BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thio...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.展开更多
BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated ...BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.展开更多
AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis(UC).METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on Jul...AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis(UC).METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on July 31, 2013. Inclusion criteria were:(1) Randomized controlled trial(RCT);(2) Patients treated for UC; and(3) Intervention was vedolizumab. The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, patient demographic information, response rate, remission rate, and adverse events. The primary outcome was clinical response rate, and the secondary outcomes were clinical remission rate and serious adverse events. Odds ratio(OR) with 95%CI were calculated for each outcome. RESULTS: Of 224 studies initially identified, three RCTs examining the use of vedolizumab meeting the inclusion criteria were included in the meta-analysis. All studies examined the use of vedolizumab at dosages ranging from 0.5 to 10 mg/kg body weight(one study used a standard dose of 300 mg). The follow-up periods were approximately 6 wk. The total number of patients in the intervention groups was 901, and in the control groups was 221. The mean age of the patients was approximately 41 years, and approximately half were males. The follow-up periods ranged from 43 d to 6 wk. The clinical response and remission rates were significantly higher for patients who received vedolizumab as compared to control patients(clinical response: OR = 2.69; 95%CI: 1.94-3.74, P < 0.001 and remission rate: OR = 2.72; 95%CI: 1.76-4.19, P < 0.001). Serious adverse events were not higher in patients that received vedolizumab.CONCLUSION: This analysis supports the use of vedolizumab for the treatment of UC.展开更多
The biologic antitumor necrosis factor alpha(anti-TNFα) agents have revolutionised the treatment of inflammatorybowel disease(IBD). However,some patients experience primary nonresponse,loss of response,or intolerance...The biologic antitumor necrosis factor alpha(anti-TNFα) agents have revolutionised the treatment of inflammatorybowel disease(IBD). However,some patients experience primary nonresponse,loss of response,or intolerance. Therefore,introducing a newer class of therapy with a mechanism of action that acts on different inflammatory pathways involved in IBD pathogenesis is appealing. Vedolizumab is a fully humanised monoclonal antibody that selectively targets α4β7 integrin. Based on the results of the pivotal clinical GEMINI trials,vedolizumab was approved for the treatment of adult patients with moderately to severely active ulcerative colitis(UC) and Crohn's disease(CD) refractory or intolerant to either conventional therapy or TNFα inhibitors. This review describes the efficacy,safety,and tolerability of vedolizumab reported in both randomized,controlled,clinical trials and from real-world experience in patients with UC and CD in order to identify its place in treatment algorithms for IBD.展开更多
BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)patients.AIM To assess the efficacy an...BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)patients.AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.METHODS A retrospective review of Australian and Oxford,United Kingdom data for UC patients.Clinical response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were assessed.Cox regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing them.Safety outcomes were recorded.RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were included.The clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo respectively.Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 mo.CONCLUSION VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.展开更多
BACKGROUND Fistula and intraabdominal abscess are common complications of Crohn’s disease(CD),but complex rectal fistula with abscess formation is rare.Tumor necrosis factor antagonists combined with percutaneous dra...BACKGROUND Fistula and intraabdominal abscess are common complications of Crohn’s disease(CD),but complex rectal fistula with abscess formation is rare.Tumor necrosis factor antagonists combined with percutaneous drainage or surgical intervention is optimal treatment for fistulizing CD with intraabdominal abscess.There is no study showing the efficacy of vedolizumab in such complicated condition.CASE SUMMARY A 47-year-old man has decompensated liver cirrhosis,Child B.He suffered from abdominal pain,bloody diarrhea,fever,and body weight loss.CD with rectoprostatic fistula,rectopresacral fistula,presacral abscess and cytomegalovirus(CMV)infection were noted.He received antibiotics,anti-viral therapy,transverse colostomy and vedolizumab treatment.Six months later,he had deep remission and complete fistula tracts closure.CONCLUSION Early vedolizumab and stool diversion are effective and safe in treating CD with complex rectal fistula with abscess formation.展开更多
BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are r...BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.展开更多
BACKGROUND Dual checkpoint inhibition improves response rates in treatment naive patients with metastatic melanoma compared to monotherapy.However,it confers a higher rate of toxicity,including immune-related colitis....BACKGROUND Dual checkpoint inhibition improves response rates in treatment naive patients with metastatic melanoma compared to monotherapy.However,it confers a higher rate of toxicity,including immune-related colitis.Steroids may not resolve symptoms in all cases.The use of vedolizumab,a humanized monoclonal antibody againstα4β7 integrin has proven effective in cases refractory to standard treatment.CASE SUMMARY We report the case of a 27-year-old female with Stage IVd metastatic melanoma treated with ipilimumab and nivolumab.She developed severe colitis refractory to methylprednisolone,infliximab and mycophenolate mofetil but responded to vedolizumab.CONCLUSION This case report supports vedolizumab use in severe immune related colitis refractory to standard immunosuppression.展开更多
BACKGROUND Immune check-point inhibitors-induced colitis(ICPIs-induced colitis) is one of the immune-related side effects.Steroids and Infliximab are commonly used to treat it.The patients of our report were treated b...BACKGROUND Immune check-point inhibitors-induced colitis(ICPIs-induced colitis) is one of the immune-related side effects.Steroids and Infliximab are commonly used to treat it.The patients of our report were treated by Vedolizumab.CASE SUMMARY The two patients went to the doctor with bloody stools and were treated by Sintilimab and Camrelizumab,respectively,for their malignant tumors.They were diagnosed as ICPIs-induced colitis based on endoscopic and histologic examination.The original immunotherapy was ceased while the anti-inflammatory therapy was introduced.The patients’ colitis symptoms disappeared after the treatment and no recurrence was found during the follow-up period.The unique feature about the case reports is that Vedolizumab combined with short-term corticosteroids had achieved good therapeutic effects.CONCLUSION For the symptoms of bloody diarrhea after the ICPIs treatment of cancer,the possibility of ICPIs-induced colitis should be considered.Vedolizumab combined with short-term corticosteroids may be appropriate for the treatment.展开更多
BACKGROUND Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with re...BACKGROUND Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.CASE SUMMARY A 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine,underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012.He developed chronic diarrhea in 2014,which was watery,30 per day and accompanied with blood and mucus affecting his quality of life.CONCLUSION Vedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.展开更多
Anorectal stenosis(ARS)is a rare complication of Crohn's disease(CD)and a risk factor for both fecal diversion(FD)and proctectomy,[1,2]especially in patients who failed anti-tumor necrosis factor-α(anti-TNF)thera...Anorectal stenosis(ARS)is a rare complication of Crohn's disease(CD)and a risk factor for both fecal diversion(FD)and proctectomy,[1,2]especially in patients who failed anti-tumor necrosis factor-α(anti-TNF)therapy)[3,4]Herein,we presented a case of a 17-year-old female diagnosed with CD at age 7,with inflammation located in the small bowel and colon(Paris classification:L3L4b).Due to corticosteroid dependency,infliximab with concomitant azathioprine was introduced at age 9 and discontinued two years after,because of the appearance of a 3 cm tumor-mass,which resembled a lymphoma,in the oral cavity.展开更多
Background:Vedolizumab was demonstrated to be safe and effective in adults with moderately to severely active inflammatory bowel disease(IBD)in clinical trials.However,there are limited data regarding its efficacy and...Background:Vedolizumab was demonstrated to be safe and effective in adults with moderately to severely active inflammatory bowel disease(IBD)in clinical trials.However,there are limited data regarding its efficacy and safety in elderly patients.Methods:This was a case-control study comparing the efficacy(measured by rates of mucosal healing and need for IBD surgery)and safety of vedolizumab in IBD among patients65 years of age(the elderly group)vs those<65 years(the control group).The two groups were matched individually on a 1:4 ratio based on gender and type of IBD.Conditional logistic regression was used for stratified analysis to calculate odds ratios and confidence intervals.Results:We included 25 IBD patients in the elderly group and 100 matched patients in the comparison group.Eighty patients had Crohn’s disease and 45 had ulcerative colitis.At baseline,the groups were comparable with regard to duration of IBD,prior anti-TNF therapy,and prior IBD surgery.The rate of mucosal healing on follow-up endoscopy was comparable between the elderly and control groups(50%vs 53%,P=0.507).Although more patients in the elderly group required IBD-related surgery while on vedolizumab,the difference did not reach statistical significance(40%vs 19%,P=0.282).Rates of vedolizumab-related adverse effects—rash,arthralgia,infections,infusion reactions,and dyspnea—were comparable between the two groups(all P>0.05).Conclusions:In a real-world setting,vedolizumab was demonstrated to have an efficacy and safety profile among elderly IBD patients that were comparable to younger controls.展开更多
Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-...Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-operative complications in patients who received vedolizumab—a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease—in clinical-trial and post-marketing settings.Methods:This post hoc analysis of safety data from GEMINI 1,GEMINI 2,and long-term safety studies included patients who had had colectomy or bowel surgery/resection.Data from the post-marketing Vedolizumab Global Safety Database were also analysed(data cutoff point:19 May 2016).Adverse events relating to post-operative complications were identified using Medical Dictionary for Regulatory Activities preferred terms.Results:Of 58 total surgeries in patients included in GEMINI 1 and GEMINI 2,post-operative complications were reported for 3/51 vedolizumab-treated patients(5.9%)and 1/7 placebo-treated patients(14.3%).In the long-term safety study,157/2,243 patients(7%)had colectomy or bowel surgery/resection;of these 157 patients who underwent surgery,11(7%)experienced a post-operative complication.Median time between last pre-operative vedolizumab dose and surgery was 23 days in GEMINI 1,20 days in GEMINI 2,and 39–40 days in the long-termsafety study.In the post-marketing setting,based on data covering approximately 46,978 patient-years of vedolizumab exposure,post-operative complications were reported in 19 patients.Conclusions:In clinical trials,complications of colectomy and bowel surgery/resection appeared infrequent,with minimal difference between vedolizumab and placebo.The frequency of post-operative complications in the post-marketing setting appears low.展开更多
Background:Our recent study showed the efficacy and safety of vedolizumab in the treatment of chronic antibioticrefractory pouchitis.However,there are no published studies on its efficacy and safety in Crohn’s diseas...Background:Our recent study showed the efficacy and safety of vedolizumab in the treatment of chronic antibioticrefractory pouchitis.However,there are no published studies on its efficacy and safety in Crohn’s disease(CD)of the pouch.The aim of this study was to assess the efficacy and safety of vedolizumab in those patients.Methods:This case series included all eligible patients with CD of the pouch from our prospectivelymaintained,IRB-approved Pouchitis Registry from 2015 to 2017.Disease activity in pouch patients can bemonitored using the modified Pouchitis Disease Activity Index(mPDAI).mPDAI is the 18-point pouchitis disease activity index consisting of three principal component scores:symptom(range,0–6 points),endoscopy,(range 0–6 points),and histology(range,2–6 points).Pre-and post-treatment(minimum 6 months)pouchoscopy and clinical visits were used to calculate mPDAI.Results:A total of 12 patients were included in this study,who had restorative proctocolectomy with ileal pouch anal anastomosis for medically refractory ulcerative colitis(UC).The mean age at the time of pre-colectomy diagnosis of UC was 25.0611.5 years.The mean current age was 41.0612.1 years,nine(75.0%)were female,three(25.0%)had smoked and eight(66.7%)had used anti-tumor necrosis factor agents prior to vedolizumab use.The mean duration of vedolizumab use was 1.066.4 years.There was a significant reduction in mPDAI symptom subscores after vedolizumab therapy(3.5061.93 vs 5.0860.79,P=0.015).The pre-and post-treatment mean endoscopy subscores were 1.2561.36 and 0.9161.50 in the afferent limb(P=0.583);2.5861.68 and 2.2762.05(P=0.701)in the pouch body;and 2.6761.93 and 2.0962.12(P=0.511)in the cuff,respectively.None of the patients experienced side effects throughout the vedolizumab therapy.Conclusion:The findings of our study suggests that vedolizumab appears to be effective and safe in reducing the symptoms in patients with CD of the pouch.展开更多
Background:Chronic antibiotic-refractory pouchitis(CARP)is a complication of ileal pouch-anal anastomosis(IPAA),which poses a therapeutic challenge.Vedolizumab,a gut-selective monoclonal antibody to the a4b7 of integr...Background:Chronic antibiotic-refractory pouchitis(CARP)is a complication of ileal pouch-anal anastomosis(IPAA),which poses a therapeutic challenge.Vedolizumab,a gut-selective monoclonal antibody to the a4b7 of integrin,has been used in such patients,but data on its efficacy are limited.Our aim was to assess the efficacy and safety of vedolizumab as induction therapy in CARP patients.Methods:In this single-center,historic cohort,patients with CARP who received vedolizumab between January 2015 to June 2017 were identified and analysed.Patients were included if they had active pouchitis with a total of modified pouch disease activity index(mPDAI)score5 or if unavailable clinician diagnosis of active pouchitis.Pre-treatment and at 3-month posttherapy pouchoscopy and clinical visits were used to calculate mPDAI.Results:A total of 19 patients were included in the study.The mean age was 26.7612.8 years,with 10(53%)males.Nine(47%)patients had been treated with anti-tumor necrosis factor(TNF)agents before colectomy and 10(53%)had anti-TNFs after colectomy and IPAA.Six(32%)patients had improvement in the mPDAI symptom subscores(P=0.031)and 14(74%)had improvement in both endoscopic and total mPDAI scores with a median change of-2 units(both P=0.031).Adverse events were noted only in two(11%)patients and four(21%)required surgery for CARP.Conclusions:Our study suggests that vedolizumab has efficacy and can be safely used for CARP patients.Larger studies with a higher number of patients are required to confirm these findings.展开更多
目的介绍1例维得利珠单抗(VDZ)致间质性肺炎的病例,汇总分析该药相关肺毒性的发生特点,为临床安全用药提供参考。方法从临床药师角度出发,回顾性分析1例VDZ致间质性肺炎患者的诊治过程,并进行不良反应相关性分析;检索中国知网、维普网、...目的介绍1例维得利珠单抗(VDZ)致间质性肺炎的病例,汇总分析该药相关肺毒性的发生特点,为临床安全用药提供参考。方法从临床药师角度出发,回顾性分析1例VDZ致间质性肺炎患者的诊治过程,并进行不良反应相关性分析;检索中国知网、维普网、PubMed、Web of Science等中英文数据库,对VDZ相关肺毒性的病例报道进行汇总分析。结果该患者在使用VDZ期间发生间质性肺炎,予抗菌药物经验性抗感染治疗无改善;停用VDZ并予甲泼尼龙治疗后,患者的症状及影像学检查均有改善但仍提示间质性肺炎。经Naranjo's不良反应评估量表评估并根据我国《药品不良反应报告和监测工作手册》判断,VDZ与间质性肺炎的关联性均为“很可能”。文献分析结果显示,纳入的29例患者(含本文报道的患者)中,男性19例、女性10例,平均年龄(49.24±17.06)岁;肺毒性主要包括VDZ相关性肺炎、嗜酸性粒细胞肺炎、肺肉芽肿或坏死性结节、间质性肺损伤等,多发生在用药后24周以内(58.62%),主要临床表现为咳嗽、呼吸困难、发热等;绝大多数患者经停药和/或给予糖皮质激素等治疗后好转或康复,1例患者因呼吸衰竭死亡。结论肺毒性为VDZ较罕见的不良反应,起病隐匿且症状无特异性。一旦患者出现咳嗽、呼吸困难等症状,临床应早期判断、及时停药,并给予糖皮质激素等对症治疗,以保障患者用药安全。展开更多
基金Supported by Takeda Australia,No.IISR-2016-101883.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.
基金Supported by Shenzhen Science and Technology Program,No.JCYJ20220530154013031Guangdong Province Health and Health Appropriate Technology Promotion Project,No.2023385Guangdong Province Grassroots Science Popularization Action Plan,No.20240205.
文摘BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.
基金Supported by Science and Technology Program of Liaoning Province,No.2013225303
文摘AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis(UC).METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on July 31, 2013. Inclusion criteria were:(1) Randomized controlled trial(RCT);(2) Patients treated for UC; and(3) Intervention was vedolizumab. The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, patient demographic information, response rate, remission rate, and adverse events. The primary outcome was clinical response rate, and the secondary outcomes were clinical remission rate and serious adverse events. Odds ratio(OR) with 95%CI were calculated for each outcome. RESULTS: Of 224 studies initially identified, three RCTs examining the use of vedolizumab meeting the inclusion criteria were included in the meta-analysis. All studies examined the use of vedolizumab at dosages ranging from 0.5 to 10 mg/kg body weight(one study used a standard dose of 300 mg). The follow-up periods were approximately 6 wk. The total number of patients in the intervention groups was 901, and in the control groups was 221. The mean age of the patients was approximately 41 years, and approximately half were males. The follow-up periods ranged from 43 d to 6 wk. The clinical response and remission rates were significantly higher for patients who received vedolizumab as compared to control patients(clinical response: OR = 2.69; 95%CI: 1.94-3.74, P < 0.001 and remission rate: OR = 2.72; 95%CI: 1.76-4.19, P < 0.001). Serious adverse events were not higher in patients that received vedolizumab.CONCLUSION: This analysis supports the use of vedolizumab for the treatment of UC.
文摘The biologic antitumor necrosis factor alpha(anti-TNFα) agents have revolutionised the treatment of inflammatorybowel disease(IBD). However,some patients experience primary nonresponse,loss of response,or intolerance. Therefore,introducing a newer class of therapy with a mechanism of action that acts on different inflammatory pathways involved in IBD pathogenesis is appealing. Vedolizumab is a fully humanised monoclonal antibody that selectively targets α4β7 integrin. Based on the results of the pivotal clinical GEMINI trials,vedolizumab was approved for the treatment of adult patients with moderately to severely active ulcerative colitis(UC) and Crohn's disease(CD) refractory or intolerant to either conventional therapy or TNFα inhibitors. This review describes the efficacy,safety,and tolerability of vedolizumab reported in both randomized,controlled,clinical trials and from real-world experience in patients with UC and CD in order to identify its place in treatment algorithms for IBD.
文摘BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)patients.AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.METHODS A retrospective review of Australian and Oxford,United Kingdom data for UC patients.Clinical response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were assessed.Cox regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing them.Safety outcomes were recorded.RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were included.The clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo respectively.Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 mo.CONCLUSION VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.
文摘BACKGROUND Fistula and intraabdominal abscess are common complications of Crohn’s disease(CD),but complex rectal fistula with abscess formation is rare.Tumor necrosis factor antagonists combined with percutaneous drainage or surgical intervention is optimal treatment for fistulizing CD with intraabdominal abscess.There is no study showing the efficacy of vedolizumab in such complicated condition.CASE SUMMARY A 47-year-old man has decompensated liver cirrhosis,Child B.He suffered from abdominal pain,bloody diarrhea,fever,and body weight loss.CD with rectoprostatic fistula,rectopresacral fistula,presacral abscess and cytomegalovirus(CMV)infection were noted.He received antibiotics,anti-viral therapy,transverse colostomy and vedolizumab treatment.Six months later,he had deep remission and complete fistula tracts closure.CONCLUSION Early vedolizumab and stool diversion are effective and safe in treating CD with complex rectal fistula with abscess formation.
基金Supported by the Dalian Municipal Science and Technology Innovation Foundation,No.2020JJ27SN072.
文摘BACKGROUND Vedolizumab,a newer class of integrin antagonist biological agents,has been applied to treat patients with moderate-to-severe Crohn’s disease(CD)and ulcerative colitis(UC),especially for patients who are refractory to traditional therapies and tumor necrosis factor antagonists.However,some rare but lifethreatening adverse effects warrant pharmacovigilance.We describe the first fatal case of vedolizumab-associated severe diffuse interstitial lung disease in China.CASE SUMMARY We present a case of new-onset diffuse parenchymal lung disease developing under treatment with vedolizumab in a patient with UC.After two doses of vedolizumab,he developed persistent fever and progressively worsening dyspnea.Extensive workups,including bronchoalveolar lavage,transbronchial lung biopsy and metagenomic next-generation sequencing,identified no infectious causes,and other potential causes(such as tumors and cardiogenic pulmonary edema)were also excluded.As a result,a diagnosis of vedolizumabrelated interstitial lung disease was established.Unfortunately,although corticosteroids and empiric antibiotics were administered,the patient eventually died of respiratory failure.CONCLUSION Vedolizumab-related interstitial lung disease in patients with UC is rare but potentially lethal.Gastroenterologists and pulmonologists should be aware of vedolizumab-related adverse drug reactions.
文摘BACKGROUND Dual checkpoint inhibition improves response rates in treatment naive patients with metastatic melanoma compared to monotherapy.However,it confers a higher rate of toxicity,including immune-related colitis.Steroids may not resolve symptoms in all cases.The use of vedolizumab,a humanized monoclonal antibody againstα4β7 integrin has proven effective in cases refractory to standard treatment.CASE SUMMARY We report the case of a 27-year-old female with Stage IVd metastatic melanoma treated with ipilimumab and nivolumab.She developed severe colitis refractory to methylprednisolone,infliximab and mycophenolate mofetil but responded to vedolizumab.CONCLUSION This case report supports vedolizumab use in severe immune related colitis refractory to standard immunosuppression.
文摘BACKGROUND Immune check-point inhibitors-induced colitis(ICPIs-induced colitis) is one of the immune-related side effects.Steroids and Infliximab are commonly used to treat it.The patients of our report were treated by Vedolizumab.CASE SUMMARY The two patients went to the doctor with bloody stools and were treated by Sintilimab and Camrelizumab,respectively,for their malignant tumors.They were diagnosed as ICPIs-induced colitis based on endoscopic and histologic examination.The original immunotherapy was ceased while the anti-inflammatory therapy was introduced.The patients’ colitis symptoms disappeared after the treatment and no recurrence was found during the follow-up period.The unique feature about the case reports is that Vedolizumab combined with short-term corticosteroids had achieved good therapeutic effects.CONCLUSION For the symptoms of bloody diarrhea after the ICPIs treatment of cancer,the possibility of ICPIs-induced colitis should be considered.Vedolizumab combined with short-term corticosteroids may be appropriate for the treatment.
文摘BACKGROUND Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.CASE SUMMARY A 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine,underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012.He developed chronic diarrhea in 2014,which was watery,30 per day and accompanied with blood and mucus affecting his quality of life.CONCLUSION Vedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.
文摘Anorectal stenosis(ARS)is a rare complication of Crohn's disease(CD)and a risk factor for both fecal diversion(FD)and proctectomy,[1,2]especially in patients who failed anti-tumor necrosis factor-α(anti-TNF)therapy)[3,4]Herein,we presented a case of a 17-year-old female diagnosed with CD at age 7,with inflammation located in the small bowel and colon(Paris classification:L3L4b).Due to corticosteroid dependency,infliximab with concomitant azathioprine was introduced at age 9 and discontinued two years after,because of the appearance of a 3 cm tumor-mass,which resembled a lymphoma,in the oral cavity.
文摘Background:Vedolizumab was demonstrated to be safe and effective in adults with moderately to severely active inflammatory bowel disease(IBD)in clinical trials.However,there are limited data regarding its efficacy and safety in elderly patients.Methods:This was a case-control study comparing the efficacy(measured by rates of mucosal healing and need for IBD surgery)and safety of vedolizumab in IBD among patients65 years of age(the elderly group)vs those<65 years(the control group).The two groups were matched individually on a 1:4 ratio based on gender and type of IBD.Conditional logistic regression was used for stratified analysis to calculate odds ratios and confidence intervals.Results:We included 25 IBD patients in the elderly group and 100 matched patients in the comparison group.Eighty patients had Crohn’s disease and 45 had ulcerative colitis.At baseline,the groups were comparable with regard to duration of IBD,prior anti-TNF therapy,and prior IBD surgery.The rate of mucosal healing on follow-up endoscopy was comparable between the elderly and control groups(50%vs 53%,P=0.507).Although more patients in the elderly group required IBD-related surgery while on vedolizumab,the difference did not reach statistical significance(40%vs 19%,P=0.282).Rates of vedolizumab-related adverse effects—rash,arthralgia,infections,infusion reactions,and dyspnea—were comparable between the two groups(all P>0.05).Conclusions:In a real-world setting,vedolizumab was demonstrated to have an efficacy and safety profile among elderly IBD patients that were comparable to younger controls.
基金This work was supported by Takeda Pharmaceutical Company Ltd.
文摘Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-operative complications in patients who received vedolizumab—a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease—in clinical-trial and post-marketing settings.Methods:This post hoc analysis of safety data from GEMINI 1,GEMINI 2,and long-term safety studies included patients who had had colectomy or bowel surgery/resection.Data from the post-marketing Vedolizumab Global Safety Database were also analysed(data cutoff point:19 May 2016).Adverse events relating to post-operative complications were identified using Medical Dictionary for Regulatory Activities preferred terms.Results:Of 58 total surgeries in patients included in GEMINI 1 and GEMINI 2,post-operative complications were reported for 3/51 vedolizumab-treated patients(5.9%)and 1/7 placebo-treated patients(14.3%).In the long-term safety study,157/2,243 patients(7%)had colectomy or bowel surgery/resection;of these 157 patients who underwent surgery,11(7%)experienced a post-operative complication.Median time between last pre-operative vedolizumab dose and surgery was 23 days in GEMINI 1,20 days in GEMINI 2,and 39–40 days in the long-termsafety study.In the post-marketing setting,based on data covering approximately 46,978 patient-years of vedolizumab exposure,post-operative complications were reported in 19 patients.Conclusions:In clinical trials,complications of colectomy and bowel surgery/resection appeared infrequent,with minimal difference between vedolizumab and placebo.The frequency of post-operative complications in the post-marketing setting appears low.
文摘Background:Our recent study showed the efficacy and safety of vedolizumab in the treatment of chronic antibioticrefractory pouchitis.However,there are no published studies on its efficacy and safety in Crohn’s disease(CD)of the pouch.The aim of this study was to assess the efficacy and safety of vedolizumab in those patients.Methods:This case series included all eligible patients with CD of the pouch from our prospectivelymaintained,IRB-approved Pouchitis Registry from 2015 to 2017.Disease activity in pouch patients can bemonitored using the modified Pouchitis Disease Activity Index(mPDAI).mPDAI is the 18-point pouchitis disease activity index consisting of three principal component scores:symptom(range,0–6 points),endoscopy,(range 0–6 points),and histology(range,2–6 points).Pre-and post-treatment(minimum 6 months)pouchoscopy and clinical visits were used to calculate mPDAI.Results:A total of 12 patients were included in this study,who had restorative proctocolectomy with ileal pouch anal anastomosis for medically refractory ulcerative colitis(UC).The mean age at the time of pre-colectomy diagnosis of UC was 25.0611.5 years.The mean current age was 41.0612.1 years,nine(75.0%)were female,three(25.0%)had smoked and eight(66.7%)had used anti-tumor necrosis factor agents prior to vedolizumab use.The mean duration of vedolizumab use was 1.066.4 years.There was a significant reduction in mPDAI symptom subscores after vedolizumab therapy(3.5061.93 vs 5.0860.79,P=0.015).The pre-and post-treatment mean endoscopy subscores were 1.2561.36 and 0.9161.50 in the afferent limb(P=0.583);2.5861.68 and 2.2762.05(P=0.701)in the pouch body;and 2.6761.93 and 2.0962.12(P=0.511)in the cuff,respectively.None of the patients experienced side effects throughout the vedolizumab therapy.Conclusion:The findings of our study suggests that vedolizumab appears to be effective and safe in reducing the symptoms in patients with CD of the pouch.
文摘Background:Chronic antibiotic-refractory pouchitis(CARP)is a complication of ileal pouch-anal anastomosis(IPAA),which poses a therapeutic challenge.Vedolizumab,a gut-selective monoclonal antibody to the a4b7 of integrin,has been used in such patients,but data on its efficacy are limited.Our aim was to assess the efficacy and safety of vedolizumab as induction therapy in CARP patients.Methods:In this single-center,historic cohort,patients with CARP who received vedolizumab between January 2015 to June 2017 were identified and analysed.Patients were included if they had active pouchitis with a total of modified pouch disease activity index(mPDAI)score5 or if unavailable clinician diagnosis of active pouchitis.Pre-treatment and at 3-month posttherapy pouchoscopy and clinical visits were used to calculate mPDAI.Results:A total of 19 patients were included in the study.The mean age was 26.7612.8 years,with 10(53%)males.Nine(47%)patients had been treated with anti-tumor necrosis factor(TNF)agents before colectomy and 10(53%)had anti-TNFs after colectomy and IPAA.Six(32%)patients had improvement in the mPDAI symptom subscores(P=0.031)and 14(74%)had improvement in both endoscopic and total mPDAI scores with a median change of-2 units(both P=0.031).Adverse events were noted only in two(11%)patients and four(21%)required surgery for CARP.Conclusions:Our study suggests that vedolizumab has efficacy and can be safely used for CARP patients.Larger studies with a higher number of patients are required to confirm these findings.
文摘目的介绍1例维得利珠单抗(VDZ)致间质性肺炎的病例,汇总分析该药相关肺毒性的发生特点,为临床安全用药提供参考。方法从临床药师角度出发,回顾性分析1例VDZ致间质性肺炎患者的诊治过程,并进行不良反应相关性分析;检索中国知网、维普网、PubMed、Web of Science等中英文数据库,对VDZ相关肺毒性的病例报道进行汇总分析。结果该患者在使用VDZ期间发生间质性肺炎,予抗菌药物经验性抗感染治疗无改善;停用VDZ并予甲泼尼龙治疗后,患者的症状及影像学检查均有改善但仍提示间质性肺炎。经Naranjo's不良反应评估量表评估并根据我国《药品不良反应报告和监测工作手册》判断,VDZ与间质性肺炎的关联性均为“很可能”。文献分析结果显示,纳入的29例患者(含本文报道的患者)中,男性19例、女性10例,平均年龄(49.24±17.06)岁;肺毒性主要包括VDZ相关性肺炎、嗜酸性粒细胞肺炎、肺肉芽肿或坏死性结节、间质性肺损伤等,多发生在用药后24周以内(58.62%),主要临床表现为咳嗽、呼吸困难、发热等;绝大多数患者经停药和/或给予糖皮质激素等治疗后好转或康复,1例患者因呼吸衰竭死亡。结论肺毒性为VDZ较罕见的不良反应,起病隐匿且症状无特异性。一旦患者出现咳嗽、呼吸困难等症状,临床应早期判断、及时停药,并给予糖皮质激素等对症治疗,以保障患者用药安全。