Vedolizumab Initiation Research Articles

S731 Cytomegalovirus Colitis Is Rarely Observed After Initiation of Infliximab, Adalimumab, or Vedolizumab in Biologic-Naïve Patients With Ulcerative Colitis

S731 Cytomegalovirus Colitis Is Rarely Observed After Initiation of Infliximab, Adalimumab, or Vedolizumab in Biologic-Naïve Patients With Ulcerative Colitis

Herpes Zoster in a Patient With Ulcerative Colitis After Vedolizumab Initiation-Causal Link or Only Temporal Coincidence?

To the Editors, Herpes zoster results from the reactivation of latent varicella-zoster virus (VZV) in the cranial nerve or the dorsal root ganglia, with a higher rate in older persons or immunocompromised patients. Here, we report a case of herpes zoster eruption following the first dose of vedolizumab infusions in a 47-year-old man diagnosed with ulcerative colitis (UC). Previously, sulfasalazine and mesalazine failed to control UC activity in this patient. Given that no contraindications were found, vedolizumab was commenced in June 2021, with the patient also on mesalazine. Until this point, he had no previous episodes of herpes zoster eruption. However, 4 days after the first administration of vedolizumab, the patient developed a sore throat. On day 9 following the apparition of symptoms, scattered lesions on the right scapular area, right forearm, and fingers appeared, characterized by closely grouped papules and vesicles (Figure 1). The rash was preceded...

Efficacy of Vedolizumab in a Nationwide Cohort of Elderly Inflammatory Bowel Disease Patients.

The elderly inflammatory bowel disease (IBD) population has historically been under-represented in clinical trials, and data on the efficacy of biologic medications in elderly IBD patients are generally lacking. Our study aims to evaluate the efficacy of vedolizumab (VDZ) among elderly IBD patients and compare it with younger IBD patients in a nationwide population-based cohort of IBD patients. We conducted a retrospective cohort study of patients within the US national Veterans Affairs Healthcare System (VAHS). Patients were stratified into 2 groups based on age at the time of starting VDZ (60 years of age and older or younger than 60 years of age) with outcomes compared between the 2 groups. The primary outcome was steroid-free remission during the 6- to 12-month period after starting VDZ therapy among those patients who were on steroids when VDZ was started. There were 568 patients treated with VDZ, of whom 56.7% had Crohn's disease and 43.3% had ulcerative colitis. Among them, 316 patients were on steroids when VDZ was started. The percentage of patients who were on VDZ and off steroids during the 6- to 12-month period after VDZ initiation was 46.8% and 40.1% for the younger and elderly groups, respectively (P = 0.2374). Rates of hospitalization for an IBD-related reason within 1 year of VDZ start among the whole cohort were nearly identical in the younger and elderly groups (11.2% vs 11.3%, P = 0.9737). Rates of surgery for an IBD-related reason within 1 year of VDZ start were also similar between the young and elderly (3.9% vs 3.9%, P = 0.9851). In a nationwide real-world retrospective cohort study of elderly IBD patients, we found that the efficacy of VDZ was similar among younger and older IBD patients and comparable with the published data in clinical trials.

P288 Vedolizumab May Be An Effective Option For The Management Of Postoperative Recurrence Of Crohn’s Disease

Abstract Background The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn’s disease (CD) following ileocolonic resection is currently unknown. We aimed to assess the effectiveness of VDZ in this setting. Methods All consecutive CD patients with an available baseline colonoscopy at 6-12 months from the ileocolonic resection and treated with VDZ for the postoperative recurrence after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ. In patients with Rutgeerts score i0 or i1 at baseline, endoscopic success was defined by maintenance of Rutgeerts score i0 or i1; in patients with Rutgeerts score ≥ i2 at baseline, it was defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up. Results Seventy patients were included (median follow-up: 23.5 months). All 9 patients without endoscopic recurrence at baseline (Rutgeerts score i0 or i1) and available post-treatment colonoscopy maintained a Rutgeerts score i0 or i1 (treatment success: 100%). In patients with endoscopic recurrence (Rutgeerts score ≥ i2 at baseline), a reduction of at least one point in the Rutgeerts score was obtained in 20 out of 42 patients (47.6%). By combining the two subgroups, the overall endoscopic success was achieved in 29 out of 51 patients (56.9%). Furthermore, 14 out of 42 patients (33.3%) with endoscopic recurrence at baseline achieved a Rutgeerts score i0 or i1 at the subsequent colonoscopy. Clinical failure was reported in 13/70 patients (18.6%) at one year, and in 23/70 patients (32.9%) at the end of follow-up. A new resection was required in 7/70 patients (10.0%). Conclusion VDZ may be a therapeutic option for the management of postoperative recurrence of CD. Further studies are needed to confirm these results.

P347 Vedolizumab as first line biologic therapy in elderly patients with contraindications against anti-TNF therapy - A real-world nationwide cohort of patients with inflammatory bowel diseases

Abstract Background Data regarding the efficacy and safety of vedolizumab as the first line of biologic therapy for elderly patients with ulcerative colitis (UC) and Crohn’s disease (CD) or patients with contraindications against anti-tumor necrosis factor antagonists (anti-TNFs) are scarce. Therefore, we aimed to investigate the short and long-term efficacy and safety of vedolizumab in patients with bio-naïve UC and CD stratified according to age. Methods A Danish nationwide cohort study was conducted between November 2014 and November 2019, including all bio-naïve patients receiving vedolizumab. The primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission defined as clinical remission at week 14 through week 52. Elderly patients were defined as patients aged 60 years or older at initiation of vedolizumab. Results The study included 56 patients (UC: 31 (55.4%), CD: 25 (44.6%)) with 15 (60.0%) and nine (47.4%) elderly patients with UC and CD, respectively. Elderly patients with UC and CD experienced higher rates of early response, remission, and steroid-free clinical remission, which, however, did not reach statistical significance (Figures 1 and 2). However, elderly patients with CD had similar long-term response as compared with younger patients. In the overall study population, lack of remission at week 52 was associated with female gender (p=0.01) in UC and ileal CD (p=0.03). Discontinuation due to primary non-response occurred in 20.0% and 5.3%, while rates of secondary loss of response were 12.0% and 5.3% after 26 weeks and 52 weeks, respectively. Only one UC patient, who developed a serious infection, experienced a serious adverse event during treatment with vedolizumab. However, mild adverse events were experienced by 35.5% and 8.0% of patients with UC and CD, respectively. As shown in Table 1, elderly patients experienced adverse events similar to the corresponding younger patients. Conclusion Vedolizumab is effective for induction of short and long-term sustained clinical remission in bio-naïve elderly and younger UC and CD patients with contraindications to anti-TNFs.

P425 Real-world evidence on effectiveness and safety of vedolizumab therapy for inflammatory bowel disease in Taiwan: Results from the TSIBD registry (VIOLET Study)

Abstract Background GEMINI trials and real-world studies in Western population have demonstrated the effectiveness and safety of vedolizumab (VDZ) for IBD. However, long-term real-world evidence of VDZ in Asian populations remains limited. This study aimed to investigate the effectiveness and safety of VDZ in Taiwan CD and UC patients, and the IBD relapse after VDZ discontinuation. Methods Data were prospectively collected (January 2018-May 2020) from the Taiwan Society of IBD (TSIBD) registry, one of the largest real-world Asian IBD cohorts. Patients (>18 years old) receiving ≥1 dose of VDZ with up to a 1-year follow-up period were analyzed. Effectiveness at 6 month and 1 year including clinical response (CRS), clinical remission (CRM), steroid-free remission (SRM) and mucosal healing (MH);and safety outcome were analyzed descriptively. IBD relapse after VDZ treatment discontinuation was assessed since the reimbursement period in Taiwan is limited due to drug holiday required by government. Results A total of 274 patients (CD:127, UC:147) were included. At VDZ initiation, average [SD] age (year): 33.4 [14.6] in CD and 42.4 [14.3] in UC; median disease duration (years): 3.1 in CD and 3.9 in UC; 50.4% of CD and 70.7% of UC patients were biologics (bio)-naïve. Treatment effectiveness was analyzed (Figure 1-4). At 6 months, effectiveness in the CD bio-naïve group was significantly higher than the bio-exposed patients in CRS (67.4% vs 43.9%, p=0.047), CRM (62.8% vs 39.0%, p=0.025), and SRM (43.3% vs 4.3%, p=0.001), respectively. At 1 year, the CD bio-naïve group had higher CRS (82.1% vs 60.7%, p=0.026) than the bio-exposed group. There was no difference in effectiveness between bio-naïve and bio-exposed groups in UC at both 6 months and 1 year. Three patients (1.1%) reported serious infections (respiratory infection, intractable infection with underlying myelodysplastic syndrome and intestinal perforation due to endoscopy) and two (0.7%) had infusion-related reactions. No malignancies or hepatic injuries were reported. After limited treatment up to one year due to reimbursement, 58% (54/93) of patients had IBD relapse (CD: 27 [62.8%], UC: 27 [54%]). After cessation of VDZ, the mean [SD] time to IBD relapse was 5.5 [4.0] months in CD, and 5.8 [5.7] months for UC. Conclusion This study has shown the effectiveness and safety of VDZ therapy for Taiwan IBD patients. Better outcomes were observed in bio-naïve CD patients, whereas bio-naïve and bio-exposed UC patients have comparable outcomes. After a limited VDZ treatment duration, over one-half of patients had IBD relapse, with the majority occurring within 5 months of VDZ discontinuation. These data suggest that continued VDZ therapy would benefit the majority of IBD patients in Taiwan.

DOP60 Simplified rules to identify bio-naïve patients with Crohn’s Disease with higher likelihood of clinical remission when initiating vedolizumab versus anti-TNFα therapies: Analysis of EVOLVE study data

Abstract Background Previously, we identified subsets of biologic-naïve patients (pts) with Crohn’s disease (CD) from the EVOLVE study who had higher rates of clinical remission (CR) [Fig 1] when initiating vedolizumab (VDZ) vs anti-TNFα treatment, using prediction models based on multiple baseline characteristics.1,2 To aid use in practice, we investigated whether these subsets could be identified using simpler rules based on fewer baseline characteristics. Methods Using data from EVOLVE, we used recursive partitioning and regression tree (RPART) classification to predict membership in the previously identified higher CR subsets for VDZ. The RPART algorithm repeatedly splits data, based on baseline predictors (demographics, prior treatments, clinical characteristics at treatment initiation, Charlson comorbidity index, prior extraintestinal manifestations [EIMs], and prior healthcare resource use). At each split, the predictor and its value as chosen by the algorithm to split the data were those that maximized the number of pts classified correctly. Simplified rules were developed from the resulting RPART decision trees. Analyses of the treatment effect of VDZ vs anti-TNFα were conducted in the subsets of pts identified by each rule. Results Pts with data on CR and candidate predictors were included (VDZ [n=195]; anti-TNFα [n=245]). Three simplified rules (A, B, & C) were identified (Table 1). Pt characteristics included in the rules (exacerbation ongoing at treatment initiation, no emergency department/emergency room (ED/ER) visits prior to treatment initiation, no fistulae at most recent assessment prior to treatment initiation, pre-initiation disease behaviour) were among the main predictors of CR in VDZ pts identified previously. Pts identified by Rule A comprised 32% of the EVOLVE population, and were those who 1) had an exacerbation ongoing at index, 2) did not have ED/ER visits prior to initiation and 3) had pre-initiation disease behaviour classified as other than stricturing with/without perianal disease. Among these pts, median time to CR for VDZ and anti-TNFα pts were 6.7 and 18.1 months, respectively (unadjusted log-rank p<0.001), and the adjusted hazard ratio (HR) of CR for VDZ vs anti-TNFα was 2.9 (95% CI: 1.7, 5.0). Rules B & C identified larger subsets in which VDZ vs anti-TNFα treatment differences were smaller but still statistically significant. Conclusion Simple rules were developed to identify biologic-naïve, CD pts in whom VDZ initiation appeared to have a larger effect on CR relative to anti-TNFα initiation. Validation of these rules in other data sources is important to confirm these findings; if validated, these simplified rules can inform targeting of treatment and optimization of outcomes for pts with CD treated with VDZ.

P406 A retrospective analysis of the efficacy of vedolizumab on extra-intestinal manifestations in patients with inflammatory bowel disease across five European countries

Abstract Background Vedolizumab is an α4β7 integrin monoclonal antibody indicated for moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC). There are limited data on how vedolizumab impacts extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD). The aim of the study was to analyse the effect of vedolizumab on EIM in a real-world cohort of IBD patients. Methods A multicentre retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands and Switzerland. Adult patients with moderately to severely active IBD and concurrent active EIM with at least 6 months follow-up after vedolizumab initiation (index date) were enrolled. Improvement of EIM was defined as absence of symptoms (resolution) or partial response (reduction of symptoms). Results 99 patients were included (UC: 44, CD: 55); the majority of active EIM at index were musculoskeletal (Table 1). Median disease duration at index was 9 (IQR: 3-19) years and 77% of patients had been exposed to 1+ biologic. Overall, after 6 and 12 months of vedolizumab, 37% and 50% of EIM respectively were reported as improved, 22%, 25% as stable (no change) and 1% and 3% as worsened (Table 2), missing values were 5% and 4%, respectively. Median time since first EIM improvement was 0.5 months (Figure 1). At 6 and 12 months, 48% (10/21) and 33% (6/18) of patients experienced clinical response/remission of their IBD, respectively. Vedolizumab treatment persistence at 12 months was 83% overall (Figure 2). Adverse Events were reported for 18% patients; 96% of them non-serious. Conclusion Vedolizumab treatment was associated with an improvement in 37% and 50% of EIM at 6 and 12 months, respectively, in a real-world IBD cohort.

P370 Concomitant azathioprine prevents new-onset arthralgia after initiation of vedolizumab: A retrospective cohort study

Abstract Background Vedolizumab is a monoclonal antibody against the gut-homing integrin α4β7 that is being used for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). An increasing number of studies have reported new onset or reactivation of extra-intestinal manifestations (EIMs), among which arthralgia is the most prominent. Methods We aimed to study the incidence, characteristics and possible predictors of arthralgia development in patients under treatment with Vedolizumab, in a retrospective cohort study in 3 IBD centers in Athens, Greece. UC and CD patients treated with Vedolizumab (n=115, men=50.4%, UC=70.4%, median duration of follow-up=9 months) or Infliximab (n=93, men=69.9%, UC=29%, median duration of follow-up=29.1 months) were recruited. For each participant the entry point for the study was the first day of drug administration while the endpoint was either the day of arthralgia occurrence, the day of drug discontinuation or the day of the last interview if the patient was still receiving the drug. The SPSS-23 statistical program was used for analysis. Results Patients under Vedolizumab were at higher risk for new-onset (HR=4.76, P=0.001) and recurrent (HR=5.41, P=0.003) arthralgia compared to patients under Infliximab. New-onset arthralgia occurred in 20.9% while recurrent in 37.8% of 45 patients with a history of articular EIM. New-onset and recurrent arthralgias differed in certain characteristics. New-onset arthralgia involved peripheral joints in 91.7%, was milder, occurred shortly after Vedolizumab initiation (median drug exposure= 3 months, IQR=5 months) in patients in remission and remitted in 50% of cases. In multivariate Cox’s proportional-hazards model new-onset arthralgia was significantly associated with extensive colitis (HR=2.91, 95%CI=1.04-8.12). Of 15 patients with concomitant treatment of azathioprine no one manifested new-onset arthralgia (X2 P= 0.03, Fisher’s exact test P=0.038). Similarly, no patient with a history of appendectomy manifested new-onset arthralgia (n=12, X2 P= 0.067, Fisher’s exact test P=0.12). No predictors were identified for recurrent arthralgia. No patients discontinued vedolizumab due to arthralgia. Conclusion Vedolizumab treatment may be associated with the temporal manifestation of arthralgias. Patients under Vedolizumab with extensive ulcerative colitis have a higher risk of developing new-onset arthralgia, whereas, concomitant treatment with azathioprine and a history of appendectomy appears to have a prophylactic effect. This effect could be indicative of a distinct pathophysiological lymphocyte-mediated mechanism.

P584 Mucosal Eosinophilia is an Independent Predictor of Vedolizumab Effectiveness in Ulcerative Colitis

Abstract Background Ulcerative Colitis (UC) is characterized by intestinal inflammation with chronic inflammatory features. Along with the typical neutrophil-predominant inflammation, there has been growing understanding of the role of eosinophils in UC and the potential therapeutic benefit of Vedolizumab (VDZ) in those cases. VDZ blocks gastrointestinal homing of T lymphocytes and eosinophil recruitment to the intestinal mucosa via blocking α4β7 which plays a major role in eosinophils localization to the intestinal mucosa. We aimed to assess whether mucosal eosinophilia can predict response to VDZ. Methods A retrospective study in a single IBD center. Active UC patients who were initiated on VDZ were identified. All patients had at least one documented encounter of VDZ infusion, colonoscopy prior to initiation of VDZ and afterwards with mucosal biopsies at both time points. The endoscopic activity was scored using Mayo endoscopic subscore (MES) with remission as MES 0 or 1. Clinical response was assessed using Physician’s Global Assessment (PGA) as no response, partial or complete clinical response and clinical remission. Histology was reported by an expert GI pathologist and the response was assessed as none, partial or complete. Mucosal eosinophilia was graded at initial and follow-up biopsies as not conspicuous vs. conspicuous with predominance of eosinophils (>100 eosinophils in at least 2 hpf). Eosinophil activity defined as presence of at least 1 of the 3 histologic features: eosinophilic microabscesses, eosinophilic cryptitis, or degranulated eosinophils Results 107 UC patients were included in the study with a mean age of 44.9 years, majority were males (N = 61, 55.5%), Caucasians (N = 96, 87.3%) and with pancolonic location (N = 100, 90.9%). Mean disease duration was 11.3 yrs (SD, 8.6). 55.5% of patients had prior aTNF exposure. Clinical remission was observed in (N = 63, 57.3%) and endoscopic remission (N = 73, 66.4%) after initiating VDZ. Complete histological response was observed in (N=50, 46.7%). Baseline characteristics based on endoscopic remission is shown where male sex, disease location and the proportion of patients with conspicuous eosinophils with abnormal activity in mucosal biopsies as well as no improvement in eosinophil activity compared to pre-treatment biopsies is greater among those not in endoscopic remission. In a stepwise backward logistic regression model including sex and disease location, improvement in abnormal eosinophilic activity was independently associated with increased odds of endoscopic remission after initiating vedolizumab (OR 4.3; CI, 1.1 - 16.4, p = 0.03). Conclusion In ulcerative colitis, change in mucosal eosinophilia after initiating VDZ was an independent predictor of endoscopic remission with VDZ.

P276 Influence of vedolizumab on extraintestinal manifestations in Inflammatory Bowel Disease: a nationwide multicenter study of the GETECCU Eneida registry

Abstract Background Evidence regarding vedolizumab (VDZ) influence on extraintestinal manifestations (EIMs) in inflammatory bowel disease patients (IBD) is scarce. Our aim was to analyze the effectiveness of VDZ in pre-existing EIMs and the occurrence of de novo EIMs during VDZ therapy in IBD. Methods We performed an observational, multicenter, retrospective cohort study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified 551 patients from 20 centers. The co-primary outcomes were to evaluate the response of EIMs to VDZ and to assess the frequency of de novo EIMs during therapy. Secondary outcomes were to analyze associated factors with EIMs response to VDZ, time from VDZ initiation to occurrence of de novo EIMs and the discontinuation rate of VDZ because of worsening/de novo EIMs. Response and worsening of IBD and EIMs were defined by clinical and laboratory criteria according to the physician’s assessment. Results The median age of the cohort was 49.7 years (IQR 38-60), 50.8% were female, 50.8% had Crohn’s disease and 90.4% had prior biologic exposure (more than 1 biologic drug in 57.9%). At baseline 133 patients (24.1%) had pre-existing EIMs of whom 21 showed more than 1 EIM; 76.7% of EIMs were articular and 31% cutaneous. Regarding 77 patients with active EIMs at baseline, response of EIMs to VDZ at 3 months was observed in 23 (29.9%), worsening in 13 (16.9%) and no change in 41 (53.2%). Response rates for active EIMs were 35.4% for peripheral arthritis (PA), 11.8% for axial arthropathy (AA), 35.7% for cutaneous EIMs and 33.3% for ocular EIMs. Response of IBD at 3 months was the only associated factor with response of EIMs to VDZ (OR=3.72; CI 95% [1.08-12.83]). Among 56 patients with inactive EIMs at baseline, worsening of EIMs was observed in 5 patients after 12 months of VDZ therapy (13.5%) (3 cases of PA and 2 of AA). During follow-up 25 patients (4.5%) developed 27 de novo EIMs (17 cases of PA, 4 of AA, 4 of erythema nodosum, 1 of pyoderma gangrenosum and 1 of episcleritis). Median time from VDZ initiation to onset of de novo EIMs was 244 days (IQR 115-693). Presence of more than 1 pre-existing EIM was the only associated factor with de novo EIM onset during first year of VDZ therapy (OR=14.5; 95% CI [3.3-62]). Worsening of pre-existing EIMs or de novo EIMs was the cause of VDZ discontinuation in 15 patients (5.8% of all patients who discontinued VDZ). Conclusion VDZ achieved clinical response of active EIMs in nearly a third of patients after 3 months of therapy, being the response of IBD to VDZ the only associated factor. Worsening of inactive EIMs or de novo EIMs during VDZ therapy was infrequent.

P223 Degree of Histological Activity is not Associated with Vedolizumab Therapy Outcome in Ulcerative Colitis

Abstract Background Histological inflammation is known to be associated with increased risk of disease relapse in patients with ulcerative colitis (UC). Vedolizumab (VDZ) is a gut selective anti-integrin which inhibits intestinal immune cell-trafficking. Whether the degree of histological activity at the time of VDZ therapy initiation is associated with therapy outcome is not known. We aimed to determine if there is an association between histological activity at the time of VDZ initiation and outcome of therapy. Methods A retrospective review was performed to identify UC patients treated with VDZ who had undergone an endoscopic assessment prior to therapy commencement. Baseline demographic data, information on therapy outcome and Mayo endoscopic sub score (MES) was collected for all patients. Endoscopic biopsies were retrieved and were scored for histological activity using the Geboes Score (GS). For Kaplan Meir analyses of primary endpoint, the cohort was dichotomised around a GS grade of 5. Primary endpoint was VDZ therapy outcome defined as persistence on VDZ therapy over time. Secondary endpoints included association between GS and MES and the association between a combined endoscopic and histological endpoint (MES = 3 & GS grade 5) and VDZ therapy outcome. Results 33 patients were included [median age 44.3 years (range 17.2 -84.3); 36% male gender]. 24%, 43% and 33% of the cohort had proctitis, left-sided colitis and extensive colitis respectively. 67% of subjects had prior anti-TNF exposure. Median time from endoscopy to commencement of VDZ was 9 weeks. Median study follow-up was 68 weeks (range 6.1 – 228.7). 3%, 21%, 42% and 33% had MES of 0, 1, 2 and 3 respectively. GS grade was significantly associated with MES (p = 0.04) (Figure 1). GS grade was not associated with time to discontinuation of VDZ (p=0.64) (Figure 2). Combined endoscopic and histological endpoint was not associated with time to discontinuation of VDZ (p=0.43) (Figure 3). The presence of lamina propria eosinophils was not associated with time to discontinuation of VDZ (p=0.92). Conclusion GS grade is associated significantly with MES which has been demonstrated previously. Neither histological activity alone nor in combination endoscopic activity were associated with outcome of VDZ therapy. Assessment of histological activity does not appear to provide additional information when selecting patients for VDZ therapy.

Prior Immunogenicity to Anti-TNF Biologics Is Not Associated with Increased Anti-drug Antibodies to Vedolizumab or Ustekinumab

Patients with inflammatory bowel disease (IBD) on biologic therapy may lose response to anti-tumor necrosis factor agents (anti-TNFs) due to the development of anti-drug antibodies (ADAs). A history of anti-TNF ADA increases the risk of developing ADA to subsequent anti-TNFs; however, it is not known whether ADA to anti-TNFs increases the risk of ADA development to vedolizumab (VDZ) or ustekinumab (UST). We aimed to investigate whether prior history of ADA to anti-TNF increases the risk of ADA to VDZ and UST. We conducted a retrospective cohort study of patients at a tertiary care IBD center over the course of four years who had previous anti-TNF drug and ADA level data during maintenance treatment and subsequent VDZ or UST drug and antibody levels, all collected as standard of care. The primary outcome was the rate of ADA development to VDZ and UST in patients with and without prior anti-TNF immunogenicity. Descriptive statistics summarized the data and univariate tested associations. Of the 152 IBD patients analyzed, 41 (27%) had a history of previous anti-TNF ADA with 22 (53.7%) having simultaneously undetectable anti-TNF drug levels. There was no significant difference in the rates of ustekinumab and vedolizumab ADA development between patients with prior ADA and patients without prior ADA (1/41 [2.7%] vs 1/111 [0.9%]; p = 0.54). There was also no difference in concomitant immunomodulator use with ustekinumab or vedolizumab initiation in patients with or without prior ADA (13/41 [31.7%] vs 31/111 [27.9%], p = 0.84). Neither patient who developed ADA to VDZ or UST was on concomitant immunomodulator at drug initiation, and both patients had detectable drug levels at the time of antibody detection. We observed that prior immunogenicity to anti-TNF agents does not confer an increased risk of immunogenicity to ustekinumab or vedolizumab. Our data support the use of vedolizumab or ustekinumab as monotherapy for the treatment of IBD.

Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients.

Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases. In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described. A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n = 4), unifocal (n = 6), and enthesitis/synovitis/dactylitis (n = 1). The mean duration of symptoms was 46 weeks (range 6-119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications. A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy.

The real-world outcomes of vedolizumab in patients with ulcerative colitis in Korea: a multicenter retrospective study.

Aim:This study examined the real-world effectiveness and safety outcomes of vedolizumab in ulcerative colitis (UC) patients who had failed anti-tumor necrosis factor (anti-TNF) therapy in Korea.Methods:A retrospective chart review study was conducted in adults with moderate to severely active UC who had failed anti-TNF agents and subsequently received vedolizumab. Clinical response and clinical remission at week 6 and 14 after vedolizumab initiation was evaluated. Safety outcomes were also reported. Outcome rates were compared with a matched sub-cohort derived from the open-label sub-cohort of the GEMINI 1 trial using the optimal matching method.Results:A total of 105 patients (mean age, 45.3 years; 63.8% male) were included. At week 6, 55.8% (n = 43/77) achieved a clinical response and 18.2% (n = 14/77) achieved clinical remission. At week 14, 73.2% (n = 52/71) achieved a clinical response and 39.4% (n = 28/71) achieved clinical remission. When non-response imputation was used, the clinical response rate at week 6 and week 14 were 40.1% (n = 43/105) and 49.5% (n = 52/105) respectively. Of the 105 patients, 16 (15.2%) experienced at least one adverse event. The matched analysis showed that the clinical response rate at week 6 was higher in the matched sub-cohort of this study (24/47, 51.1%) versus the matched sub-cohort from the GEMINI 1 open-label cohort (12/47, 34.3%, p = 0.019). The clinical remission rates at week 6 were similar (7/47, 14.9% versus 9/47, 19.1%, p = 0.785).Conclusions:In the real-world setting, vedolizumab is effective and well tolerated within the first 14 weeks of use in Korea. The proportion of patients experiencing clinical response and clinical remission at 6 and 14 weeks appeared to be largely consistent with that observed in real-world studies from other regions and populations.

The Impact of Vedolizumab on Pre-Existing Extraintestinal Manifestations of Inflammatory Bowel Disease: A Multicenter Study.

There are limited data on how vedolizumab (VDZ) impacts extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). The aim of this study was to determine the clinical outcomes of EIMs after initiation of VDZ for patients with IBD. A multicenter retrospective study of patients with IBD who received at least 1 dose of VDZ between January 1, 2014 and August 1, 2019 was conducted. The primary outcome was the rate of worsening EIMs after VDZ. Secondary outcomes were factors associated with worsening EIMs and peripheral arthritis (PA) specifically after VDZ. A total of 201 patients with IBD (72.6% with Crohn disease; median age 38.4 years (interquartile range, 29-52.4 years); 62.2% female) with EIMs before VDZ treatment were included. The most common type of EIM before VDZ was peripheral arthritis (PA) (68.2%). Worsening of EIMs after VDZ occurred in 34.8% of patients. There were no statistically significant differences between the worsened EIM (n = 70) and the stable EIM (n = 131) groups in term of age, IBD subtype, or previous and current medical therapy. We found that PA was significantly more common in the worsening EIM group (84.3% vs 59.6%; P < 0.01). Worsening of EIMs was associated with a higher rate of discontinuation of VDZ during study follow-up when compared with the stable EIM group (61.4% vs 44%; P = 0.02). Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients. Almost one-third of patients had worsening EIMs after VDZ, which resulted in VDZ discontinuation in approximately 10% of patients. Previous biologic use or concurrent immunosuppressant or corticosteroid therapy did not predict EIM course after VDZ.

Experiences of using vedolizumab in the treatment of inflammatory bowel disease in the East Midlands UK – a retrospective observational study

Purpose Clinical trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn’s disease (CD). Further real-world data is needed to inform clinical practice. The primary outcome was to assess corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers, concomitant drug use, endoscopic remission, surgical intervention, hospital admissions and adverse events. Materials and methods A multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across seven UK hospitals 1/11/14-30/11/16. Clinical disease activity was assessed using the partial Mayo Scores (pMS) and Harvey Bradshaw Index (HBI). Clinical remission was defined as HBI ≤4 or pMS <2 with a combined stool frequency and rectal bleeding sub score of ≤1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI. Results One hundred ninety-two patients were included in the final analysis. 45% of UC and 10% of CD patients were anti-TNF naive. Over the observation period corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Time to corticosteroid free remission for UC and CD was 17.6 [IQR: 8.7–29.6] and 14.1 [QR: 6.0–21.7] weeks, respectively. Time to clinical response for UC was 9.4 [IQR: 5.7–15.4] and CD was 9.5 [IQR: 6.1–18.2] weeks. There was a substantial decrease in the concomitant use of immunomodulators and a similar decrease in concomitant corticosteroid use over the study period. Conclusions Results in this predominately anti-TNF experienced population mirror other published real-world data, demonstrating good clinical effectiveness and a comparable safety profile.

Vedolizumab for the Induction of Remission in Treatment-refractory Microscopic Colitis in a Pediatric Patient.

Vedolizumab for the Induction of Remission in Treatment-refractory Microscopic Colitis in a Pediatric Patient.

Predicting Response to Vedolizumab in Inflammatory Bowel Disease.

Vedolizumab is known to be safe, well-tolerated, and effective. However, as personalization becomes an increasingly important aspect of IBD care and in lieu of guidelines to inform clinicians on positioning of biologics, there is a need to reliably predict response to inform patient preferences and shared decision-making. Recent data from clinical trials and real-world evidence have elucidated predictors of clinical and endoscopic response while providing the framework to establish predictive models. Current models are able to predict that those patients with less severe disease, without prior biologic exposure and who demonstrate early response to VDZ have the highest rates of durable clinical and endoscopic response and remission. When incorporating these models into clinical practice, clinicians will be able to identify those patients who are likely to respond before drug initiation as well as early non-responders and response latency after initiation of vedolizumab. In a shift toward personalization of medicine in IBD, the ability of predictive models for vedolizumab to aid pre-biologic and early management will inform both clinician and patient. Ideally this will provide both a personalized and more cost-effective approach, though further studies in cost-analysis in this framework are needed. Though current models are comprehensive of existing data, future research on microbial and translational biomarkers will be additive and necessary to provide full personalization of treatment.

P445 Efficacy and safety of induction therapy with calcineurin inhibitors followed by maintenance therapy with vedolizumab in severe ulcerative colitis: a large patient cohort with long-term follow-up

Abstract Background The options for the medical management of patients with severe ulcerative colitis failing IV steroids are limited and include the calcineurin inhibitors cyclosporin or tacrolimus, especially in patients who had previously failed anti-TNF agents. Following induction therapy with a calcineurin inhibitor, transitioning to vedolizumab as maintenance therapy could be an option. We report on the largest cohort of patients successfully induced with calcineurin inhibitors who were then transitioned to vedolizumab maintenance therapy. Methods We performed a retrospective observational study of adult ulcerative colitis patients followed at the University of Chicago Inflammatory Bowel Disease Center. Patients with severe steroid-refractory ulcerative colitis were included if they received a calcineurin inhibitor (ciclosporin or tacrolimus) as induction therapy followed by maintenance therapy with vedolizumab between January 2014 and December 2018. Patients who had a follow-up of fewer than three months were excluded. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14. Results A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with calcineurin inhibitors for severe steroid-refractory colitis. Truelove and Witts criteria for Acute Severe Ulcerative Colitis were fulfilled in 77% of patients, and 97% of patients had moderate to severe endoscopic disease. Patients were followed for a median time of 25 months (IQR 16–36). Colectomy free survival rates from vedolizumab initiation were 67% at one year and 55% at two years (Figure 1, Panel A). At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At one and two years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab, respectively (Figure 1, Panel B). Vedolizumab was dose escalated to infusions every four weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1–8.2). No serious adverse events were recorded in our patient cohort. Conclusion Transitioning to vedolizumab following induction of remission with calcineurin inhibitors is effective and safe. Such a treatment strategy should be considered in patients with severe steroid-refractory ulcerative colitis, especially in cases of previous anti-TNF failure.