Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). METHODS: We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. RESULTS: Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. CONCLUSIONS: We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: There are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice. METHODS: We performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs. RESULTS: Our analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections. CONCLUSION: In a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

BACKGROUND & AIMS: Patients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration. METHODS: We analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes. RESULTS: Within 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC. CONCLUSIONS: Patients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC.

Characterization of megapouch in patients with restorative proctocolectomy.

BACKGROUND: Megapouch is a rare functional complication of restorative proctocolectomy with ileal pouch-anal anastomosis characterized by pouch ± small bowel dilatation with no evidence of obstruction on endoscopy and imaging. Little is known about clinical characteristics and outcomes of this entity. METHODS: We included all patients diagnosed with megapouch at our institution, identified from a pouch database. Data on baseline characteristics, management, and outcomes were documented and analyzed from electronic medical records. Appropriate statistical measures were used. p < 0.05 was considered significant. RESULTS: Twenty-three patients with megapouch were identified. The mean age was 40.7 years; 95.6% had underlying ulcerative colitis; most common indication for colectomy was medically refractory disease (56.5%). Abdominal pain (82.6%) and bloating (52.2%) were most common presenting symptoms. Most common finding on pouchoscopy was pouch dilatation (81.8%), while barium or gastrografin enemas and MRI/CT mostly revealed dilatation of pouch and/or small bowel. Fourteen (66.7%) patients required some forms of surgery-six patients required pouch excision and three required either pouch redo or revision. Rates of pouch failure and IBD-related 1-year hospitalization were higher among patients managed surgically versus those managed medically (p = 0.007 and 0.024, respectively), while need for escalation of IBD-therapy was comparable between the groups (p = 0.133). No deaths were reported and no patient had recurrence of megapouch. IPAA revision or redo did not lead to more IBD-related morbidity. CONCLUSIONS: Majority of our patients with megapouch required surgery. In selected patients, redo pouch offered cure. Rates of pouch failure and IBD-related 1-year hospitalization were higher among patients managed surgically.

Efficacy and safety of vedolizumab in elderly patients with inflammatory bowel disease: a matched case-control study.

BACKGROUND: Vedolizumab was demonstrated to be safe and effective in adults with moderately to severely active inflammatory bowel disease (IBD) in clinical trials. However, there are limited data regarding its efficacy and safety in elderly patients. METHODS: This was a case-control study comparing the efficacy (measured by rates of mucosal healing and need for IBD surgery) and safety of vedolizumab in IBD among patients ≥65 years of age (the elderly group) vs those <65 years (the control group). The two groups were matched individually on a 1:4 ratio based on gender and type of IBD. Conditional logistic regression was used for stratified analysis to calculate odds ratios and confidence intervals. RESULTS: We included 25 IBD patients in the elderly group and 100 matched patients in the comparison group. Eighty patients had Crohn's disease and 45 had ulcerative colitis. At baseline, the groups were comparable with regard to duration of IBD, prior anti-TNF therapy, and prior IBD surgery. The rate of mucosal healing on follow-up endoscopy was comparable between the elderly and control groups (50% vs 53%, P = 0.507). Although more patients in the elderly group required IBD-related surgery while on vedolizumab, the difference did not reach statistical significance (40% vs 19%, P = 0.282). Rates of vedolizumab-related adverse effects-rash, arthralgia, infections, infusion reactions, and dyspnea-were comparable between the two groups (all P > 0.05). CONCLUSIONS: In a real-world setting, vedolizumab was demonstrated to have an efficacy and safety profile among elderly IBD patients that were comparable to younger controls.

Endoscopic therapy of colorectal anastomotic hematoma with hypertonic dextrose.

Anastomotic dehiscence and leak are dreaded complications after a colorectal resection and can often present with rectal bleeding and pelvic abscess or sepsis. Although most cases of bleeding after gastrointestinal anastomoses are minor and self-limited, major bleeding, as defined by hemodynamic instability or the need for blood transfusions, poses a significant challenge for management. Here we report a case in which a patient presenting with profuse rectal bleeding and pelvic hematoma secondary to a colorectal anastomotic leak was treated endoscopically with 50% dextrose spray then enema.

Changes in Vedolizumab Utilization Across US Academic Centers and Community Practice Are Associated With Improved Effectiveness and Disease Outcomes.

BACKGROUND: Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn's disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. METHODS: We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014-June 2015 (Era 1) and July 2015-June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. RESULTS: A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease-related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. CONCLUSION: Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.