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William J. Sandborn - One of the best experts on this subject based on the ideXlab platform.
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Long-term safety of Vedolizumab for inflammatory bowel disease.
Alimentary pharmacology & therapeutics, 2020Co-Authors: Edward V. Loftus, William J. Sandborn, Silvio Danese, Brian G Feagan, Jeanfrederic Colombel, Remo Panaccione, Bruce E. Sands, Geert R. D'haens, David T. Rubin, Ira ShafranAbstract:Background Vedolizumab, a gut-selective α4 β7 integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). Aim To report the final results from the Vedolizumab GEMINI long-term safety (LTS) study. Methods The phase 3, open-label GEMINI LTS study (initiated May 2009) enrolled patients with UC or CD from four prior clinical trials and Vedolizumab-naive patients. Vedolizumab LTS was evaluated; efficacy and patient-reported outcomes were exploratory endpoints. Results Enrolled patients (UC, n = 894; CD, n = 1349) received Vedolizumab 300 mg IV every 4 weeks; median cumulative exposure was 42.4 months (range: 0.03-112.2) for UC and 31.5 months (range: 0.03-100.3) for CD. Over 8 years, adverse events (AEs) occurred in 93% (UC) and 96% (CD) of patients, with UC (36%) and CD (35%) exacerbations most frequent. Serious AEs were reported for 31% (UC) and 41% (CD) of patients. Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients. There were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy. Of the ten deaths (UC, n = 4; CD, n = 6), two were considered drug-related by local investigators (West Nile virus infection-related encephalitis and hepatocellular carcinoma). Continuous Vedolizumab maintained clinical response long-term, with 33% (UC) and 28% (CD) of patients in clinical remission at 400 treatment weeks. Conclusions The safety profile of Vedolizumab remains favourable with no unexpected or new safety concerns. These results further establish the safety of Vedolizumab and support its long-term use (NCT00790933/EudraCT 2008-002784-14).
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systematic review with meta analysis association between Vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases
Alimentary Pharmacology & Therapeutics, 2019Co-Authors: Siddharth Singh, Parambir S Dulai, Niels Vande Casteele, Robert Battat, Mathurin Fumery, Brigid S Boland, William J. SandbornAbstract:Background There has been limited evaluation of the association between Vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD). Aim To perform a systematic review and meta-analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for Vedolizumab. Methods Through a systematic literature search through 28 February 2019, we identified five cohort studies (558 patients, 42% with ulcerative colitis) reporting the association between Vedolizumab trough concentration and clinical outcomes in patients with IBD. We calculated mean difference (MD) in Vedolizumab trough concentration in patients achieving vs not achieving clinical outcomes, and qualitatively synthesized thresholds associated with favourable outcomes. Results In patients with UC, median Vedolizumab trough concentrations were consistently higher in patients achieving clinical remission (median, 14.3 μg/mL vs 10.5 μg/mL; MD, 5.1 μg/mL, 95% CI, 2.8-7.4) or endoscopic remission (median, 13.0 μg/mL vs 9.7; MD, 5.1 μg/mL, 95% CI, 2.2-7.9). In patients with CD, there was no significant difference in median Vedolizumab trough concentrations in patients achieving vs not achieving clinical remission (MD, 2.0 μg/mL; 95% CI, -0.5 to 4.5) or endoscopic remission (MD, 3.6 μg/mL; 95% CI, -1.4 to 8.6). In patients with UC, week 6 Vedolizumab trough concentrations ≥18.5-20.8 μg/mL, and maintenance trough concentrations ≥9.0-12.6 μg/mL were associated with favourable clinical outcomes. Antibodies to Vedolizumab were reported in 1.7%-3.0% patients on maintenance therapy. Conclusion Based on meta-analysis, patients with UC who achieve endoscopic and clinical remission have significantly higher Vedolizumab trough concentration during maintenance therapy. Vedolizumab trough concentration >20 μg/mL at week 6, and >12 μg/mL during maintenance may be associated with better outcomes, though cause-effect relationship remains unclear. Prospective studies on reactive and proactive therapeutic drug monitoring of Vedolizumab (vs empiric dose escalation) are warranted.
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Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis.
Gastroenterology, 2019Co-Authors: William J. Sandborn, María Rosario, Jingjing Chen, Filip Baert, Silvio Danese, Ž. Krznarić, Taku Kobayashi, X Yao, Siddharth Bhatia, K KisfalviAbstract:Background & Aims Maintenance treatment with Vedolizumab, a monoclonal antibody that inhibits the gut-selective α4β7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of Vedolizumab for maintenance treatment. Subcutaneous Vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis. Methods We performed a phase 3, double-blind, double-dummy trial at 141 sites in 29 countries from December 18, 2015 through August 21, 2018. Patients with moderately to severely active ulcerative colitis received open-label treatment with intravenous Vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous Vedolizumab 108 mg every 2 weeks, intravenous Vedolizumab 300 mg every 8 weeks, or placebo. The primary end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1. Results Among the randomized 216 patients, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous Vedolizumab, intravenous Vedolizumab, and placebo groups, respectively (subcutaneous Vedolizumab vs placebo: Δ32.3%; 95% confidence interval, 19.7%–45.0%; P Conclusions Subcutaneous Vedolizumab is effective as maintenance therapy in patients with moderately to severely active ulcerative colitis who had a clinical response to intravenous Vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.
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oth 12 efficacy and safety of Vedolizumab subcutaneous formulation for ulcerative colitis results of the visible trial
Gut, 2019Co-Authors: William J. Sandborn, Filip Baert, Silvio Danese, Taku Kobayashi, X Yao, K Kisfalvi, Krznari Z Cacute, G Dhaens, J Chen, Severine VermeireAbstract:Introduction Vedolizumab, a gut-selective, humanised, monoclonal α4b7 integrin antibody, is available as an intravenous (IV) formulation to adult patients (pts) with moderately to severely active ulcerative colitis (UC) or Crohn’s disease. We present the phase 3 results on a new subcutaneous (SC) formulation for maintenance treatment in UC. Methods A randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial (NCT02611830) assessed Vedolizumab SC as maintenance treatment in adult pts with active UC. An open-label induction with Vedolizumab IV (300 mg) was administered at Weeks (Wks) 0 and 2, with disease evaluation at Wk 6. Pts with a clinical response at Wk 6 (complete Mayo score reduction of ≥3 points and ≥30% from baseline [Wk 0] plus reduction in rectal bleeding subscore of ≥1 point or absolute subscore of ≤1 point) were randomised (2:1:1) to receive Vedolizumab SC (108 mg every 2 wks), or Vedolizumab IV (300 mg every 8 wks) or placebo for up to 52 wks. The primary objective was to assess clinical remission (defined as complete Mayo score of ≤2 points and no individual subscore >1 point) with Vedolizumab SC vs placebo at Wk 52. Between-group treatment effects were compared using the Cochran-Mantel-Haenszel test with stratification by study randomisation factors (concomitant corticosteroid use, Wk 6 remission status, and prior anti-TNFα failure or immunomodulator use). Results A total of 383 pts received open-label Vedolizumab IV induction. Of those, 216 (56.4%) experienced clinical response at Wk 6 and entered the maintenance phase. At Wk 52, 46.2% of pts on Vedolizumab SC vs 14.3% on placebo were in clinical remission (p Conclusions Vedolizumab SC 108 mg every 2 wks was efficacious, generally safe and well-tolerated as maintenance therapy in UC pts following induction with Vedolizumab IV 300 mg showing an efficacy and safety profile similar to that of the currently available IV formulation.
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deep remission with Vedolizumab in patients with moderately to severely active ulcerative colitis a gemini 1 post hoc analysis
Journal of Crohns & Colitis, 2019Co-Authors: María Rosario, William J. Sandborn, Morris Barocas, Parambir S Dulai, Jeanfrederic Colombel, Remo Panaccione, Charlie Cao, Karen LaschAbstract:Background and Aims This GEMINI 1 post hoc analysis evaluated Vedolizumab efficacy for inducing deep remission in patients with ulcerative colitis and correlation between Vedolizumab trough concentrations and deep remission rates. Methods Week 6 Vedolizumab responders were re-randomized to placebo or Vedolizumab every 8 or 4 weeks. Deep remission at Week 52 was measured using four different definitions [from most to least stringent]: [1] Mayo Clinic endoscopic score = 0, rectal bleeding score = 0 and decrease or no change from baseline in stool frequency score; [2] endoscopic score ≤1, rectal bleeding score = 0 and stool frequency score = 0; [3] endoscopic score ≤1, rectal bleeding score = 0, decrease or no change from baseline stool frequency score, and total score [endoscopic score + rectal bleeding score + stool frequency score] ≤1; and [4] endoscopic score ≤1, rectal bleeding score = 0 and stool frequency score ≤1. Steady-state trough Vedolizumab serum concentrations were evaluated. Results At Week 6, 373 Vedolizumab responders were re-randomized to maintenance placebo [n = 126] or Vedolizumab every 8 [n = 122] or 4 [n = 125] weeks. Significantly more Vedolizumab patients achieved deep remission at Week 52 for the most (placebo 8.7%, every 8 weeks 27.0% [p = 0.0001], every 4 weeks 28.0% [p < 0.0001]) and least (placebo 15.9%, every 8 weeks 43.4% [p < 0.0001], every 4 weeks 43.2% [p < 0.0001]) stringent definitions. Patients with higher Vedolizumab trough concentration quartiles had higher deep remission rates [all definitions] compared with those with the lowest quartile or who received placebo. Conclusion Vedolizumab was associated with significantly higher deep remission rates than placebo at Week 52, regardless of deep remission definition [NCT00783718].
Amy L. Lightner - One of the best experts on this subject based on the ideXlab platform.
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Vedolizumab in the Perioperative Management of Inflammatory Bowel Disease.
Current drug targets, 2019Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Edward V. Loftus, Laura E. RaffalsAbstract:BACKGROUND The isolated effect of Vedolizumab on increased postoperative complications remains debated, similar to the controversial data on anti-TNF and postoperative complications. OBJECTIVE To determine the risk of Vedolizumab on postoperative complications. METHODS A review of the literature available to date on studies comparing postoperative outcomes in Vedolizumab-treated versus non-Vedolizumab-treated patients was performed. Studies were stratified by those which combined all inflammatory bowel disease together, those specifically focusing on Crohn's disease or ulcerative colitis individually, and those which included pediatric patients alone. RESULTS The data remains controversial in both the adult and pediatric literature regarding the association of Vedolizumab and increased postoperative complications. The strongest association between Vedolizumab and an increased risk of postoperative infectious complications seems to be in the Crohn's disease literature. CONCLUSION Vedolizumab may be associated with an increased risk of postoperative infectious complications in Crohn's disease, but the literature remains controversial due to difficulty in isolating the effect of the biologic alone in a chronically ill, heterogeneous patient population who are on multiple medications including corticosteroids.
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postoperative outcomes in Vedolizumab treated patients undergoing major abdominal operations for inflammatory bowel disease retrospective multicenter cohort study
Inflammatory Bowel Diseases, 2018Co-Authors: Amy L. Lightner, Bo Shen, Parambir S Dulai, John H. Pemberton, Kellie L. Mathis, Gursimran Kochhar, Chung Sang Tse, Amandeep Singh, Samuel Eisenstein, William J. SandbornAbstract:Background Vedolizumab is now widely available for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). We sought to quantify the rates of postoperative complications with preoperative Vedolizumab compared with anti-tumor necrosis factor (anti-TNF) therapy. Methods A multicenter retrospective review of adult inflammatory bowel disease (IBD) patients who underwent an abdominal operation between May 20, 2014, and December 31, 2015, was performed. The study cohort was comprised of patients who had received Vedolizumab within 12 weeks of their abdominal operation, and the control cohort was IBD patients who had received anti-TNF therapy. Results A total of 146 patients received Vedolizumab within 12 weeks before an abdominal operation (64% female; n = 93; median age, 33 years; range, 15-74 years), and 289 patients received anti-TNF therapy (49% female; n = 142; median age, 36 years; range, 17-73 years). Vedolizumab-treated patients were younger (P = 0.015) and were more likely to have taken corticosteroids (P < 0.01) within the 12 weeks before surgery. Vedolizumab-treated patients had a significantly increased risk of any postoperative surgical site infection (SSI; P < 0.01), superficial SSI (P < 0.01), deep space SSI (P = 0.39), and mucocutaneous separation of the diverting stoma (P < 0.00) as compared with patients taking anti-TNF therapy. On multivariate analysis, after adjusting for body mass index, steroids at the time of operation, and institution, exposure to Vedolizumab remained a significant predictor of postoperative SSI (P < 0.01). Conclusions We observed that Vedolizumab-treated patients were at significantly increased risk of postoperative SSIs after a major abdominal operation, as compared with anti-TNF-treated patients.
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postoperative outcomes in Vedolizumab treated crohn s disease patients undergoing major abdominal operations
Alimentary Pharmacology & Therapeutics, 2018Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS Twenty-six per cent of Crohn's disease patients who received Vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While Vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.
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Postoperative outcomes in Vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.
Alimentary pharmacology & therapeutics, 2017Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P
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postoperative outcomes in Vedolizumab treated patients undergoing abdominal operations for inflammatory bowel disease
Journal of Crohns & Colitis, 2017Co-Authors: Amy L. Lightner, John H. Pemberton, Laura E. Raffals, Kellie L. Mathis, Chung Sang Tse, Robert R Cima, Eric J Dozois, Edward V. LoftusAbstract:Introduction: Vedolizumab was recently FDA approved for treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). No study to date has examined the rate of postoperative infectious complications among patients who received Vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among IBD patients who received Vedolizumab within 12 weeks of an abdominal operation as compared to patients who received TNFα inhibitors or no biologic therapy. Methods: A retrospective chart review between 5/1/2014 and 12/31/2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort was comprised of patients who received Vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNFα inhibitors or no biologic therapy. Results: 94 patients received Vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications (53%), 35 of which were surgical site infections (SSIs) (36%). The Vedolizumab group experienced significantly higher rates of any postoperative infection (53% vs 33% anti-TNF and 28% non-biologic; P<0.001) and SSI (37% vs 10% and 13%; P< 0.001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative SSI (P<0.001). Conclusions: Thirty seven percent of IBD patients who received Vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis.
Edward V. Loftus - One of the best experts on this subject based on the ideXlab platform.
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Long-term safety of Vedolizumab for inflammatory bowel disease.
Alimentary pharmacology & therapeutics, 2020Co-Authors: Edward V. Loftus, William J. Sandborn, Silvio Danese, Brian G Feagan, Jeanfrederic Colombel, Remo Panaccione, Bruce E. Sands, Geert R. D'haens, David T. Rubin, Ira ShafranAbstract:Background Vedolizumab, a gut-selective α4 β7 integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). Aim To report the final results from the Vedolizumab GEMINI long-term safety (LTS) study. Methods The phase 3, open-label GEMINI LTS study (initiated May 2009) enrolled patients with UC or CD from four prior clinical trials and Vedolizumab-naive patients. Vedolizumab LTS was evaluated; efficacy and patient-reported outcomes were exploratory endpoints. Results Enrolled patients (UC, n = 894; CD, n = 1349) received Vedolizumab 300 mg IV every 4 weeks; median cumulative exposure was 42.4 months (range: 0.03-112.2) for UC and 31.5 months (range: 0.03-100.3) for CD. Over 8 years, adverse events (AEs) occurred in 93% (UC) and 96% (CD) of patients, with UC (36%) and CD (35%) exacerbations most frequent. Serious AEs were reported for 31% (UC) and 41% (CD) of patients. Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients. There were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy. Of the ten deaths (UC, n = 4; CD, n = 6), two were considered drug-related by local investigators (West Nile virus infection-related encephalitis and hepatocellular carcinoma). Continuous Vedolizumab maintained clinical response long-term, with 33% (UC) and 28% (CD) of patients in clinical remission at 400 treatment weeks. Conclusions The safety profile of Vedolizumab remains favourable with no unexpected or new safety concerns. These results further establish the safety of Vedolizumab and support its long-term use (NCT00790933/EudraCT 2008-002784-14).
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Vedolizumab in the Perioperative Management of Inflammatory Bowel Disease.
Current drug targets, 2019Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Edward V. Loftus, Laura E. RaffalsAbstract:BACKGROUND The isolated effect of Vedolizumab on increased postoperative complications remains debated, similar to the controversial data on anti-TNF and postoperative complications. OBJECTIVE To determine the risk of Vedolizumab on postoperative complications. METHODS A review of the literature available to date on studies comparing postoperative outcomes in Vedolizumab-treated versus non-Vedolizumab-treated patients was performed. Studies were stratified by those which combined all inflammatory bowel disease together, those specifically focusing on Crohn's disease or ulcerative colitis individually, and those which included pediatric patients alone. RESULTS The data remains controversial in both the adult and pediatric literature regarding the association of Vedolizumab and increased postoperative complications. The strongest association between Vedolizumab and an increased risk of postoperative infectious complications seems to be in the Crohn's disease literature. CONCLUSION Vedolizumab may be associated with an increased risk of postoperative infectious complications in Crohn's disease, but the literature remains controversial due to difficulty in isolating the effect of the biologic alone in a chronically ill, heterogeneous patient population who are on multiple medications including corticosteroids.
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postoperative outcomes in Vedolizumab treated crohn s disease patients undergoing major abdominal operations
Alimentary Pharmacology & Therapeutics, 2018Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS Twenty-six per cent of Crohn's disease patients who received Vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While Vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.
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Postoperative outcomes in Vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.
Alimentary pharmacology & therapeutics, 2017Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P
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the safety of Vedolizumab for ulcerative colitis and crohn s disease
Gut, 2017Co-Authors: Jeanfrederic Colombel, William J. Sandborn, Silvio Danese, Serap Sankoh, Remo Panaccione, Edward V. Loftus, Bruce E. Sands, Paul Rutgeerts, Geert Dhaens, I FoxAbstract:Objective Vedolizumab is a gut-selective antibody to α 4 β 7 integrin for the treatment of ulcerative colitis (UC) and Crohn9s disease (CD). We report an integrated summary of the safety of Vedolizumab. Design Safety data (May 2009–June 2013) from six trials of Vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of Vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of Vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with Vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p Conclusions Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. Trial registration number NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933.
Kellie L. Mathis - One of the best experts on this subject based on the ideXlab platform.
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postoperative outcomes in Vedolizumab treated patients undergoing major abdominal operations for inflammatory bowel disease retrospective multicenter cohort study
Inflammatory Bowel Diseases, 2018Co-Authors: Amy L. Lightner, Bo Shen, Parambir S Dulai, John H. Pemberton, Kellie L. Mathis, Gursimran Kochhar, Chung Sang Tse, Amandeep Singh, Samuel Eisenstein, William J. SandbornAbstract:Background Vedolizumab is now widely available for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). We sought to quantify the rates of postoperative complications with preoperative Vedolizumab compared with anti-tumor necrosis factor (anti-TNF) therapy. Methods A multicenter retrospective review of adult inflammatory bowel disease (IBD) patients who underwent an abdominal operation between May 20, 2014, and December 31, 2015, was performed. The study cohort was comprised of patients who had received Vedolizumab within 12 weeks of their abdominal operation, and the control cohort was IBD patients who had received anti-TNF therapy. Results A total of 146 patients received Vedolizumab within 12 weeks before an abdominal operation (64% female; n = 93; median age, 33 years; range, 15-74 years), and 289 patients received anti-TNF therapy (49% female; n = 142; median age, 36 years; range, 17-73 years). Vedolizumab-treated patients were younger (P = 0.015) and were more likely to have taken corticosteroids (P < 0.01) within the 12 weeks before surgery. Vedolizumab-treated patients had a significantly increased risk of any postoperative surgical site infection (SSI; P < 0.01), superficial SSI (P < 0.01), deep space SSI (P = 0.39), and mucocutaneous separation of the diverting stoma (P < 0.00) as compared with patients taking anti-TNF therapy. On multivariate analysis, after adjusting for body mass index, steroids at the time of operation, and institution, exposure to Vedolizumab remained a significant predictor of postoperative SSI (P < 0.01). Conclusions We observed that Vedolizumab-treated patients were at significantly increased risk of postoperative SSIs after a major abdominal operation, as compared with anti-TNF-treated patients.
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postoperative outcomes in Vedolizumab treated crohn s disease patients undergoing major abdominal operations
Alimentary Pharmacology & Therapeutics, 2018Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS Twenty-six per cent of Crohn's disease patients who received Vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While Vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.
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Postoperative outcomes in Vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.
Alimentary pharmacology & therapeutics, 2017Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P
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postoperative outcomes in Vedolizumab treated patients undergoing abdominal operations for inflammatory bowel disease
Journal of Crohns & Colitis, 2017Co-Authors: Amy L. Lightner, John H. Pemberton, Laura E. Raffals, Kellie L. Mathis, Chung Sang Tse, Robert R Cima, Eric J Dozois, Edward V. LoftusAbstract:Introduction: Vedolizumab was recently FDA approved for treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). No study to date has examined the rate of postoperative infectious complications among patients who received Vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among IBD patients who received Vedolizumab within 12 weeks of an abdominal operation as compared to patients who received TNFα inhibitors or no biologic therapy. Methods: A retrospective chart review between 5/1/2014 and 12/31/2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort was comprised of patients who received Vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNFα inhibitors or no biologic therapy. Results: 94 patients received Vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications (53%), 35 of which were surgical site infections (SSIs) (36%). The Vedolizumab group experienced significantly higher rates of any postoperative infection (53% vs 33% anti-TNF and 28% non-biologic; P<0.001) and SSI (37% vs 10% and 13%; P< 0.001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative SSI (P<0.001). Conclusions: Thirty seven percent of IBD patients who received Vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis.
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Surgical Outcomes in Vedolizumab-Treated Patients with Ulcerative Colitis.
Inflammatory bowel diseases, 2017Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Sara B. Moncrief, John H. Pemberton, Laura E. Raffals, Kellie L. MathisAbstract:Background Surgical outcomes and pouch outcomes in the setting of Vedolizumab remains poorly understood. We sought to determine the rate of 30-day postoperative surgical infectious complications and pouch-specific complications among patients with ulcerative colitis (UC) who received Vedolizumab within 12 weeks of surgery. Methods A retrospective chart review between 5/1/2014 and 12/31/2016 of all adult patients with UC who underwent an abdominal operation was performed. Patients with UC who received Vedolizumab within 12 weeks of their abdominal operation were compared with patients with UC on anti-TNFα treatment. Results Eighty-eight patients received Vedolizumab and 62 received anti-TNFα within 12 weeks of surgery. More Vedolizumab-treated patients had superficial surgical site infections (P = 0.047) and mucocutaneous separation at the ileostomy (P = 0.047), but there was no difference in the overall surgical infectious complication rate, deep space SSI, 30-day hospital readmission or return to the operating room. On univariate analysis of SSI among patients with UC, exposure to Vedolizumab was not a significant predictor of SSI (P = 0.27), but steroids were predictive of SSI on univariate (P = 0.02) and multivariable analysis (P = 0.02). After ileal pouch anal anastomosis, there was a higher rate of intra-abdominal abscesses (31.3% versus 5.9%) and mucocutaneous separation (18.8% versus 0%) in the Vedolizumab group compared with the anti-TNFα group, but statistical significance was not reached. Conclusions Vedolizumab patients had significantly increased rates of superficial SSI, but not overall infectious complications. Among ileal pouch anal anastomosis patients, peripouch abscess rates were increased among Vedolizumab-treated patients, but this did not reach statistical significance. Vedolizumab seems safe in the perioperative period for patients with UC.
Laura E. Raffals - One of the best experts on this subject based on the ideXlab platform.
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Vedolizumab in the Perioperative Management of Inflammatory Bowel Disease.
Current drug targets, 2019Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Edward V. Loftus, Laura E. RaffalsAbstract:BACKGROUND The isolated effect of Vedolizumab on increased postoperative complications remains debated, similar to the controversial data on anti-TNF and postoperative complications. OBJECTIVE To determine the risk of Vedolizumab on postoperative complications. METHODS A review of the literature available to date on studies comparing postoperative outcomes in Vedolizumab-treated versus non-Vedolizumab-treated patients was performed. Studies were stratified by those which combined all inflammatory bowel disease together, those specifically focusing on Crohn's disease or ulcerative colitis individually, and those which included pediatric patients alone. RESULTS The data remains controversial in both the adult and pediatric literature regarding the association of Vedolizumab and increased postoperative complications. The strongest association between Vedolizumab and an increased risk of postoperative infectious complications seems to be in the Crohn's disease literature. CONCLUSION Vedolizumab may be associated with an increased risk of postoperative infectious complications in Crohn's disease, but the literature remains controversial due to difficulty in isolating the effect of the biologic alone in a chronically ill, heterogeneous patient population who are on multiple medications including corticosteroids.
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postoperative outcomes in Vedolizumab treated crohn s disease patients undergoing major abdominal operations
Alimentary Pharmacology & Therapeutics, 2018Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS Twenty-six per cent of Crohn's disease patients who received Vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While Vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.
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Postoperative outcomes in Vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.
Alimentary pharmacology & therapeutics, 2017Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Laura E. Raffals, Edward V. Loftus, Chung Sang Tse, Kellie L. MathisAbstract:BACKGROUND Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of Vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM We sought to compare 30-day postoperative infectious complication rate among Vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS A retrospective review of all Crohn's disease patients who received Vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS One hundred Crohn's disease patients received Vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two Vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The Vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P
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postoperative outcomes in Vedolizumab treated patients undergoing abdominal operations for inflammatory bowel disease
Journal of Crohns & Colitis, 2017Co-Authors: Amy L. Lightner, John H. Pemberton, Laura E. Raffals, Kellie L. Mathis, Chung Sang Tse, Robert R Cima, Eric J Dozois, Edward V. LoftusAbstract:Introduction: Vedolizumab was recently FDA approved for treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). No study to date has examined the rate of postoperative infectious complications among patients who received Vedolizumab in the perioperative period. We sought to determine the 30-day postoperative infectious complication rate among IBD patients who received Vedolizumab within 12 weeks of an abdominal operation as compared to patients who received TNFα inhibitors or no biologic therapy. Methods: A retrospective chart review between 5/1/2014 and 12/31/2015 of adult IBD patients who underwent an abdominal operation was performed. The study cohort was comprised of patients who received Vedolizumab within 12 weeks of their abdominal operation and the control cohorts were patients who received TNFα inhibitors or no biologic therapy. Results: 94 patients received Vedolizumab within 12 weeks of an abdominal operation. Fifty experienced postoperative complications (53%), 35 of which were surgical site infections (SSIs) (36%). The Vedolizumab group experienced significantly higher rates of any postoperative infection (53% vs 33% anti-TNF and 28% non-biologic; P<0.001) and SSI (37% vs 10% and 13%; P< 0.001). On univariate and multivariate analysis, exposure to Vedolizumab remained a significant predictor of postoperative SSI (P<0.001). Conclusions: Thirty seven percent of IBD patients who received Vedolizumab within 30 days of a major abdominal operation experienced a 30-day postoperative SSI, significantly higher than patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained the only predictor of 30-day postoperative SSI on multivariate analysis.
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Surgical Outcomes in Vedolizumab-Treated Patients with Ulcerative Colitis.
Inflammatory bowel diseases, 2017Co-Authors: Amy L. Lightner, Nicholas P. Mckenna, Sara B. Moncrief, John H. Pemberton, Laura E. Raffals, Kellie L. MathisAbstract:Background Surgical outcomes and pouch outcomes in the setting of Vedolizumab remains poorly understood. We sought to determine the rate of 30-day postoperative surgical infectious complications and pouch-specific complications among patients with ulcerative colitis (UC) who received Vedolizumab within 12 weeks of surgery. Methods A retrospective chart review between 5/1/2014 and 12/31/2016 of all adult patients with UC who underwent an abdominal operation was performed. Patients with UC who received Vedolizumab within 12 weeks of their abdominal operation were compared with patients with UC on anti-TNFα treatment. Results Eighty-eight patients received Vedolizumab and 62 received anti-TNFα within 12 weeks of surgery. More Vedolizumab-treated patients had superficial surgical site infections (P = 0.047) and mucocutaneous separation at the ileostomy (P = 0.047), but there was no difference in the overall surgical infectious complication rate, deep space SSI, 30-day hospital readmission or return to the operating room. On univariate analysis of SSI among patients with UC, exposure to Vedolizumab was not a significant predictor of SSI (P = 0.27), but steroids were predictive of SSI on univariate (P = 0.02) and multivariable analysis (P = 0.02). After ileal pouch anal anastomosis, there was a higher rate of intra-abdominal abscesses (31.3% versus 5.9%) and mucocutaneous separation (18.8% versus 0%) in the Vedolizumab group compared with the anti-TNFα group, but statistical significance was not reached. Conclusions Vedolizumab patients had significantly increased rates of superficial SSI, but not overall infectious complications. Among ileal pouch anal anastomosis patients, peripouch abscess rates were increased among Vedolizumab-treated patients, but this did not reach statistical significance. Vedolizumab seems safe in the perioperative period for patients with UC.
