of Science,CNKI,CBM and Wanfang database from inception up to June 2018,we collected the RCTs according to the inclusion and exclusion criteria.Review Manager 5.0 software and Stata 12.0 software was used to process data analysis.Results: 1.Medication statistics: a total of 761 patients with Graves' disease were collected,among which 36.01% and 63.99% were treated with immunoregulatory drugs and basic treatment,respectively.A total of 274 patients with Graves' disease were treated with immunoregulatory drugs.The patients treated with lentinan,pidotimod,transfer factor,Yunzhijun capsules,mannatide and selenium yeast accounted for 44.29%,18.75%,3.26%,12.23%,16.03% and 5.43%,respectively.A total of 126 patients with primary Graves' diseases,among which 39.68% and 60.32% were treated with immunomodulatory drugs and basic treatment,respectively.A total of 635 patients with non-primary Graves' disease,and the patients treated with immunomodulatory drugs and basic treatment accounted for 35.28% and 64.72%,respectively.2.Cohort study: a total of 281 patients with Graves' disease were included,123 patients in the immunomodulator group and 158 patients in the basic treatment group,respectively.The remission rates after 3,6,9 and 12 months in the immunomodulator group were 45.5%,82.8%,93.5% and 97.0%,respectively,while in the basic treatment group were 25.3%,53.4%,75.0% and 83.6%,respectively.After 3,6,9 and 12 months,serum FT3 and FT4 levels in the immunomodulator group were significantly lower than those in the basic treatment group(P<0.05),TSH levels were significantly higher than those in the basic treatment group(P<0.05),and TRAb levels were significantly lower than those in the basic treatment group(P<0.05),and the differences were statistically significant.The three most widely used immunomodulators were lentinan,pidotimod and mannatide,and there was no statistically significant differences in serum FT3,FT4,TSH and TRAb levels among the three groups after 3,6,9 and 12 months.3.Systematic Review: 9 RCTs were included.The result of meta-analysis showed that the levels of serum FT3 and FT4 in selenium supplemental treatment group were significantly decreased than the control group [WMD =-1.48,95% CI(-1.93,-1.02);WMD =-4.89,95% CI(-7.22,-2.56),respectively],while TSH was significantly increased than the control group[WMD = 0.57,95% CI(0.29,0.86)].The levels of thyroid autoantibodys as TPOAb,TGAb,TRAb and immunoglobulin IgA,IgG in selenium supplemental treatment group were significantly lower than the control group,while no significant difference was showed between the two groups in the level of IgM.Conclusion: 1.Medication statistics: More than one-third of Graves' patients received adjuvant treatment with immunomodulatory drugs.Among the immunomodulatory drugs,lentinan was the most frequently used,followed by pidotimod,mannatide,Yunzhijun capsules,selenium yeast and transfer factor.The proportion of patients with primary Graves' disease receiving immunomodulatory drug adjuvant treatment was higher than that of non-primary patients.2.Cohort study: Using immunomodulator adjuvant treatment was more beneficial in patients with primary Graves' disease compared with basic treatment and could significantly increase the remission rates,dcrease the serum FT3,FT4,TRAb levels and increase the serum TSH level,and significantly reduce the risks of liver dysfunction and leukopenia.Immunomodulator can be used as adjuvant treatment for patients with primary Graves' disease.3.Systematic Review: The results of this meta-analysis shows that selenium in adjuvant treatment of Graves' disease can significantly improve the thyroid function.The levels of FT3 and FT4 were significantly decrease and the level of TSH was increased.Besides,selenium combined with antithyroid drugs in adjuvant treatment of Graves' disease can significantly improve the levels of autoantibodies.The levels of TPOAb,TGAb,TRAb,IgA and IgG were significantly decreased.