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.

Presentation and outcomes among inflammatory bowel disease patients with concurrent pneumatosis intestinalis: a case series and systematic review.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) involves chronic inflammation of the colon with ulcerative colitis (UC), and the colon and/or small intestine with Crohn's disease (CD). Pneumatosis intestinalis (PI), characterized by compromise of the intestinal wall with gas-filled cysts, has rarely been reported with IBD. The presentation, best management and outcomes of PI with IBD are poorly defined. METHODS: We conducted a search for PI in all abdominal computed tomography (CT) reports at 2 large tertiary care hospitals from January 1, 2010 to December 31, 2017, cross referenced to ICD codes for IBD. CT and chart review was performed to confirm PI and IBD respectively. A systematic review excluding case reports was performed for PI with IBD for comparison. RESULTS: Of 5,990 patients with a CT abdomen report mentioning PI, we identified 11 cases of PI with IBD, 4 UC, 6 CD, and 1 indeterminate colitis. PI was limited to the small bowel in 5 patients, the right colon in 5, and small bowel and colonic in 1. All 3 mortalities had CD, small intestinal PI and portal/mesenteric venous gas. The systematic literature search identified 9 articles describing 58 patients with IBD and PI. These cases were mostly included in larger cohorts of PI patients without extractable data on presentation or outcomes in the IBD subpopulation. CONCLUSIONS: Ours appears to be the first reporting of presentations and outcomes, outside of case reports, for those with PI and IBD. The high mortality for those with CD and PI of the small bowel appears to define a group requiring more than supportive medical care.

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.

Analysis of the clinical indications for opiate use in inflammatory bowel disease.

BACKGROUND/AIMS: Opiate use for inflammatory bowel disease (IBD), particularly high-dose (HD) use, is associated with increased mortality. It's assumed that opiate use is directly related to IBD-related complaints, although this hasn't been well defined. Our goal was to determine the indications for opiate use as a first step in developing strategies to prevent or decrease opiate use. METHODS: A retrospective cohort was formed of adults who were diagnosed with IBD and for whom outpatient evaluations from 2009 to 2014 were documented. Opiate use was defined if opiates were prescribed for a minimum of 30 days over a 365-day period. Individual chart notes were then reviewed to determine the clinical indication(s) for low-dose (LD) and HD opiate use. RESULTS: After a search of the electronic records of 1,109,277 patients, 3,226 patients with IBD were found. One hundred four patients were identified as opiate users, including 65 patients with Crohn's and 39 with ulcerative colitis; a total of 134 indications were available for these patients. IBD-related complaints accounted for 49.25% of the opiate indications, with abdominal pain (23.13%) being the most common. Overall, opiate use for IBD-related complaints (81.40% vs. 50.82%; P=0.0014) and abdominal pain (44.19% vs. 19.67%; P=0.0071) was more common among HD than among LD. CONCLUSIONS: Our findings show that most IBD patients using opiates, particularly HD users, used opiates for IBD-related complaints. Future research will need to determine the degree to which these complaints are related to disease activity and to formulate non-opiate pain management strategies for patients with both active and inactive IBD.