To Evaluate The Efficacy And Safety Of Thalidomide In The Treatment Of Moderate To Severe Active Inflammatory Bowel Disease In Children

Objective: To evaluate the efficacy and safety of thalidomide in the treatment of moderate to severe active IBD in children.Method: We collected data from children with moderate to severe active IBD given thalidomide in the Pediatric Gastroenterology Department of the First Hospital of Jilin University from January 1,2015 to December 31,2020.Thalidomide was given at a dose of 1-2mg/kg orally before going to bed,once a day.The clinical data were collected at 0,4,8,12,26 and 52 weeks after thalidomide treatment,including age of onset,age of thalidomide application,clinical symptoms,laboratory indexes,colonoscopy results,nutritional status,adverse reactions,secondary infection before and after thalidomide application,etc.Efficacy and safety of thalidomide in the treatment of children with moderate to severe active IBD were evaluated and the efficacy of thalidomide for CD and UC were compared.Statistical method: Data analyses were performed using SPSS version 26.0 software,Variables were presented as count with percentages for categorical variables and median with interquartile range(IQR)for continuous variables to describe the findings.PCDAI score,PUCAI score,laboratory indicators(ESR,CRP,PLT,Alb,Hb)were analyzed by repeated measures analysis of variance,and Weight Z-score,endoscopy score were tested by paired sample rank test.A two-sided P<0.05 indicated statisticalsignificance.Results: A total of 18 children were included in the study,including 10 cases of CD,7 cases of UC and 1 case of IBDU.Two of them(1 case of CD,1 case of IBDU)did not complete the 52 week follow-up and were not included in the result statistics.1)Disease activity: In the total of 16 children,9 CD cases achieved clinical remission at 26 weeks and sustained remission to 52 weeks.And in 7 cases of UC,2 cases(28.6%)showed clinical response,5 cases(71%)achieved clinical remission at 26 weeks,and all achieved clinical remission at 52 weeks.PCDAI score or PUCAI score were evaluated at 0,26,and 52 weeks,the average PCDAI and average PUCAI decreased compared with the previous one,and the difference was statistically significant(P<0.05).At 26 weeks and 52 weeks,no significant difference were found in clinical response rate and clinical remission rate between children with CD and UC(P>0.05).2)Endoscopic score: In the total of 16 children,4 out of 9 CD patients achieved mucosal remission and 2 cases achieved mucosal healing at 52 weeks.Endoscopic score were calculated as 10(7.5-14.5)and 3(0.5-4.5)at 0 week and 52 weeks respectively,with statistically significant(P<0.05).In UC patients,4 out of 7 cases achieved mucosal remission and 1 achieved mucosal healing at 52 weeks.Endoscopic score were calculated as 3.0(2.0-3.0)and 1.0(1.0-2.0)at 0 week and 52 weeks respectively,with statistically significant(P<0.05).At 52 weeks,there was no significant difference in mucosal remission rate and mucosal healing rate between children with CD and UC(P>0.05).3)Laboratory indicators: Compared with baseline,ESR,CRP,PLT of CD and UC children decreased in different degrees during follow-up,and Hb and Alb were increased at different degrees,and the difference was statistically significant.The mean difference of ESR in CD children at 52 weeks and 0 weeks was larger than that of UC children at 52 weeks and 0 weeks,and the difference was statisticallysignificant(P<0.05).The mean difference of CRP,PLT,Hb and Alb in CD and UC children was not statistically significant at 52 weeks and 0 weeks.4)Nutritional status: In CD patients,the weight Z-score were-2(-3 ~-0.5)and-0.5(-1.5 ~ 0.00)at baseline and 52 weeks respectively with statistically significant(P<0.05).In UC patients,the weight Z-score were-1.5(-2.5 ~-0.5)and 0.00(-0.5 ~ 0.5)at baseline and 52 weeks respectively with statistically significant(P<0.05).5)Adverse reactions: In the period of follow-up,a total of 8 cases(50%)had adverse reactions with 2 cases of lethargy(12.5%),2 cases of numbness in hands and feet(12.5%),1 case of dizziness(6.3%),1 case(6.3%)of peripheral neuritis,2 cases(12.5%)of neutropenia.Most adverse reactions could disappear and recovered with thalidomide dose-reduced or withdrawal.6)Secondary infection: At baseline,6 cases(37.5%)had secondary infection,while after treatment,only 1 case had secondary infection.In conclusion: 1.Thalidomide was clinically efficacious in the treatment of children with moderate to severe active CD and UC,inducing clinical remission and improving nutritional status.However,long-term maintenance of remission and the safety still need to be further investigated.2.The incidence of adverse reactions of thalidomide in the treatment of IBD in children is high,but most are mild.Most of them can be reversed after reduction or withdrawal of thalidomide.However,more frequent monitoring should be given to avoid irreversible adverse reactions.