Efficacy Of Verdelezumab Combin With Glucocorticoid In The Treatment Of Moderate And Severe Ulcerative Colitis

Background:Ulcerative colitis(UC)is a chronic,nonspecific inflammatory disease that mainly affects the colon and rectum.At present,the etiology of ulcerative colitis is not fully understood.Some scholars believe that ulcerative colitis is an autoimmune disease,but it is generally believed that the pathogenesis of ulcerative colitis is the result of the comprehensive interaction of genes,immune influence and host reaction caused by foreign substances.Ulcerative colitis is mainly located in the mucosa and submucosa of the sigmoid colon and rectum,and can also extend to the descending colon,or even the whole colon,showing extensive lesions of the large intestine.This disease occurs at any age,but is common in young people.It has a long course and can recur even with effective treatment.There are many clinical symptoms of ulcerative colitis,and the initial manifestations can be in many forms.Among them,diarrhea,bloody diarrhea,mucoempyema and blood are the most common early symptoms.Other symptoms such as posterior hypersomia,vomiting,abdominal pain,and weight loss are also common.Mild patients have mild symptoms and may present only with diarrhea symptoms,and the frequency of diarrhea is less than 5 times a day.The main manifestations of severe diarrhea are watery diarrhea or bloody stools,more than 10 or even dozens of times a day,fever symptoms,abdominal pain is serious,pulse rate is more than 90 times/min,body temperature can exceed38.5℃,severe symptoms of systemic poisoning.Moderate patients have clinical symptoms between mild and severe.Previous treatments for ulcerative colitis include immunosuppressants(azathioprine,methotrexate,etc.),glucocorticoids,5-aminosalicylate(5-ASA)and other drugs.Immunosuppressants are effective and can maintain treatment,but most patients cannot tolerate the potential side effects of their long-term use.Late glucocorticoids can produce adverse outcomes of hormone dependence or hormone inefficacy,so although they can produce effective induction therapy for ulcerative colitis,long-term maintenance of therapy is difficult.Biologics have been widely used in clinic in recent years and have changed the course of patients’disease.Verdelizumab is different from Infliximab in systemic immunosuppression.It targets a4b7integrin and belongs to a novel biologics that selectively inhibits lymphocyte migration in the intestinal tract.At present,a number of studies have confirmed that videclizumab has obvious effect on inducing and maintaining remission of ulcerative colitis,and has more advantages in the safety of long-term maintenance treatment,which is a better choice for clinical treatment of ulcerative colitis.However,the clinical efficacy of Vidrecizumab alone and combined with immunosuppressants such as methotrexate has been reported,but whether combining with other drugs such as glucocorticoids can achieve better efficacy and lower incidence of adverse reactions has not been reported.The purpose of this study was to investigate whether the combination of Vedrizumab with other drugs,such as glucocorticoids,can achieve better efficacy.Objective:To explore and analyze the clinical efficacy of videclizumab combined with glucocorticoid in the treatment of moderate-to-severe ulcerative colitis,and evaluate its safety,so as to provide reference for the selection of clinical treatment for moderate-to-severe ulcerative colitis.Method:59 patients with moderate to severe ulcerative colitis admitted to The First Affiliated Hospital Of Henan University from January 2021 to October 2022 were selected as the research objects.Among them,36 patients received simplex verticulizumab treatment(VDZ group).The standard treatment regimen was once at week 0,2 and 6,and once every 8 weeks.The treatment cycle was 22 weeks,and the dosage was300mg.Patients with secondary unresponse were given intensive drug therapy with 300mg infusion of Vederizumab every 4 weeks to improve clinical response.The remaining 23 patients received verderizumab combined with glucocorticoid therapy(combination group).The administration plan of verderizumab was the same as above,and hydrocortisone was selected as intravenous drops,100mg,once a day,for a course of 1 week.The treatment plan and regular review plan have been fully communicated with the patients,obtained their consent and signed informed consent.The clinical observation points were 0,6,14,30 and 54 weeks.The outcome measures included serological indicators,histological indicators,clinical response rate,endoscopic improvement rate,clinical remission rate,mucosal healing rate,recurrence rate and adverse reactions.The serological indicators included white blood cell(WBC)count,hemoglobin(Hb),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and albumin(ALB).A clinical response was defined as a decrease≥1 point in blood stool score or 0 or 1 point in this item,a decrease≥30%or≥3 points in modified Mayo score from baseline.Clinical remission was defined as an improved Mayo score≤2 and no single score>1.Endoscopic improvement was defined as a decrease≥1 point in Mayo endoscopic score.Mucosal healing was defined as Mayo endoscopic score=0.Adverse reactions mainly included oral ulcers,allergic reactions,herpes zoster virus infection and tuberculosis infection.Results:(1)Complete clinical data were collected from all 59 subjects.Statistical comparison of general data and process characteristics showed that there were no significant differences in gender,age,course of disease,BMI,clinical type,severity,disease stage and lesion range between the two groups(P>0.05).(2)The changes of abdominal pain,diarrhea,hematochezia,and posterior rigor were statistically analyzed at week 0,6,14 and 30.Intra-group comparison showed that the incidence of abdominal pain,diarrhea,hematochezia,and posterior liesia were significantly improved in the 2 groups at week 0,6,14and 30,and the differences were statistically significant compared with week 0(P<0.05).Comparison between groups showed that at week 0 and 30,there was no significant difference in clinical symptoms between the two groups at each time point(P>0.05).At the 6th week,the improvement degree of diarrhea and hematochezia in combination group was better than that in VDZ group,the difference was statistically significant(P<0.05).At the 14th week,the improvement of symptoms of abdominal pain,diarrhea,hematochezia and posterior liesia in combination group was better than that in VDZ group,with statistical significance(P<0.05).(3)The changes of WBC count,Hb,CRP,ESR and ALB of subjects in the 2 groups were statistically analyzed at week 0,6,14 and 30,respectively.Comparison between groups showed that there was no significant difference in serological indexes between the two groups at each time point(P>0.05).Intra-group comparison showed that WBC count,Hb,CRP,ESR and ALB indexes were significantly improved in 2 groups at week 0,6,14 and 30,and the differences were statistically significant compared with week 0(P<0.05).(4)The changes of Mayo scores in the 2 groups were statistically analyzed at week 0,6,14 and 30,respectively.Intra-group comparison showed that Mayo scores of subjects in the 2 groups were significantly improved at week 0,6,14 and 30,with statistical significance compared with week 0(P<0.05).Inter-group comparison showed that at week 0 and 30,there was no significant difference in Mayo scores between the two groups(P>0.05).At the 6th and 14th week,Mayo scores in the combination group were better than those in the VDZ group,with statistical significance(P<0.05).(5)The clinical response rate,clinical remission rate and mucosal healing rate of subjects in the 2groups were statistically analyzed at the 6th,14th and 30th week,respectively.Intra-group comparison showed that Mayo scores were significantly improved in both groups at week 14 and 30,and the differences were statistically significant compared with week 6(P<0.05).Comparison between groups showed that at the 6th and 30th week,there was no significant difference in clinical response rate and clinical remission rate between the 2 groups(P>0.05).At the 14th week,the clinical response rate and clinical remission rate of the combination group were better than those of the VDZ group,with statistical significance(P<0.05).There was no significant difference in mucosal healing rate between the two groups at each observation time point(P>0.05).The intestinal inflammation was significantly relieved under endoscopy.(6)During the treatment period,there were 2 cases of primary unresponsiveness in the VDZ group(5.6%(2/36);Secondary unresponsiveness occurred in 4 cases(11.1%,4/36).In the combination group,there was no primary loss of response,and 1 case(4.3%)suffered secondary loss of response,which was recovered after intensive treatment.In terms of the difference in the occurrence of disresponse,there was no significant difference between the VDZ combination and the combined group(x~2=1.0290,P=0.3104).(7)Some subjects in both groups had drug-related adverse reactions during treatment,mainly manifested as oral ulcer,allergic reaction,herpes zoster virus and tuberculosis infection.There was no statistical significance in the incidence of adverse reactions between the two groups(P>0.05).(8)16 patients(44.4%)had relapsed in the VDZ group and 3 patients(13.0%)in the combination group at the 54th week of follow-up,the difference between groups was statistically significant(x~2=4.9814,P=0.0256)..Conclusions:(1)VDZ combined with glucocorticoid can improve the clinical symptoms of moderate to severe ulcerative colitis and improve the early clinical response rate and remission rate.(2)VDZ combined with glucocorticoids can reduce the recurrence of moderate to severe ulcerative colitis,improve the long-term prognosis of patients and achieve long-term remission.