Effectiveness Of Vedolizumab In Patients Research Articles

P701 Evaluation of the effectiveness of vedolizumab in patients with Crohn's disease: a multicenter real-life study from Argentina

Abstract Background Vedolizumab (VDZ) is a gut-selective integrin inhibitor used to treat Crohn's disease (CD). Most of the information regarding real-life data on response to VDZ has been published from North America and Europe cohorts and there is scarce information from Latin America related to effectiveness of VDZ in patients with CD. The aims of this study were: i) to describe the clinical characteristics of patients with CD who received VDZ, ii) to know in which biologic line VDZ was indicated, and iii) to evaluate the clinical response at one year and the persistence of treatment during follow-up. Methods A retrospective multicenter study was conducted in 18 Argentinean centers. We included CD adult patients (age ≥18y) who started VDZ between 01/06/2015 and 31/10/2023 and completed at least VDZ induction. Baseline demographic characteristics, response at 12 months (m), need for optimization, and treatment persistence during follow-up were assessed. Logistic regression was used to evaluate predictors for response at 12m and treatment persistence. Results A total of 113 CD patients (57% male), mean age 52 years (range 18-87 years) were included. Colonic (47%) and ileal (29%) were the most frequent CD involvement. Inflammatory (68%) was the most frequent phenotype compared to stenosing (23%) and fistulizing (9%). Perianal involvement was present in 9% of patients. VDZ was indicated as first-line in 61 (54%) patients, second-line 31 (27.4%) patients, third line 17 (15%) patients, and fourth-line 4 (3.5%) patients. At 12 m of follow-up, clinical remission was observed in 37 (32.7%) patients and clinical response in 56 (49.6%) patients. Eighteen (15.9%) patients presented a lack of response/primary failure. Adverse effects leading to VDZ discontinuation prior to 12m occurred in 2 (1.8%) patients. Mean follow-up time in those patients that achieved clinical remission/response at 12m was 23 (SD 15) m. Thirty-five (37.6%) of those patients required dose optimization and 69 (74.2%) persisted on treatment during follow-up. Male sex (OR 2.93, 95%CI 1.04-8.26) and inflammatory phenotype (OR 5.37, 95%CI 1.16-24.9) were independent predictors for clinical response/remission at 12m. VDZ in first-line (OR 3, 95%CI 1.05-8.52) and inflammatory phenotype (OR 2.96, 95%CI 1.07-8.22) were independent predictors for treatment persistence in those patients that achieved clinical remission/response at 12m. Conclusion This is the first real-life multicenter study on the effectiveness of VZD in CD in Argentina and one of the largest in Latin America. VDZ showed an effective therapeutic option in a real-life setting. A higher efficacy was observed in males, inflammatory phenotype and in biologic-naïve patients.

Safety and Effectiveness of Vedolizumab in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim Analysis of a Japanese Post-Marketing Surveillance Study.

This ongoing post-marketing surveillance monitors the long-term safety and effectiveness of vedolizumab in routine clinical practice in patients with moderate-to-severe ulcerative colitis (UC) in Japan. This interim analysis assessed induction-phase data, covering the initial three doses of vedolizumab. Patients were enrolled via a web-based electronic data capture system from approximately 250 institutions. Incidence of adverse events and treatment responses were assessed by the physicians after the patient had received three doses of vedolizumab or when the drug was discontinued, whichever occurred first. Therapeutic response was defined as any treatment response, including remission or improvement of complete or partial Mayo score, and was assessed in the total and stratified patient populations according to prior tumor necrosis factor alpha (TNFα) inhibitor treatments and/or baseline partial Mayo score. The total incidence of adverse drug reactions (ADRs) was 4.10% (11/268). Common ADRs were dizziness, nausea, and arthralgia, each reported in 0.75% of patients (2/268). Serious ADRs were herpes zoster oticus and UC, each reported in 0.37% of patients (1/268). Therapeutic response was reported in 84.5% (218/258) of all patients, 85.8% (127/148) of TNFα inhibitor-naïve patients, and 82.7% (91/110) of TNFα inhibitor-experienced patients. Among patients with partial Mayo score of ≥ 4 at baseline, partial Mayo score remission in patients without or with prior TNFα inhibitor treatment was 62.5% (60/96) and 45.6% (36/79), respectively. The results confirm a safety and effectiveness profile of vedolizumab consistent with that observed in previous trials. JapicCTI-194603, NCT03824561.

S955 Effectiveness of Vedolizumab in Patients With Inflammatory Bowel Disease and Concomitant Primary Sclerosing Cholangitis

Introduction: Patients with concomitant primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are known to have a unique clinical phenotype (PSC-IBD), including higher expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in both liver and intestinal tissues. MADCAM-1 interacts with α4β7 integrin to allow access of lymphocytes to the intestinal mucosa and is inhibited by vedolizumab (VDZ). Although VDZ has not been shown to slow progression of PSC, little is known about its impact in intestinal inflammation of PSC-IBD patients. We aimed to report the effectiveness of VDZ in controlling intestinal inflammation in a large PSC-IBD cohort. Methods: We conducted a retrospective review of patients with PSC-IBD treated with VDZ from January 2009 to January 2019. Demographic, clinical, endoscopic, and radiologic data were abstracted at baseline, and at 6 and 12 months after initiation of VDZ. Outcomes of interest included: clinical response, radiologic response and healing, endoscopic response, mucosal healing, and histologic healing. Results: A total of 108 patients with PSC-IBD treated with VDZ were identified. The majority were male (66%), with median age of 45 years (range, 19 -83). The most common IBD subtype was ulcerative colitis (UC) (61.1%), followed by Crohn’s disease (CD) (33.3%), and indeterminate colitis (5.6%). Median disease duration at the start of VDZ was 8 years (range, 0-50), with ileocolonic CD (85.3%) and pancolitis (92.2%) as the predominant disease locations. Over three quarters of the cohort (79.6%) had previously failed other biologic therapy (Table). VDZ was most often dosed every 8 weeks (73.1%) and the median duration of VDZ therapy was 17.5 months (range, 2-66). Clinical response was 72.6% at 6 months and 77.1% at 1 year. Among patients who had follow-up endoscopy, endoscopic response was noted in 47.1% and 58.1% of the cases at 6 months and 1 year, respectively. Radiologic response at 6 months and 1 year was 32.4% and 38.9%, respectively. Radiology healing at 6 months and 1 year was 16.2% and 18.2%, respectively. Histologic healing at 6 months was 6.7% and 18.8% at 1 year. Conclusion: VDZ is effective in the management of intestinal inflammation in patients with PSC-IBD, with clinical and endoscopic outcomes at 1-year follow-up comparable to currently available clinical trials in non-PSC patients. Further studies comparing outcomes of PSC-IBD patients on VDZ to other biologic therapies are needed. Table 1. - Patient Demographics and Vedolizumab Outcomes Patient demographics N = 108 Male, n (%) 72 (66.7) Median age, years (range) 45 (19-83) Median disease duration, years (range) 8 (0-50) Prior use of other biologics, n (%) 86 (79.6) Combination therapy while on VDZ, n (%) Thiopurine/6MP/azathioprine 18 (17.3) Methotrexate 1 (1.0) IBD Subtype, n (%) CD 36 (33.3) UC 66 (61.1) Indeterminate colitis 6 (5.6) CD Location, n (%) Terminal ileum 0/34 (0) Colon 4/34 (11.8) Ileocolonic 29/34 (85.3) Upper GI 1/34 (2.9) Perianal disease, n (%) 9 (8.8) CD phenotype, n (%) Inflammatory 16/36 (44.4) Stricturing 14/36 (38.9) Penetrating 6/36 (16.7) UC extension, n (%) Proctitis 3/64 (4.7) Left sided colitis 2/64 (3.1) Pancolitis 59/64 (92.2) Bowel resection before VDZ, n (%) 45 (55.6) History of liver transplant, n (%) 33 (30.6) VDZ outcomes N = (108) Median duration of therapy, months (range) 17.5 (2.0-66.0) Drug dose frequency, n (%) Every 8 weeks 79 (73.1) Every 6 weeks 7 (6.5) Every 4 weeks 22 (20.4) VDZ discontinued indefinitely, n (%) 46 (43.0) Clinical response at 6 months, n (%) 74/102 (72.6) Clinical response at 1 year, n (%) 64/83 (77.1) Endoscopic response at 6 months, n (%) 24/51 (47.1) Endoscopic healing at 6 months, n (%) 8/55 (14.5) Endoscopic response at 1 year, n (%) 25/43 (58.1) Endoscopic healing at 1 year, n (%) 12/46 (26.1) Radiologic response at 6 months, n (%) 11/34 (32.4) Radiologic healing at 6 months, n (%) 6/37 (16.2) Radiologic response at 1 year, n (%) 7/18 (38.9) Radiologic healing at 1 year, n (%) 4/22 (18.2) Histologic healing at 6 months, n (%) 3/45 (6.7) Histologic healing at 1 year, n (%) 9/48 (18.8) Colectomy on VDZ, n (%) 16/108 (15.0)

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review

Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD. Data were collected from patients' medical records; criteria for extraction included no more than 1 allo-HCT and at least 1 dose of vedolizumab as treatment for SR GI aGVHD (ie, stage 1 to 4 GI aGVHD following ≥1 previous treatment regimen(s) containing ≥1mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites who had received 1 to 10 doses of vedolizumab 300mg i.v. (median 3 doses) as treatment for SR GI aGVHD. The overall response rate at 6 to 10 weeks after vedolizumab initiation was 64%, and OS at 6 months was 54%. There were 29 SAEs, including 12 infections; 3 SAEs were considered possibly related to vedolizumab, 2 of which were infections. Thirteen SAEs were fatal, 1 of which was possibly vedolizumab-related. There were 8 nonserious infections and 1 serious infection with confirmed GI origin in 8 patients; there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting from prospective trials are needed.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

Effectiveness of vedolizumab in real world clinical practice is unknown. To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. 521 patients were included (median follow-up 10months [interquartile range 5-18months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P<0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Vedolizumab in the treatment of chronic, antibiotic-dependent or refractory pouchitis.

The most common complication after ileal pouch anal anastomosis in up to 50% of patients is an acute pouchitis. The majority of patients respond to antibiotic treatment. However, 10%-15% develops chronic antibiotic-dependent or refractory pouchitis which is usually hard to treat. To evaluate the effectiveness of vedolizumab in patients with chronic pouchitis. Patients with chronic antibiotic-dependent or refractory pouchitis were treated with vedolizumab (300mg at week 0, 2, 6 and 10) in 10 IBD centres and retrospectively registered. Data were recorded until week 14 of vedolizumab treatment. In total 20 patients (12 male, median age 43years) were included for analysis. The effectiveness was measured using the Oresland Score (OS) at week 2, 6, 10 and 14 and the pouch disease activity index (PDAI) at week 0 and 14. The mean OS declined from 6.8 (range 2-12) to 3.4 (range 0-11). Concordantly, the mean PDAI after 14weeks of treatment dropped from 10 (range 5-18) to 3 (range 0-10). Only three patients reported moderate side effects. No serious side effects were recorded. In addition, symptomatic co-medication such as loperamide and tincture of opium could be terminated in 8 out of 12 patients as well as antibiotic treatment could be stopped in 17 out of 19 patients. Our data indicate that vedolizumab could be an option in the treatment of patients with chronic, antibiotic-dependent or refractory pouchitis.