Efficacy And Safety Analysis Of Vedolizumab In The Treatment Of Inflammatory Bowel Disease

Background:Therapy of inflammatory bowel disease(IBD)has entered the era of biological agents.Vedolizumab(VDZ)is a new humanized monoclonal antibody which can bind to α4β7 integrin on T lymphocytes,block its interaction with mucosal addressin cellular adhesion molecule-1(MAd CAM-1)on intestinal endothelial cells,thereby interfering with the migration of lymphocytes to the intestine to achieve the effect of inhibiting intestinal inflammation.In 2020,VDZ was approved for the therapy of adult patients with ulcerative colitis(UC)and Crohn’s disease(CD)in China.Objective:To evaluate the efficacy and safety of VDZ in inducing remission in patients with moderate to severe IBD,and to provide a reference for the future clinical use of VDZ in the therapy of IBD patients.Methods:A total of 38 IBD patients(UC:n=25,CD:n=13)treated with VDZ in the Department of Gastroenterology of the First Affiliated Hospital of Dalian Medical University from November 2020 to January 2023 were retrospectively enrolled,and patients’baseline data were recorded.The clinical symptoms(diarrhea,bloody stools)of UC patients were observed and the laboratory indexes were compared before and after VDZ therapy,including white blood cell(WBC),hemoglobin(HB),platelet(PLT),albumin(Alb),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR).The efficacy of UC was assessed according to the Partial Mayo score and Mayo endoscopic scores while the efficacy of CD was assessed according to the Crohn’s Disease Activity Index(CDAI)and Simple Endoscopic Score for Crohn’s Disease(SES-CD),respectively.The main observed parameters included clinical response rate,clinical remission rate,biological response rate,biological remission rate,endoscopic response rate and endoscopic remission rate at week 14 of VDZ therapy in IBD patients.Based on their previous exposure to biologics,38 IBD patients were divided into VDZ first-line group(20 patients)and VDZ second-line group(18 patients)to compare the clinical efficacy between the two groups.Adverse events were recorded during VDZ therapy period.Results:1.The results of VDZ therapy for UC(1)General data:A total of 25 UC patients were included.Among these patients,44%were male with the average age of 50.68±16.44 years old.The median course of disease was 4.0(1.34-9.50)years,and 10(40%)patients had previously received biologic therapy.(2)Symptom improvement:At week 14,the frequency of diarrhea and bloody stools decreased significantly as compared with that before the therapy(P<0.001).At week 14 of VDZ therapy,the average partial Mayo score was 2 points which was statistically lower than the baseline value of 8 points(P<0.001).(3)Clinical response and remission rate:At week 14,23 patients achieved clinical response,the clinical response rate was 92%(23/25),13 patients achieved clinical remission,the clinical remission rate was 52%(13/25).(4)Laboratory indexes:1)At week 14 of VDZ therapy,the WBC count was 5.94(5.31-7.37)×10~9/L which was statistically lower than the baseline value of 7.12(5.55-8.38)×10~9/L(P=0.045).2)At week 14 of VDZ therapy,the PLT count was 237(193.5-283)×10~9/L which was statistically lower than the baseline value of 254(216-311.5)×10~9/L(P=0.015).3)At week 14 of VDZ therapy,the CRP level was 3.13(3.13-4.9)mg/L which was statistically lower than the baseline value of 7.71(3.16-13.5)mg/L(P=0.046).4)At week 14 of VDZ therapy,the albumin level was(39.90±4.38)g/L which was statistically higher than the baseline value of(36.83±4.31)g/L(P=0.003).5)There was no statistical difference between ESR and BMI(P>0.05).(5)Biological response and remission rate:The CRP level of 16 UC patients was>5mg/L before the therapy,and at week 14 of VDZ therapy,13 patients achieved biological response,the biological response rate was 81.25%(13/16),and 12 patients achieved biological remission,the biological remission rate was 75%(12/16).(6)Endoscopic response and remission rate:At week 14 of VDZ therapy,5 UC patients undertook colonoscopy re-examination.All of them achieved endoscopic responses,and 3 patients achieved endoscopic remission.The endoscopic response and remission rate was 100%and 60%,respectively.2.The results of VDZ therapy for CD(1)General data:A total of 13 CD patients were included.Among these patients,69.2%were male with the median course of disease was(43.92±33.00)months.The average age was 27(25-43)years old,61.5%had a history of surgery,and 61.5%had prior exposure to biologics.(2)Symptom improvement:At week 14 of VDZ therapy,the CDAI score was133.7(42.8-172.3)points which was statistically lower than the baseline value of 258.7(235.3-335.7)points(P<0.001).(3)Clinical response and remission rate:At week 14 of VDZ therapy,11 patients achieved clinical response,the clinical response rate was 84.6%(11/13),and 9 patients achieved clinical remission,the clinical remission rate was 69.2%(9/13).(4)Laboratory indexes:1)At week 14 of VDZ therapy,the HB was 127.31±21.75 g/L which was statistically higher than the baseline value of 119.77±21.36 g/L(P=0.032).2)There was no statistical difference between albumin level,CRP,ESR,WBC,PLT and BMI before and after the therapy(P>0.05).(5)Biological response and remission rate:The CRP level of 6 patients with CD were abnormal at baseline(>5mg/L),only 1 patient achieved biological remission at week 14 of VDZ therapy,both the biological response rate and remission rate were 16.7%.(6)Endoscopic response and remission rate:At week 14 of VDZ therapy,5 CD patients undertook colonoscopy re-examination.3 patients achieved endoscopic response,1 patient achieved endoscopic remission.The endoscopic response and remission rate was 60%(3/5)and 20%(1/5),respectively.3.The efficacy comparison between VDZ first-line and second-line therapyThe enrolled 38 patients with IBD were divided into VDZ first-line group of 20 patients and second-line group of 18 patients.The effective rate in VDZ first-line group was 95%(19/20)and the effective rate in VDZ second-line group was 83.3%(15/18).Comparison of the effective rate between the 2 groups showed no statistical difference(P=0.328).4.The safety of VDZ therapyAt week 14 of VDZ therapy,the adverse events were mainly manifested as joint pain 4.7%(2/43),delayed allergic reaction 2.33%(1/43),herpes zoster 2.33%(1/43),and the overall adverse event rate of VDZ was 9.3%(4/43).Conclusions:VDZ therapy showed significant clinical efficacy in patients with moderate to severe UC and CD.Clinical and biological remission can be obtained through short-term induction therapy in favor of promoting mucosal healing.VDZ therapy has a high safety profile with low rate of adverse events in patients with moderate to severe UC and CD.