| Objective: The application of infliximab(IFX)has improved the mucosal healing rate of inflammatory bowel disease(IBD),reduced complications,and significantly improved the prognosis and quality of life of children with IBD.However,some children have primary or secondary unresponsiveness to IFX treatment,which affects the drug efficacy.Therefore,IFX therapeutic drug monitoring(TDM)is very important.There is relatively little research on active TDM of IFX in children with IBD.The aim of this study is to explore the role of active TDM in optimizing drug use and guiding treatment strategy adjustment in children with IBD treated with IFX,and to bring more clinical benefits to IBD patients.Methods: The prospective clinical study was using a non randomized concurrent controlled study method.The pediatric inflammatory bowel disease were treated with IFX in the Pediatric Digestive Department of Shengjing Hospital Affiliated to China Medical University between September 2020 and December 2022 were selected into our study.Inclusion criteria:(1)IBD was diagnosed and treated with IFX regularly;(2)Age from 0 to 14 years old.Exclusion criteria:(1)Patients who use biological agents other than IFX;(2)Patients with serious organic diseases,hepatitis B,tuberculosis and tumor;(3)Patients without regular follow-up;(4)Patients treated for less than 14 weeks.Grouping: Divided into active TDM group and control group according to the wishes of patients and guardians.According to the rules of children’s IBD guidelines of IFX,the control group did not monitor IFX blood drug concentration during the treatment period,and adjust the treatment plan based on clinical,biochemical,endoscopic,and other results;The active TDM group began monitoring IFX blood concentration and Antibodies to IFX(ATI)concentration before the first maintenance remission treatment(14th week of medication),and adjusted treatment strategies based on TDM results.Statistical indicators: the clinical symptoms,laboratory indicators,IFX blood concentration,ATI concentration,IFX dose,program adjustment strategies,the Pediatric Crohn’s disease activity index(PCDAI),and Pediatric ulcerative colitis activity index(PUCAI)in the active TDM group and the control group were recorded respectively.calculating clinical remission rate and sustained remission rate in 14 th,30th,54 th,78th and 102 th week of treatment in two groups.Results:A total of 57 children,including 39 in the active TDM group and 18 in the control group.There was no difference in disease classification and sex ratio between the two groups.The results showed that 7 cases had primary unresponsiveness(12.3%,7/57),and 8 cases had secondary unresponsiveness(16.0%,8/50).At the 14 th week of IFX treatment,the remission rate in the active TDM group was 82.1%(32/39),which was higher than that in the control group(66.7%,12/18),but the difference was not statistically significant(P>0.05).At week 30,24 out of 27 cases in the active TDM group showed both continuous remission and remission.the remission and sustained remission rate of 88.9%.16 out of 18 cases in the control group showed both remission and sustained remission.The remission rate and sustained remission rate of88.9%,with no statistically significant difference(P>0.05).At the 54 th week of IFX treatment,although there was no statistically significant difference in the remission rate between the active TDM group and the control group(78.3% vs 61.1%;18/23 vs11/18,P>0.05),the sustained remission rate in the active TDM group(78.3%,18/23)was higher than that in the control group(44.4%,8/18),with a statistically significant difference(P<0.05).Starting from week 78,the remission rate and sustained remission rate of the active TDM group were higher than those of the control group,with statistically significant differences(92.9% vs 55.6%;78.6% vs 38.9%,P<0.05).The same trend was observed in week 102.After active TDM monitoring at each treatment node,a total of 18 patients with IFX blood drug concentration<3ug/ml were found.After adjustments such as increasing IFX dose,shortening IFX medication interval,and adding immunosuppressants,12 patients with IFX blood drug concentration>3ug/ml achieved clinical remission at the next statistical node.The remaining 6 patients still had IFX blood drug concentration<3ug/ml,and did not respond clinically.Some switched to other biological agents.Conclusions: 1.IFX has primary and secondary unresponsiveness during the treatment of pediatric inflammatory bowel disease.2.Adjusting the treatment strategy based on the results of IFX active TDM can significantly improve the clinical remission rate at 78 th and 102 th week of treatment,and can improve the sustained response rate after 54 th week of treatment.3.There is a correlation between IFX drug concentration levels and clinical remission of IBD.Based on the results of IFX active TDM,strategies such as increasing medication dose,shortening medication interval,and adding immunosuppressants are effective in maintaining sustained remission of pediatric inflammatory bowel disease. |
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