Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy

BACKGROUND Infliximab trough level(ITL)severely affects therapeutic outcomes of Crohn’s disease(CD)patients under infliximab(IFX).Recently,frontier research has focused on identifying ITL based on different therapeutic targets.Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy,studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas.AIM To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODS CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected.ITL and inflammatory biomarkers were continuously monitored during the therapy.The Step I study was conducted from weeks 14 to 54 of IFX treatment.The Step II study was conducted from weeks 54 to 108 of IFX treatment.Endoscopic outcomes were defined as endoscopic activity(Crohn’s disease endoscopic index of severity score>2 points or Rutgeerts score>i1)and endoscopic remission(Crohn’s disease endoscopic index of severity score≤2 points or Rutgeerts≤i1).Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTS At week 14,low ITL[odds ratio(OR)=0.666,95%confidence interval(CI):0.514-0.862,P<0.01]and high fecal calprotectin(FCP)level(OR=1.002,95%CI:1.001-1.004,P<0.01)increased the risk of endoscopic activity at week 54.At week 54,low ITL(OR=0.466,95%CI:0.247-0.877,P<0.01)and high C-reactive protein(CRP)level(OR=1.590,95%CI:1.007-2.510,P<0.01)increased the risk of endoscopic activity at week 108.At week 14,ITL≤5.60μg/mL[area under the curve(AUC)=0.83,95%CI:0.73-0.90,P<0.001]and FCP>238μg/g(AUC=0.82,95%CI:0.72-0.89,P<0.001)moderately predicted endoscopic activity at week 54.ITL≤5.60μg/mL in combination with FCP>238μg/g indicated 82.0%possibility of endoscopic activity.At week 54,ITL≤2.10μg/mL(AUC=0.85,95%CI:0.72-0.93,P<0.001)and CRP>3.00 mg/L(AUC=0.73,95%CI:0.60-0.84,P=0.012)moderately predicted moderate endoscopic activity at week 108.ITL≤2.10μg/mL in combination with CRP>3.00 mg/L indicated 100.0%possibility of endoscopic activity.From weeks 14 to 54 of IFX treatment,patients with ITL>5.60μg/mL had higher rate of endoscopic relapse free survival than those with ITL≤5.60μg/mL(95.83%vs 46.67%).From weeks 54 to 108 of IFX treatment,patients with ITL>2.10μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL≤2.10μg/mL(92.68%vs 30.77%).CONCLUSION Combination of ITL,CRP,and FCP contribute to long-term endoscopic prognosis monitoring.During IFX maintenance treatment,low ITL,high CRP level,and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Ulcerative colitis worsened after Clostridium difficile infection:Efficacy of infliximab

The incidence of Clostridium difficile (C. difficile) infection (CDI) is 1.8%-5.7% in admitted patients with ulcerative colitis (UC). CDI can worsen UC and increase the risk for colectomy or even death, thus necessitating therapy escalation, such as increasing the corticoid therapy or starting a biologic treatment. Several reported cases with infliximab therapy have provided favorable outcomes in UC patients with CDI, suggesting that infliximab treatment may be protective; however, the optimal infliximab treatment regimen for UC patients with CDI remains to be established. Here, we report a case of worsening UC in the presence of recurrent CDI. The patient had received prior ciprofloxacin and immunosuppressive therapy during a prolonged hospital stay. The deterioration in the patient&#x02019;s condition likely resulted from the ability of C. difficile to promote relapsing of UC by activating the immune response. Ultimately, the patient was treated with a high dose of infliximab after a low trough level of infliximab at week 8 was identified, yielding better clinical results. Infliximab was found to be safe after repetitive episodes of CDI. The trough level of infliximab was therefore a useful indicator to guide therapy and correlated well with the patient&#x02019;s outcome.

Association of polymorphisms in C1orf106,IL1RN,and IL10 with post-induction infliximab trough level in Crohn’s disease patients

Background:Trough levels of the post-induction serum infliximab(IFX)are associated with short-term and long-term responses of Crohn’s disease patients to IFX,but the inter-individual differences are large.We aimed to elucidate whether single gene polymorphisms(SNPs)within FCGR3A,ATG16L1,C1orf106,OSM,OSMR,NF-jB1,IL1RN,and IL10 partially account for these differences and employed a multivariate regression model to predict patients’post-induction IFX levels.Methods:The retrospective study included 189 Crohn’s disease patients undergoing IFX therapy.Post-induction IFX levels were measured and 41 tag SNPs within eight genes were genotyped.Associations between SNPs and IFX levels were analysed.Then,a multivariate logistic-regression model was developed to predict whether the patients’IFX levels achieved the threshold of therapy(3 lg/mL).Results:Six SNPs(rs7587051,rs143063741,rs442905,rs59457695,rs3213448,and rs3021094)were significantly associated with the post-induction IFX trough level(P=0.015,P<0.001,P=0.046,P=0.022,P=0.011,P=0.013,respectively).A multivariate prediction model of the IFX level was established by baseline albumin(P=0.002),rs442905(P=0.025),rs59457695(P=0.049),rs3213448(P=0.056),and rs3021094(P=0.047).The area under the receiver operating characteristic curve(AUROC)of this prediction model in a representative training dataset was 0.758.This result was verified in a representative testing dataset,with an AUROC of 0.733.Conclusions:Polymorphisms in C1orf106,IL1RN,and IL10 play an important role in the variability of IFX post-induction levels,as indicated in this multivariate prediction model of IFX levels with fair performance.