| Research background and purposeVedelizumab targets the a4b7 integrin,which is different from the systemic immunosuppression of infliximab and is a novel intestinal-selective biological agent.Multiple studies have demonstrated that vedolizumab is similar in efficacy to anti-tumor necrosis factor（TNF）drugs,but its safety is relatively high;and in patients who have failed previous hormone,immunosuppressive or biologic therapy It also has a certain clinical effect in patients,which can change the disease process and improve the quality of life of patients.This article investigates the efficacy and safety of vedolizumab in the treatment of moderate to severe ulcerative colitis（UC）and Crohn ’s Disease（CD）.Research objects and research methodsCollected from November 2020 to February 2022 in the Department of Gastroenterology,Jilin University First Hospital,diagnosed with ulcerative colitis or Crohn’s disease,aged 18-75,with moderate to severe disease status and using Vidley A total of 38 patients（24 in UC and 14 in CD）were treated with Zizumab,and the clinical data of the patients were retrospectively studied.Due to the different disease states and drug responses of patients,the drug administration methods in this study were divided into two types: standard drug therapy and intensive therapy.The standard treatment regimen is week 0,week 2,week 6,and week 14,followed by administration at 8-week intervals,with a dose of 300 mg.For patients with secondary loss of response,drug-intensive therapy can be tried to shorten the dosing time and change to intravenous infusion of vedolizumab 300 mg every 4 weeks to improve clinical response.（There is currently no uniform definition of primary and secondary loss response: however,it is generally accepted that primary loss responders are those who lack improvement in clinical signs and symptoms during induction therapy,and secondary loss responders are defined as those who respond to induction therapy but are subsequently maintained on maintenance.Loss of response during treatment [1]）.There are two clinical observation points in this study,which are the 14 th week after drug treatment（after 3 drug treatments）and the end point of this study（February2022）.The main results of observation are: 1.UC patients were observed for bloody stool and diarrhea at the 14 th week and at the end of the study,and the changes in Mayo score and Mayo endoscopic score were evaluated,and the clinical response rate,clinical remission rate and clinical response rate of the drug were further obtained.The mucosal healing rate should be compared with the changes of laboratory indicators before and after treatment,including: high-sensitivity C-reactive protein,erythrocyte sedimentation rate,hemoglobin and albumin.And observe the various adverse reactions of the patients during the medication.2.CD patients were observed at the 14 th week and the end point of the study.The CDAI index and simplified endoscopic score of Crohn’s disease（SES-CD）before and after treatment were compared,and the clinical response rate,clinical remission rate and mucosal healing rate of the patients after treatment were further evaluated.Due to the severe intestinal damage in CD patients under endoscopy,the full thickness of the intestinal wall can be involved,so the time of colonoscopy in CD patients can be appropriately extended to 14+8 weeks.In addition,the changes of perianal lesions were observed.At the same time,it is necessary to compare the changes of laboratory indicators before and after treatment,including: high-sensitivity C-reactive protein,erythrocyte sedimentation rate,hemoglobin,and albumin.To observe various adverse reactions in CD patients during the course of medication.In this study,the patients with primary or secondary loss of response to vedelizumab treatment were analyzed,and the treatment regimen of the patients with secondary loss of response was adjusted.Drug response can be regained.Statistical method: The measurement data that conform to the normal distribution are represented by `X±S,and the paired t test is used for statistical inference.Wilcoxon nonparametric rank sum test was used for statistical inference to compare whether the difference before and after treatment was statistically significant.There are two clinical observation points in this study,which are the 14 th week after drug treatment（after 3 times of drug treatment）and the end point of this study（February 2022）.The main results of observation are: 1.UC patients were observed for bloody stool and diarrhea at the 14 th week and at the end of the study,and the changes in Mayo score and Mayo endoscopic score were evaluated,and the clinical response rate,clinical remission rate and clinical response rate of the drug were further obtained.The mucosal healing rate should be compared with the changes of laboratory indicators before and after treatment,including: high-sensitivity C-reactive protein,erythrocyte sedimentation rate,hemoglobin and albumin.And observe the various adverse reactions of the patients during the medication.2.The 14 th week of CD patients and the observation of the end point of the study,the CDAI index and the simplified endoscopic score of Crohn’s disease（SES-CD）before and after treatment were compared,and the clinical response rate,clinical remission rate and mucosal healing rate of the patients after treatment were further evaluated.Due to the severe intestinal damage in CD patients under endoscopy,the full thickness of the intestinal wall can be involved,so the time of colonoscopy in CD patients can be appropriately extended to 14+8 weeks.In addition,the changes of perianal lesions were observed.At the same time,it is necessary to compare the changes of laboratory indicators before and after treatment,including: high-sensitivity C-reactive protein,erythrocyte sedimentation rate,hemoglobin,and albumin.To observe various adverse reactions in CD patients during the course of medication.In this study,the patients with primary or secondary loss of response to vedelizumab treatment were analyzed,and the treatment regimen of the patients with secondary loss of response was adjusted.Drug response can be regained.Statistical method: The measurement data that conform to the normal distribution are represented by X±S,and the paired t test is used for statistical inference.Wilcoxon nonparametric rank sum test was used for statistical inference to compare whether the difference before and after treatment was statistically significant.Research result1.UC: 23 patients entered the 14 th week observational study,and the results were: in the 14 th week of medication,the number of patients with diarrhea and bloody stools decreased compared with before（P = 0.01,P = 0.01）.In addition,the Mayo score and Mayo endoscopic score were both lower than those before treatment（P < 0.001,P = 0.002）.A total of 11 patients achieved clinical response at the 14 th week of treatment,the clinical response rate was 73.9%（17/23）,6 patients achieved clinical remission,the clinical response rate was 26.1%（6/23）,and 9 patients achieved endoscopic With a score of 0 or 1,the mucosal healing rate was 39.1%（9/21）.Compared with before treatment,CRP and ESR decreased（P = 0.012,P =0.039）,and hemoglobin and albumin increased compared with before treatment（P =0.022,P = 0.001）),and the difference was statistically significant.Among the 3 patients,10 patients entered the end-point study,and the average medication time was 34.40±8.53 weeks.The results were: the frequency of diarrhea and bloody stools in 10 patients was significantly lower than that before medication（P = 0.007,P = 0.007）,Mayo score and Mayo endoscopic scores were decreased compared with those before treatment（P = 0.008,P = 0.006）,the clinical remission rate was 60%（6/10）,and the mucosal healing rate was 50%（5/10）.Similarly,CRP and ESR decreased（P =0.007,P =0.005）,while hemoglobin and albumin increased（P =0.005,P =0.005）,and the difference was statistically significant.2.CD: 12 patients entered the 14 周 study observation,and the results were:CDAI score,SES-CD,high-sensitivity C-reactive protein,and erythrocyte sedimentation rate were all lower than those before treatment（P <0.001,P =0.012,P=0.01,P =0.027）,the albumin was higher than before treatment,（P =0.042）,the difference was statistically significant.The mean value of hemoglobin increased before and after treatment,but P = 0.26,and the difference was considered to be not statistically significant.The clinical response rate was 75%（9/12）,the clinical response rate was 66.7%（8/12）,and no patient achieved endoscopic mucosal healing during induction therapy.Observation of the end point of the study: 10 patients entered the end point of the study,and the average duration of medication was40.40±8.48 weeks.The CDAI score,SES-CD,high-sensitivity C-reactive protein,and erythrocyte sedimentation rate of the patients were all lower than those before treatment（P<0.001,P =0.017,P =0.028,P =0.048）,and albumin was higher than those before treatment（P =0.035）.),the difference was statistically significant.The mean value of hemoglobin increased before and after treatment,but P = 0.28,the difference was not statistically significant.Of the 10 patients who entered the study endpoint,7 achieved clinical remission during induction and further stabilized during maintenance therapy.Afterwards,2 patients achieved clinical remission during maintenance treatment,and the clinical remission rate of CD at the end of the study was 90%（9/10）,of which 1 patient achieved SES-CD score of 0 to achieve mucosal healing,and the patient was prescribed medication.At the 38 th week,the endoscopic scores of the remaining 9 patients were all ≥2.However,the UC and CD mucosal healing rates were statistically analyzed by Fisher’s exact probability method,and the result showed that there was no significant difference between the two（P = 0.141）.3.There are 7 patients with CD combined with perianal lesions,and 6 patients entered the end point of the study.Among them,4 patients were found to have anal fistula by perianal ultrasonography before treatment,but they were in the stable stage and did not need special treatment such as surgery and anti-inflammatory.,After vedelizumab treatment,the condition was relatively stable,there was no obvious perianal discomfort,and no antibiotics and other drugs were used for control.Among the other two patients: 1 patient had complex anal fistula and active perianal abscess before treatment,with unbearable pain and fever.After surgical fistula incision and suture drainage,Vidrilizumab was applied.Anti-combination hormone therapy,abdominal pain,diarrhea symptoms improved,but the fistula still did not heal for a long time,the perianal pain was obvious,and the drainage volume did not decrease,and another operation was performed.After using vedelizumab for 5 times After the treatment,he gave up continuing to use ustekinumab and changed to ustekinumab treatment.At present,the perianal lesions have been significantly improved.Another CD patient with ileocolostomy state had anal fistula and anal canal stenosis before vedolizumab treatment,and a small amount of pus flowed out of the anus intermittently,but there was no obvious perianal pain,and was treated with vedolizumab There was no significant change in the posterior perianal symptoms,and no surgical treatment or antibiotic anti-inflammatory treatment was given.4.The UC patients had a loss-of-response rate of 13%（3/23）and a secondary loss-response rate of 30.4%（7/23）to the vedezizumab antigen.Among them,4patients with secondary loss-response were treated by shortening the dosing interval.During the period,3 patients regained response,and the other 1 patient recovered after intensive treatment,but gradually reappeared secondary loss of response,and then changed to traditional Chinese medicine to continue treatment.The primary loss-response rate in CD patients was 8.3%（1/12）;the secondary loss-response rate was 8.3%（1/12）.Using the exact probability method to analyze the non-response rate of UC and CD,the difference was not statistically significant（P =0.216）.5.Among the 34 patients in this study,no serious infections such as Mycobacterium tuberculosis and cytomegalovirus were found;no infusion reactions,such as nausea,vomiting and other gastrointestinal reactions,no delayed allergic reactions,and unknown Causes of neuropsychiatric symptoms.Conclusion1.Vedelizumab has been widely used in IBD patients,regardless of whether it is UC or CD,first-line treatment or second-line treatment,it can achieve better clinical efficacy.2.For vedolizumab treatment to achieve mucosal healing,the mucosal healing rate of UC at the end of the study was 50 %,and the CD mucosal healing rate was10%,but there was no significant difference between the two（P = 0.141）.3.In the process of using vedolizumab,the problem of non-response cannot be avoided.This study found that the secondary loss of response rate of UC was 30.4%,and the secondary loss of response rate of CD was 8.3%.The difference was not statistically significant（P=0.216）.4.There is a correlation between the blood drug concentration of vedelizumab and the clinical efficacy.The higher the blood drug concentration,the higher the clinical remission and mucosal healing rate can be achieved.Therefore,patients have primary or secondary failure during clinical application.If the drug concentration is low,try to shorten the dosing interval,and increasing the blood drug concentration can improve the drug efficacy.However,there is no relevant research in China,and no statistical analysis has been carried out in this study.5.For patients with CD combined with perianal lesions,vedelizumab has no obvious effect.6.Vedelizumab has good safety,and no adverse events such as obvious infusion reactions,delayed allergic reactions,and serious infections have occurred.In addition,none of the patients in this study discontinued medication due to adverse drug reactions. |
PDF Full Text Request