Use Of Vedolizumab Research Articles

757 Histologic Improvement With Vedolizumab vs. Adalimumab in Ulcerative Colitis: Results From VARSITY

INTRODUCTION: Histologic remission is associated with superior long-term clinical outcomes in ulcerative colitis (UC). VARSITY, the first head-to-head comparison of biologic agents in UC (NCT02497469; EudraCT 2015-000939-33), showed superior clinical remission and endoscopic improvement at Week 52 with vedolizumab (VDZ), a gut-selective, humanized, α4β7 integrin monoclonal antibody, vs adalimumab (ADA), a systemic, human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody. 1 Both VDZ and ADA were generally safe and well-tolerated. 1 This analysis compared histologic improvements with VDZ vs ADA in VARSITY. METHODS: Patients with moderately to severely active UC were randomized 1:1 to active VDZ intravenous (IV) infusions (300 mg)/placebo subcutaneous (SC) injections or placebo IV/active ADA SC (160/80/40 mg). Prespecified histologic exploratory endpoints included histologic remission (Geboes score < 2 or Robarts Histopathology Index [RHI] score < 3) and minimal histologic disease activity (Geboes score < 3.2 or RHI score < 5) at Week 14 and Week 52. Histologic remission was also assessed based on previous anti-TNF use. RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Median (range) duration of exposure was 477 (127, 630) days for VDZ and 420 (71, 454) days for ADA. Mean (standard deviation) baseline histologic disease activity was similar between groups (Geboes: VDZ, 15.0 [4.92]; ADA, 15.1 [5.03]; RHI: VDZ, 19.5 [8.74]; ADA, 19.6 [8.89]). Histologic remission induced by VDZ at Week 52 was greater than with ADA in the overall (Geboes or RHI), anti-TNF naïve (Geboes or RHI), and anti-TNF failure (RHI only) groups (Table 1). Histologic remission at Week 14 favored VDZ over ADA, with larger differentiation when using RHI (Table 1). VDZ also outperformed ADA in achieving minimal histologic disease activity at Weeks 14 and 52 (Table 1). CONCLUSION: VARSITY showed that use of VDZ, compared with ADA, achieved higher rates of histologic remission and minimal histologic disease activity at Weeks 14 and 52 in patients with moderately to severely active UC. These data support the use of VDZ over ADA in UC.

2590 Autoimmune Enteropathy: A Rare Cause of Chronic Diarrhea

INTRODUCTION: Autoimmune enteropathy (AIE) is a rare condition that may be easily missed without careful review of the patient's history and laboratory values. It is characterized by intractable diarrhea, malabsorption, abdominal pain, and anorexia. CASE DESCRIPTION/METHODS: A 74-year-old female with history of hypertension presented with 5 weeks of persistent nausea, vomiting, and diarrhea. These symptoms occurred while traveling. She denied consumption of unusual foods, drinking water from lakes, or fevers. Following her trip, she went to Boston. There, she had 8 non-bloody, watery bowel movements. She also noted abdominal distention and pain. She was given a 5-day course of ciprofloxacin without improvement. Once home, she presented again with weakness and dehydration. Infectious stool studies proved negative. She was treated with supportive care once again. On follow up, she was noted to have an 8-pound weight loss. She continued to have persistent diarrhea, leading to presentation to her third hospital. Repeat stool studies were positive for rotavirus. CT was consistent with enterocolitis. Labs were notable for fecal calprotectin 934, hypoalbuminemia 1.5 g/dL, and elevated CRP (44.2 mg/L). The patient underwent upper endoscopy and colonoscopy. Findings included diffuse granular mucosa with flattened villi in the gastric antrum, duodenum, and terminal ileum. Pathology revealed patchy chronic enteritis with crypt loss. The patient was started on IV solumedrol with improvement in symptoms. She was discharged on a prednisone taper for autoimmune enteritis. DISCUSSION: AIE is a rare disease among adults. AIE is diagnosed histologically by villous atrophy of the small intestine, as seen in our patient. The significance of anti-enterocyte and anti-goblet cell antibodies in AIE is unclear. A recent case series has shown no association between the clinical course and the type of gut epithelial cell antibodies. Treatment of AIE continues to evolve. Steroids are typically first used in order to control active disease. However, steroid-sparing therapies are preferred for long-term maintenance as this is a disease that typically requires ongoing immunosuppression. Use of TNF alpha-inhibitors has been trialed in a small number of patients. A recent case study studied the use of vedolizumab, an integrin-binding antibody, on a patient with good response. Overall, more cases are needed in order to improve understanding of AIE and to discover improved therapies for this rare disease.

1487 Vedolizumab-Induced Remission of Refractory Microscopic Colitis: A Single Institution Case Series

INTRODUCTION: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is responsible for up to 10-15% of chronic watery diarrhea (Cotter TG, Binder M, Loftus EV, et al. Gut 2018). While this disease is often self-limiting, some patients suffer from severe disease that can be refractory to standard medical therapies, such as Imodium and budesonide. These patients are often referred to tertiary care facilities for initiation of anti-tumor necrosis factor agents (anti-TNFs) as they have shown some benefit in refractory disease. However, a significant side effect profile does accompany these agents which can make their use less desirable. Vedolizumab, a monoclonal human antibody to α4β7-integrin that blocks lymphocyte trafficking to the gut, has an excellent safety profile (Battat R, Ma C, et al. Drug Safety 2019) and is an appealing option for patients with severe refractory MC. CASE DESCRIPTION/METHODS: Three patients presenting to the University of Kentucky with severe microscopic colitis refractory to maximum budesonide and Imodium therapy were treated with vedolizumab. Vedolizumab was given at standard induction dosing (300 mg IV at week 0, 2 and 6, and then every 8 weeks). Clinical remission was defined as <3 stools a day following induction of vedolizumab with ability to wean budesonide. DISCUSSION: All three patients had remission of their MC as evidenced by cessation of diarrhea and ability to wean budesonide and Imodium after induction vedolizumab, including one patient who had suffered from microscopic colitis for over 20 years. This case series supports the small number of case reports that have surfaced in publications over the past 18 months, the largest of which consisted of 11 patients. While the definitive mechanism of microscopic colitis remains unknown, one of the proposed mechanisms details activation of CD8 T suppressor cells in the IEC and NF-ƙβ pathway activation leading to tissue damage in epithelial cells and barrier dysfunction (Gentile N, Yen E. Gut Liver 2018). The efficacy of vedolizumab in inducing MC remission supports this proposed mechanism, given its mechanism of action to bind α4β7-integrin and prevent T-cell adhesion. Larger scale clinical trials are needed to support routine clinical use of vedolizumab in refractory microscopic colitis, but this drug presents a promising, low-side effect profile treatment option for MC suffers.

2111 Antibiotic Dependent Pouchitis Successfully Managed With Vedolizumab in a Patient With a Prior History of Renal Malignancy

INTRODUCTION: Pouchitis is a known complication of ileal pouch-anal anastomosis (IPAA). The mechanism is unknown but is felt to be due to altered bacterial flora and then a dysregulated immune response in the pouch. Although one of the mainstays of treatment is antibiotics, long-term use for patients with chronic pouchitis (CP) may not be addressing the underlying mechanism while also subjecting the patient to the risk of prolonged antibiotics. New limited data supports the use of biologics in the management of CP. We report a case of a man with a history of chronic antibiotic dependent pouchitis (CADP) and prior malignancy who was successfully managed with vedolizumab. CASE DESCRIPTION/METHODS: 44 year-old male with past medical history of ulcerative colitis status-post IPAA, renal oncytoma status-post resection (2017), non-insulin dependent diabetes, and fatty liver disease presented with persistently increased bowel movements. He endorsed weeks of twenty bowel movements per day to the point that he was awoken from sleep. He presented to urgent care where he was started on ciprofloxacin and metronidazole yet he continued to be symptomatic. He then presented to gastroenterology clinic and was started on xifaxin. He subsequently underwent a pouchoscopy showing CP (confirmed by biopsy). After some discussion, the plan was to initiate a biologic as he was refractory to antibiotics. However he was concerned about starting systemic immunosuppression given his prior malignancy. As he was post resection with reported cure and no plan to undergo further treatment, he was started on vedolizumab. On vedolizumab he endorsed resolution of symptoms with a dramatic improvement in quality of life. DISCUSSION: The challenge in management of CP arises when there is dependence on antibiotics and continued symptoms. Recent studies support the use of biologics (i.e. vedolizumab). These papers document resolution of symptoms and endoscopic improvement of disease. However there has yet to be robust data evaluating the efficacy or safety of biologics for this indication in those with prior malignancy. In this case there was initial hesitation but given the remote nature and clinical stability of the malignancy as well as gut-specificity of vedolizumab the decision was made to pursue therapy. This case highlights the successful use of vedolizumab for the treatment of CADP. The use of biologics in CP needs to further be studied, especially in a cost-benefit analysis looking further into outcomes related to long-term antibiotic use.

716 Early Clinical Response and Remission With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From VARSITY

INTRODUCTION: VARSITY is the first head-to-head trial comparing the efficacy and safety of 2 biologic therapies, vedolizumab (VDZ) and adalimumab (ADA), in patients with moderately to severely active ulcerative colitis (UC). We previously reported significantly higher rates of clinical remission (31.3% vs 22.5%; P = 0.0061) and endoscopic improvement (39.7% vs 27.7%; P = 0.0005) at Week (Wk) 52 with VDZ vs ADA. 1 METHODS: VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-controlled study (NCT02497469; EudraCT 2015-000939-33). Here we report the predefined, exploratory endpoints of early clinical response and clinical remission (defined in the Table 1) within the first 14 wks, as well as durable clinical remission (patients in clinical remission at Wk 14 and Wk 52). RESULTS: A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Baseline characteristics were comparable between the 2 groups. A trend for separation in clinical response started to emerge at Wk 6 favoring VDZ vs ADA. Clinical response at Wk 14 favored VDZ vs ADA (257 [67.1%] vs 177 [45.9%]; treatment difference 21.2%). More patients achieved clinical remission at Wk 14 on VDZ vs ADA (102 [26.6%] vs 82 [21.2%]; treatment difference 5.3%). Patients on VDZ achieved higher rates of durable clinical remission (70 [18.3%] vs 46 [11.9%]); laboratory results correlated with these findings. Post hoc analyses showed a larger mean (standard deviation) change of C-reactive protein (CRP) from baseline to Wk 14 (−32.88 [155.77] nmol/L VDZ vs −3.35 [260.81] nmol/L ADA) and to Wk 52 (−50.87 [174.76] nmol/L VDZ vs −37.21 [169.17] nmol/L ADA) in favor of VDZ. Greater mean declines in fecal calprotectin (FCP) levels were seen in patients on VDZ compared with ADA (Wk 14: −1,551.3 [6,236.70] mg/kg VDZ vs −1,167.6 [4,647.67] mg/kg ADA; Wk 52: −2,187.3 [7,440.42] mg/kg VDZ vs −1,846.6 [4,560.55] mg/kg ADA). CONCLUSION: Patients on VDZ had numerically higher rates of both clinical response and clinical remission by Wk 14 compared with ADA. Patients on VDZ also achieved higher rates of durable clinical remission compared with ADA. CRP and FCP results correlated with these findings. These data on early clinical response and clinical remission, as well as durable remission, further support the use of VDZ over ADA in patients with moderately to severely active UC.

2059 A Case of Hepatosplenic T-cell Lymphoma in a Patient on Vedolizumab for Crohn’s Disease

INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL) is a rare malignancy, most commonly affecting young males with often fatal prognosis. In patients with inflammatory bowel disease (IBD), HSTCL has been associated with thiopurine analog and tumor necrosis factor (TNF)-α inhibitor therapy; particularly when used in combination, the risk increases up to 4 fold. Development of HSTCL has not been reported in association with vedolizumab. CASE DESCRIPTION/METHODS: A 22-year-old male with severe, stricturing colonic Crohn’s disease of 10 years duration, on vedolizumab monotherapy every 4 weeks for 15 months, was incidentally noted to be pancytopenic in October 2016 and subsequently diagnosed with HSTCL by bone marrow biopsy. Previous IBD therapies included mesalamine, azathioprine, infliximab, adalimumab, intravenous immunoglobulin (IVIG), budesonide, certolizumab pegol and most recently 6 mercaptopurine (6-MP). The 6-MP was discontinued 1 year prior to HSTCL diagnosis. He achieved remission with chemotherapy, followed by autologous stem-cell transplant in September 2017. Unfortunately his disease relapsed only a few months later. He achieved a second remission with salvage chemotherapy, and proceeded to allogeneic bone marrow transplant in April 2018. Since diagnosis of HSTCL, he did not receive any therapy for Crohn’s disease and has been asymptomatic from his IBD. Colonoscopy demonstrated complete endoscopic and histologic remission as well. On last bone marrow biopsy, over 200 days post-transplant, there was no evidence of HSTCL relapse 24 months following HSTCL diagnosis. DISCUSSION: Fortunately, our case had a favorable outcome compared to those reported in the literature with a median overall survival of 10 months, and up to 17 months in patients who receive stem cell transplant. In addition, following stem cell transplant, our patient achieved cure of his Crohn’s disease. A recent review of patients with immunoregulatory disorders who developed HSTCL noted that 56% of patients were treated with TNF-α inhibitors versus 89% with immunomodulators, indicating that the latter pose higher risk. To our knowledge, there have not been reports of HSTCL associated with vedolizumab use nor is there a known mechanism by which vedolizumab could cause HSTCL. In our case, TNF-α inhibitor was stopped 5 years prior and thiopurine analog 1 year prior to diagnosis, raising the question as to how long the risk of HSTCL remains elevated after cessation of such agents.

839 Response and Healthcare Resource Utilization in Inflammatory Bowel Disease Patients Treated With Either Infliximab or Vedolizumab

INTRODUCTION: Both infliximab (IFX) and vedolizumab (VDZ) are FDA-approved for treatment of inflammatory bowel disease (IBD) in adults. Much of the published data on clinical outcomes for either IFX or VDZ compare the biologic agent against more traditional therapies rather than alternative biologics. The aim of this study was to evaluate clinical response and healthcare resource utilization (HRU) in IBD patients (pts) treated with either IFX or VDZ for 12 months (mos). METHODS: We performed a review of adult Crohn’s disease (CD) and ulcerative colitis (UC) pts who initiated treatment with either IFX or VDZ from 2016-2018 at a large multicenter, gastroenterology private practice. Those who persisted on therapy for 12 mos were identified. Pts were case-matched 1:1 based on age, gender, diagnosis, and baseline disease severity scores using the partial Mayo (pMayo) for UC and the modified Harvey-Bradshaw Index (mHBI) for CD. Primary endpoints were changes in disease activity at 3, 6, and 12 mos compared to baseline, and IBD-related HRU, defined as emergency department (ED) visits, and hospitalizations during the 12 mos. Additionally, adverse drug reactions (ADR) and infections were assessed. RESULTS: Case-matching yielded 35 IFX (16 CD, 19 UC) and 35 VDZ (16 CD, 19 UC) pts for further assessment. Demographics were similar between groups: mean age 38 ± 20 vs 40 ± 15, male gender 54% vs 51%. Baseline scores were similar as noted in Figure 1. In the overall assessment of response between groups, both IFX and VDZ in CD were associated with a reduction in HBI score of >60% at 3 mos. IFX and VDZ use in UC were associated with reductions in pMayo scores at 3 mos of 56% and 44%, respectively. These substantial reductions were sustained through 12 mos. IFX-treated pts had 4 IBD-related ED visits with 1 hospitalization, while VDZ-treated pts had 5 IBD-related ED visits and 4 hospitalizations. Infection rates were similar with 8 infections in IFX pts (23%) and 7 in VDZ pts (20%); 1 VDZ infection led to hospital admission. Thirteen (5 IFX, 8 VDZ) non-serious infusion-related ADRs were reported with no difference between treatment groups. CONCLUSION: The data demonstrate similarity in response and healthcare resource utilization over time with use of IFX or VDZ in the treatment of IBD patients. Although the number of case-matched patients in this study is limited and the population is restricted to responders, resource utilization was noticeably low. Additional study is warranted.

736 Vedolizumab: Peri-Operative Infection Rates in Patients With IBD

INTRODUCTION: Vedolizumab (VDZ), a humanized monoclonal antibody, binds to the alpha4beta7 integrin and blocks the interaction of mucosal cell adhesion molecule-1 thus inhibiting the migration of memory T-lymphocytes into inflamed GI parenchymal tissue. This interaction is a hallmark of Ulcerative colitis (UC) and Crohn's disease (CD). It has been used as an alternative therapy to anti-tumor necrosis factor (anti-TNF) agents for Induction and maintenance in patients with moderate to severe inflammatory bowel diseases (IBD). Due to its immunosuppressive effects, VDZ maybe associated with increased risks of infections. Therefore, it is imperative to study the infection rate in this population, particularly during the perioperative period. Our objective is to identify perioperative infection rates in patients with Inflammatory Bowel Disease (IBD). METHODS: A retrospective multi-center case-control study was conducted. Patients with IBD in the period from May 2014 to Dec 2017 were included. Two groups were studied (Pt with IBD and on VDZ, Pt with IBD and not on VDZ). The perioperative period was identified as up to 30 days post-index surgery. ICD-10 codes for intra-abdominal surgeries and infections were used to identify population. Patients developing only new infections were included. Data were classified into two cohorts for the purpose of comparison: Cohort 1 included all-infections and Cohort 2 included only intra-abdominal infection. Different models of logistic regression data analysis were performed. RESULTS: Logistic regression data analysis was performed including simple, multiple and mixed model for both cohorts. The mixed model included multiple encounters per person, age, gender, ethnicity, and race. Results of Cohort 1 showed odds ratio (OR) = 1.332 (CI 0.599-2.965, P = 0.4821). Results of Cohort 2: OR = 1.286 (CI 0.426-3.882, P = 0.6551). These findings indicated that there was no statistical significance between increased rates of peri-operative infection rates and VDZ use. CONCLUSION: Our findings suggested that VDZ is relatively safe to use during the perioperative period. There are a few small studies indicating similar results, however, a unique aspect of our study was to include broad-spectrum infection types (sepsis from any source such as pneumonia, UTI) and not only intra-abdominal or surgery-related infections. We do recommend further investigations with more controlled study and larger population coverage to further solidify our findings.

647 Risk of New or Recurrent Cancer in Patients With Inflammatory Bowel Disease and Previous Cancer Exposed to Vedolizumab or Ustekinumab

INTRODUCTION: Previous studies have demonstrated that exposure to anti-TNFα and/or immunomodulators for inflammatory bowel disease (IBD) following a diagnosis of cancer was not associated with an increased risk of new or recurrent cancer. There is little data regarding the use of newer biologics, vedolizumab and ustekinumab, after a diagnosis of cancer. We aimed to investigate whether patients with IBD and a history of cancer who were subsequently exposed to vedolizumab or ustekinumab have an increased risk of developing new or recurrent cancer. METHODS: We reviewed the medical records of 5062 patients with IBD and cancer from an academic medical center between January 2013 and November 2018 to identify IBD patients who received vedolizumab or ustekinumab following a diagnosis of cancer. We collected demographic, IBD and cancer-related data. Our primary outcome was the development of new or recurrent cancer. Results were compared to historical data regarding the risk of new or recurrent cancer in patients exposed to anti-TNFα, an immunomodulator or no therapy for IBD following a diagnosis of cancer. RESULTS: We identified IBD patients who received vedolizumab (n = 59) or ustekinumab (n = 18) monotherapy following a diagnosis of cancer (Table 1). The median age at cancer diagnosis was 51 years (IQR 43-65) for vedolizumab and 57 years (IQR 55-66) for ustekinumab. During a median follow-up of 68 months (IQR 21-132) for vedolizumab and 48 months (IQR 12-96) for ustekinumab, 3 (5%) and 3 (17%) patients developed subsequent cancer, respectively. Compared to historical data, there were differences in subsequent cancer risk between exposure groups (Figure 1; log-rank 0.001). However, when adjusted for stage of prior cancer, compared to no therapy, there was no difference in risk of new or recurrent cancer between patients exposed to vedolizumab (HR 0.01, 0.01-7.58), ustekinumab (HR 0.85, 0.11-6.50), anti-TNFα (HR 0.60, 0.34-1.07) or immunomodulators (HR 1.01, 0.58-1.75) following a diagnosis of cancer. CONCLUSION: In this single-center study, exposure to vedolizumab or ustekinumab in patients with IBD and a history of cancer conferred a low risk of new or recurrent cancer. Exposure to vedolizumab or ustekinumab monotherapy was not associated with an increased risk of subsequent cancer compared to historical data of exposure to anti-TNF, immunomodulators or no immunosuppression following a diagnosis of cancer. Larger studies are needed to confirm these findings.

638 Clinical Effectiveness of First-Line Anti-TNF Therapies and Second-Line Anti-TNF Therapy Post-Vedolizumab Discontinuation in Patients With Ulcerative Colitis or Crohn's Disease

INTRODUCTION: Real-world data is needed to understand and compare the clinical effectiveness of second-line (2L) anti-tumour necrosis factors (anti-TNF) treatment (Tx) post first-line (1L; biologic-naive) vedolizumab (VDZ) and 1L anti-TNF use in patients (pts) with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: This was a real-world, multi-country, multi-centre retrospective study in UC and CD pts (≥18 years old) treated with 1L anti-TNF or 2L anti-TNF after discontinuation of 1L VDZ for any reason (received May 2014-March 2018). Pts were from sites in Canada, Greece and the United States. Anti-TNF therapies included adalimumab, infliximab, golimumab and certolizumab pegol. The index date was defined as date of 1L Tx initiation. Clinical effectiveness data were collected from 1L or 2L Tx initiation to earliest of death, chart abstraction date. Cumulative rates of Tx persistence, clinical response and clinical remission were estimated using the Kaplan-Meier method for UC and CD (separately and combined) over 6 months. Clinical response and remission were assessed using pre-defined hierarchical algorithms of standard disease measures reported in the medical records. P-values were generated using the log-rank test. RESULTS: This analysis included 579 anti-TNF patients (1L: 497 [UC: 224; CD: 273]; 2L: 82 [UC: 58; CD: 24]) from 36 sites. Proportions of patients in each cohort were: adalimumab (1L: 41.4%; 2L: 19.5%), infliximab (1L: 52.7%; 2L: 79.3%), golimumab (1L: 4.8%; 2L: 1.2%) and certolizumab pegol (1L: 0.8%; 2L: 0.0%). Mean (SD) age at index date: 1L, 39.6 (15.2); 2L, 49.4 (18.6) years, male: 1L, 49.9%; 2L, 61.0%, median (range: min-max) disease duration: 1L, 2.0 (<0.1–49.0); 2L, 3.7 (0.1–54.0) years. At 6 months, cumulative rates of Tx persistence (1L: 83.9%; 2L: 83.6%), clinical response (1L: 49.5%; 2L: 65.6%) and clinical remission (1L: 29.5%; 2L: 31.4%), were similar between 1L and 2L patients (Table 1). Results were similar when data were stratified by UC and CD (Table 1), albeit sample sizes were small. CONCLUSION: Cumulative rates of Tx persistence, clinical response and clinical remission were comparable between 1L anti-TNF patients and those who switched to a 2L anti-TNF following the discontinuation of 1L VDZ. Results suggest that 1L VDZ may not impact the effectiveness of subsequent anti-TNF Tx in real-world clinical practice. As 2L sample size was limited, these hypothesis-generating data warrant further study.

Vedolizumab use in patients with inflammatory bowel diseases undergoing surgery: clinical trials and post-marketing experience.

BackgroundPatients 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.MethodsThis 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.ResultsOf 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-term safety 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.ConclusionsIn 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.

300.7: Isolated intestinal transplantation: Are we shifting the paradigm?

Introduction: Isolated intestinal transplant (IIT) is the definitive therapy for intestinal failure. Outcomes have improved tremendously in the last decade. Our center has performed almost 500 intestinal inclusive transplants. Intestine-Colon may be the best nomenclature for better defining the current procedure. Method: We describe all the patients who received IIT from 2013 to 2018 in our center. It represents our most recent Era with the evolution of surgical technique, immunosuppression regimen, graft monitoring and patient management. Immunosuppression consisted of induction with thymoglobulin and rituximab, maintenance with tacrolimus and mTOR inhibitor and use of basiliximab or vedolizumab for the first 3 months. Results: 31 IIT were performed in 30 patients at our center. 13 were male. 11 of the recipients were pediatric. Recipient age went from 1 year old to 65 years old. Main indication for transplant was short gut. Positive crossmatch was found in 14% of the transplants. Moderate or severe rejection has happened in 32% of the patients. Only 1 patient underwent to enterectomy within 90 days due to rejection. One patient lost the graft due to volvulus. One patient had the graft removed during emergent surgery due to rupture of mycotic aneurism. Two patients developed PTLD. GVHD was not seen in this cohort. Chronic rejection or chronic graft dysfunction was not observed. Kaplan Meyer 5 year patient and graft survival for primary, non-renal transplants, was 92% and 77% respectively. 5 year patient survival including re-transplants and intestine-kidneys transplants is 87%. Patient survival 1 year remains 100% for all the patients. Discussion: Survival of intestine-colon transplant has greatly improved over time. Historically, rejection was the main reason for graft and patient loss. In this cohort, only half of the graft losses were due to rejection. Mortality or graft loss due to causes unrelated directly to transplant was the majority in our experience. New immunosuppressive strategies have shown excellent results preventing rejection. Chronic rejection is a well-known long term complication for IIT, although no cases were seen up to date. 100% patient survival for the first year and 92% patient survival for 5 years surpasses all the data available not only for intestines but for all other organs. We believe we are entering a new era in intestinal transplant, with extremely high patient survival even when compared with other modalities of treatment for intestinal failure.

Changes in Patient-Reported Outcomes With Vedolizumab Therapy in Patients With Inflammatory Bowel Diseases (IBD): Results From the IBD Partners Patient Powered Research Network

Abstract Background We described changes in patient-reported outcomes (PROs) with vedolizumab (VDZ) use in inflammatory bowel disease (IBD). Methods We included patients initiating VDZ with at least 6 months of follow-up in the IBD Partners cohort. We stratified by biologic naive (BN) or biologic exposed (BE) status. Outcomes included PROs. Results We included 380 patients with IBD. Remission rates at follow-up were higher for BN versus BE (65.1% vs 45.5%, P < 0.01). BN patients experienced significant improvements in social satisfaction (P < 0.01). BN status was associated with remission (adjusted odds ratio, 3.36; 95% confidence interval, 1.67–6.77). Conclusions Improvements in PROs were seen with VDZ, particularly in BN populations.

Su1835 – Vedolizumab Use is Not Associated with Increased Malignancy Incidence: Gemini Long-Term Safety Study Results and Post-Marketing Data

Su1835 – Vedolizumab Use is Not Associated with Increased Malignancy Incidence: Gemini Long-Term Safety Study Results and Post-Marketing Data

P724 Vedolizumab use is not associated with increased malignancy incidence: GEMINI LTS study results and post-marketing data

Background Vedolizumab is a gut-selective antibody to α4 β7 integrin approved to treat moderate-to-severe Crohn's disease and ulcerative colitis in adults. Inflammatory bowel disease (IBD) and immunosuppressant use are associated with increased risk of malignancy. Aim To analyse the incidence of malignancy with vedolizumab treatment in the GEMINI long-term safety (LTS) study and post-marketing (PM) setting. Methods Malignancy data from the LTS study (May 2009 to May 2018), and data from the vedolizumab Global Safety Database (20 May 2014 to 19 May 2018), were identified using Medical Dictionary for Regulatory Activities coding. The number of patients experiencing malignancies in the LTS study (excluding malignancies within 1 year following vedolizumab initiation) was indirectly standardised against the number expected, using age- and sex-specific rates in patients with IBD from Optum's Clinformatics™ Data Mart (CDM) database. Results Among 1785 patients with ≥1 year of follow-up post-vedolizumab initiation in the LTS study (total 5670 patient-years), observed numbers of malignancies were similar to those expected compared with CDM data (31 vs 29; ratio of observed to expected events = 1.08; P = 0.71; 95% confidence intervals [CI] 0.73, 1.53). The most common malignancies were renal and bladder (6). PM, 293 patients reported 299 malignancies (including malignancies within 1 year following vedolizumab initiation), in approximately 208 050 patient-years of vedolizumab exposure. Lower gastrointestinal malignancies were most common (59). Conclusions The number of malignancies in the LTS study was similar to that expected from an IBD population with no statistically significant differences, although few confounders could be corrected for. Limitations of PM safety reporting require consideration; however, the number of malignancies with vedolizumab appeared low.

P183 Colombian real-world experience of vedolizumab use in patients with inflammatory bowel disease—EXVEDOCOL

P183 Colombian real-world experience of vedolizumab use in patients with inflammatory bowel disease—EXVEDOCOL

Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient?

Çekiç Ş, Özgür T, Karalı Y, Özkan T, Kılıç SŞ. Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient? Turk J Pediatr 2019; 61: 937-940. The loss of inflammatory regulation resulting from the absence of B-lymphocytes leads to a risk for autoimmune and autoinflammatory complications. There is no data on the use of Vedolizumab in patients with X-linked agammaglobulinemia (XLA) as well as children with another primary immunodeficiency (PID) diseases. A 4-year-old boy was admitted to our clinic with a history of recurrent respiratory tract infections. He was diagnosed with XLA based on extremely low immunoglobulins, very low level of B cells, genetic mutation of BTK gene, and family history. At the age of 8, he suffered from intermittent fever attacks, abdominal pain, weakness, oral aft, and weight loss. His clinical and laboratory features were consistent with inflammatory bowel disease. Histopathological examination of the biopsy material obtained from terminal ileum, colon and cecum showed Crohn`s disease. Initially, he was treated with prednisolone and infliximab. Because of the lack of response, infliximab treatment was switched to adalimumab. Terminal ileum was resected to relieve obstruction complication. Although he had been treated with adalimumab, a significant improvement was not observed. Vedolizumab (Entyvio™), a humanized monoclonal antibody α4β7 integrin-receptor antagonist, was commenced. After treatment with vedolizumab, his fever and abdominal pain attacks reduced, his total daily calorie intake increased and weight gain improved. He began to walk again and continued his school education properly. No side effects were observed in 18 months. This is the first immunocompromised child treated with vedolizumab. The symptoms of the patient receded and no side effect were seen during the treatment.

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.

Vedolizumab in the treatment of inflammatory bowel diseases: whom and how?

The article is devoted to the use of vedolizumab, an α4β7 integrin antagonist, in the treatment of inflammatory bowel diseases (ulcerative colitis and Crohn’s disease). It presents the results of clinical trials of the drug and the experience of using vedolizumab in actual clinical practice. The latest available information about the drug’s safety profile is provided. The authors considered the practical aspects of therapy, such as determining the indications for treatment, tactics in loss of response, the need for a combination of vedolizumab with immunosuppressors, and the use of the drug in specific categories of patients.

What Is the Most Cost-Effective Position of Vedolizumab in Treatment Algorithms of Ulcerative Colitis From a Population Management Perspective?

Introduction: Prior cost-effectiveness analyses assessing vedolizumab (VDZ) use in Ulcerative colitis (UC) have compared VDZ head to head with other biologic agents. In the real world, the mixed usage patterns of the more commonly used anti-TNFs, infliximab (IFX) and adalimumab (ADA), vary. We aimed to assess the ideal position for VDZ in UC treatment algorithms when accounting for the use of either IFX or ADA as the existing first line anti-TNF from a population management perspective. Methods: We employed aMarkov model to identify the most cost-effective position for VDZ in 3 different positions in a step-up treatment algorithm for UC (Figure 1): (A1) prior to initiating either combined IFX + azathioprine (AZA) or ADA+AZA, (A2) prior to combination therapy with a second anti-TNF, and (A3) last-line prior to colectomy. With each therapy, individuals could enter clinical remission or response, or develop a complication including infection, lymphoma, or other adverse events. Transition probabilities were derived from published clinical trials including ACT, GEMINI, SUCCESS, and ULTRA-2, stratified by prior exposures. Utilities and costs were derived from published estimates, Medicare reimbursement rates, the Nationwide Inpatient Sample, and wholesale acquisition costs. Primary analyses consisted of probabilistic simulations of 100,000 individuals at 1 year. Three separate analyses were conducted, with 50% IFX+AZA and 50% ADA+AZA use, 100% IFX+AZA use, and 100% ADA+AZA use. Threshold analyses was performed varying the existing treatment mix percentage between ADA and IFX to determine if this influenced the preferred strategy. All models assumed a willingness-to-pay (WTP) threshold of $100,000 per quality adjusted life year gained.636_A Figure 1. Overview of base model structureResults: In this model, the preferred strategy was VDZ used as first line biologic before an initial trial of combination therapy (A1) when ADA was used as the first anti-TNF for 50% or 100% of individuals, or VDZ use before cycling to a second anti-TNF if 100% of individuals used IFX as their first anti-TNF (Table 1). In threshold analysis, VDZ use was preferred prior to an anti-TNF for a UC population if >9% of individuals started with ADA. Conclusion: This model suggests that in moderate to severe UC, utilizing VDZ as the first biologic (prior to IFX+AZA or ADA+AZA) may be the most cost-effective strategy for payers in markets, particularly if >9% of individuals select ADA instead of infliximab as their first anti-TNF.636_B Figure 2. Results of cost-effectiveness analysis for each strategy and overall ICERs at 1, 3, 5, and 7 years for the base model and key structural sensitivity analyses. Results for strongly dominated strategies and negative ICER calculations are not reported. Reported ICERs are calculated from non-dominated strategies in order of increasing effectiveness. Abbreviations: ICER: Incremental cost-effectiveness ratio, QALY: Quality-adjusted life year, VDZ: Vedolizumab, ADA: Adalimumab, IFX: Infliximab, AZA: Azathioprine636_C Figure 3 No Caption available.