| Background and objective: As the first biologic agent to treat Crohn’s disease,Tumor necrosis factor alpha antagonist(anti-TNF-α)has dramatically altered the course of the disease and improved prognosis for CD patients.Infliximab and adalimumab are the two most common types of TNF antagonist and remain the top biologics options for patients with CD.No head-to-head comparation of the efficacy and tolerability of IFX and ADA in the Chinese population was reported.The purpose of this study was to evaluate the efficacy and safety profile of IFX and ADA in Chinese adult CD patients in real-world settings.Methods: A retrospective analysis was conducted to compare clinical efficacy and safety profile of IFX and ADA using data of adult patients with CD who were treated with IFX or ADA in the Gastroenterology Department of the Second Xiangya Hospital of Central South University from January 2017 to April 2022.Clinical efficacy evaluation included clinical symptoms(CDAI),serological indicators(CRP),endoscopic data(SES-CD),radiological data(CTE)and further analysis of reasons for treatment failure,drug concentration monitoring,drug withdrawal or replacement,surgery and hospitalization,dose intensification,cumulative remission rate and cumulative remission rate accounting for patients regained remission after dose intensification.Safety assessment included adverse events at up to 12 months and by the end of follow-up.The primary efficacy endpoint is clinical remission(CDAI<150)at 12 weeks and 12 months.Secondary efficacy endpoints include: serological remission(CRP≤5mg/L)and endoscopic remission(SES-CD<3)at 12 weeks and 12 months,radiological response and radiological remission at 12 months.The primary safety endpoint is the rate of patients with adverse events during one year of treatment.The secondary safety endpoint is the rate of adverse events per 100 patient-years during the follow-up.Multivariate logistic regression analysis was used to find the associated factors of 12-week clinical remission,12-month clinical remission and 12-month endoscopic remission.Results:A total of 221 CD patients were included,of those 126 in the IFX treatment group and 95 in the ADA treatment group.(1)In the induction period(12 weeks),there was no significant difference in the clinical remission rate,serological remission rate and endoscopic response rate between the IFX treatment group and the ADA treatment group(clinical remission: IFX 96/125;76.8% vs.ADA 76/94;80.9%,P=0.470;serological response: IFX 71/116;61.2% vs.ADA 62/89;69.7%,P=0.716;endoscopic response: IFX 18/63;34.7% vs.ADA 25/72;34.7%,P=0.473).(2)Similarly,in terms of efficacy evaluation during the remission period(12 months),there was no significant difference in clinical remission rate,serological remission rate and endoscopic response rate between IFX treatment group and ADA treatment group(clinical remission:IFX 71/90;78.9% vs.ADA 62/74;83.8%,P=0.426;serological response:IFX 57/88;64.8% vs.ADA 52/74;70.3%,P=0.782;endoscopic response:IFX 20/52;38.4% vs.ADA 22/56;39.2%,P=0.423).However,in patients who did not receive or add glucocorticoids,azathioprine(AZA)or methotrexate(MTX)during the induction period,the ADA-treated group(33/70;46.5%)had higher serological remissions rates than that in the IFX treatment group(46/63;73.1%),the difference was statistically significant(P=0.020).Furthermore,there was a trend favoring ADA treatment in terms of endoscopic response during the induction period(IFX6/40;15.0% vs.15.0% vs.ADA 17/55;30.9%,P=0.074).In patients with colonic lesions during remission treatment,the endoscopic remission rate in the ADA treatment group(6/9;66.7%)was higher than that in the IFX treatment group(4/19;40.0%),the difference was statistically significant(P=0.010).(3)In general,no difference was found in number of treatment failures due to different reasons between the IFX treatment group and the ADA treatment group,whereas more patients in the ADA treatment group had dose-intensification after secondary loss of response than the IFX treatment group,and the difference was statistically significant(P=0.035);the number of patients who added AZA,MTX or thalidomide after secondary loss of response in the IFX treatment group was more than that in the IFX treatment group(P=0.098).In the monitoring of blood drug concentration recorded during the medication,the probability of low blood drug concentration and/or high anti-antibody concentration in the IFX treatment group was significantly higher than that in the ADA treatment group(IFX 44/73;60.3% vs.ADA15/62;24.2%,P<0.001).The number of patients who stopped/changed drugs due to disease recurrence in the ADA treatment group(10/21;47.6%)was higher than that in the IFX treatment group(8/36;22.2%),and the difference was statistically significant(P=0.047).The cumulative clinical remission rate in the IFX treatment group after dose optimization was higher than that in the ADA treatment group(P=0.087).(4)Multivariate logistic regression analysis showed that the disease duration before biologics less than the mean(46.28 months)was a predictor of clinical remission in the induction period,and baseline CRP>5mg/L was a predictor of poor clinical remission in the induction period;age of onset A2 and 12-Week CRP decreased by more than 50%from baseline was a predictor of clinical remission during remission;disease behavior phenotype of B2+B3 and 12-week CRP>5mg/L were predictors of poor clinical remission;12-week CRP decreased by more than50% from baseline and baseline SES-CD<3 was the predictor of endoscopic remission,and the lesion site being small intestine and the disease behavior phenotype of B2+B3 were the predictors of poor endoscopic remission.(5)Over the course of one-year anti-TNF-α drug treatment,the proportion of overall adverse reactions occurred in the two groups was similar(IFX 43/126;34.1% vs.ADA29/95;30.5%,P=0.572),of which the rate of acute injection site reactions in the IFX treatment group was higher than that in the ADA treatment group(IFX 8/126;6.3% vs.ADA 0/95;0%,P=0.010).Extending the observation time to the end of follow-up,found that the number of acute injection site adverse events(per 100 person-years)in the IFX treatment group was still higher than that in the ADA treatment group(IFX 26.2 vs.ADA 3.2).Conclusion:Our research results show that:(1)In terms of efficacy evaluation: No difference was found on clinical efficacy between IFX and ADA both in the induction and remission stages.In the induction phase treatment,IFX needs to combine or add with immunosuppressants,and/or glucocorticoids to achieve the same serological remission as ADA;in the remission phase treatment,ADA shows better efficiency for colonic CD than IFX.(2)In terms of efficacy predictors:(1)Early use of TNF-αpreparations can promote clinical remission during the induction period;(2)Young patients are more likely to maintain clinical remission;(3)CRP can reflect disease activity,and CRP at baseline and after the end of the induction period higher than 5mg/L indicates poor clinical remission;(4)small bowel type CD is more difficult to obtain endoscopic remission;(5)disease behavior phenotype of B2+B3 is a risk factor for poor clinical and endoscopic remission,while a decrease over 50% from baseline of CRP at12 weeks facilitates clinical and endoscopic remission.(3)In the monitoring of blood drug concentration,the incidence of low blood drug concentration and/or high anti-antibody concentration of IFX was significantly higher than that of ADA,and the number of doseenhanced patients in the ADA group was higher than that in the IFX group due to the low blood drug concentration.(4)In terms of the outcome of dose intensification,the cumulative clinical remission rate of the dose-intensive patients in the IFX group tends to be higher than that in the ADA group.(5)In terms of safety events,the probability of acute injection site reactions in the IFX-treated patients is higher than that in the ADA-treated group,but generally won’t affect the continuation of medication,and the overall adverse reactions in the two groups are basically the same.Our study reflects the use of TNF-α antagonists by Chinese CD patients in real clinical practice,which is beneficial for clinicians to target drugs and predict the efficacy of CD patients with different demographic characteristics and pathological characteristics.Larger and longer followup clinical studies will discuss the efficacy of early use of anti-TNF-αagents and the efficacy of TNF-α antagonists on patients with disease behavior of B2+B3,and to reflect the long-term efficacy and safety profile of IFX and ADA in the Chinese population. |
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