Faculty Bibliography

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.

BACKGROUND & AIMS/OBJECTIVE:Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBD). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD. METHODS:We conducted a retrospective cohort study, collecting data from 5 medical centers on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission. RESULTS:Our analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD-unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse following a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18-2.71; HR for immunomodulators, 2.22; 95% CI, 1.38-3.55; HR for biologics, 1.95; 95% CI, 1.01-5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21-3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01-3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank=0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission. CONCLUSIONS:In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

BACKGROUND:Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis. Alvimopan, an oral peripherally acting mu-opioid receptor antagonist approved for accelerating gastrointestinal recovery, has never been studied specifically in patients with inflammatory bowel disease (IBD). AIM/OBJECTIVE:To investigate the efficacy of alvimopan in preventing POI among IBD patients. METHODS:A retrospective chart review was conducted on 246 IBD patients undergoing bowel surgery between 2012 and 2017. Data collected included demographics, IBD subtype, length of stay (LOS), postoperative gastrointestinal symptoms, and administration of alvimopan. The primary outcome was POI; secondary gastrointestinal recovery outcomes were: time to first flatus, time to first bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and LOS. RESULTS:When compared with the control group, patients in the alvimopan group had shorter times to tolerating liquids and solids, first flatus, and first bowel movements (p < 0.01). LOS was shorter in the alvimopan group when compared with controls (p < 0.01). The overall incidence of POI was higher in controls than in the alvimopan group (p = 0.07). For laparoscopic surgeries, the incidence of POI was also higher in controls than in the alvimopan group (p < 0.01). On multivariable analysis, alvimopan significantly decreased time to all gastrointestinal recovery endpoints when compared to controls (p < 0.01). CONCLUSIONS:Alvimopan is effective in accelerating time to gastrointestinal recovery and reducing POI in IBD patients. While the benefits of alvimopan have been demonstrated previously, this is the first study of the efficacy of alvimopan in IBD patients.

OBJECTIVE:The objective of this study was to assess if bowel wall iodine density obtained from dual-source, dual-energy computed tomography enterography (DECTE) could be a biomarker of Crohn's disease activity. METHODS:Twenty-two patients with Crohn's disease imaged with DECTE from February 2016 to May 2018 were retrospectively identified by departmental report search. Iodine maps were created with commercial software (Syngovia). Iodine content was normalized to the aorta, and then manual dual-energy region-of-interest cursors were placed over the visibly assessed maximal and minimal iodine density within segments of involved as well as unaffected small bowel. The mixed Hounsfield unit value, maximum iodine density (Imax), and minimum iodine density (Imin) were recorded. The length of affected bowel demonstrating maximum disease activity as a percentage of overall involvement was subjectively assessed. A weighted iodine density (Iweighted) was calculated. The clinical assessment of disease activity using erythrocyte sedimentation rate, C-reactive protein, fecal calprotectin, colonoscopy/endoscopy, and surgery, if available, served as the reference standard. The Crohn's disease activity index was also used as a separate additional reference standard. RESULTS:Significant heterogeneity within the affected segments was present. The average Imax and Imin of affected bowel was 4.27 ± 1.11 (2.4-7.4) mg/mL and 2.71 ± 0.51 (2.2-3.9) mg/mL, respectively. Iodine density of normal-appearing small bowel was 1.40 ± 0.26 (0.9-1.9) mg/mL. The Imax and Imin of affected bowel differed significantly from normal bowel (P < 0.0001). Mixed Hounsfield unit (101.82 ± 27.5) also statistically differed (46.33 ± 19.62) (P < 0.0001). Using overall clinical assessment as the reference standard, all patients with Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, or Imax of greater than 4.7 mg/mL had clinically active disease. Sixteen of 17 patients with Imin of greater than 2.2 mg/mL and 14/15 with Iweighted of greater than 3 mg/mL had clinically active disease. Using Crohn's disease activity index as the reference standard, all patients with Imin of greater than 2.7 mg/mL, Iweighted of greater than 3.6 mg/mL, or Imax of greater than 5.4 mg/mL had clinically active disease. The median effective dose was 4.64 ± 1.68 mSv (range, 2.03-8.12 mSv). CONCLUSIONS:Iodine density obtained from DECTE highlights regions of maximal activity within affected bowel segments. An iodine density of 2 mg/mL appears to be a threshold between normal bowel segments and those with active Crohn's disease. Iodine density measurement thresholds Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, and Imax of greater than 4.7 mg/mL correlate with established clinical markers of disease activity, with Imin seemingly most useful in daily clinical practice.

PURPOSE OF REVIEW/OBJECTIVE:Treating moderate-to-severe inflammatory bowel disease has become increasingly complex as the array of available biologics increases. Moreover, tofacitinib, the first small molecule approved for IBD, is available for use in ulcerative colitis. Choosing the right biologic, for the right patient, at the right time, can be a confusing and daunting task for clinicians. RECENT FINDINGS/RESULTS:In this review, we summarize the evidence for first-line use of the available biologics by disease state. Special circumstances for consideration including rapidity of action, safety, comparative effectiveness, postoperative Crohn's disease, fertility and pregnancy, and extraintestinal manifestations are discussed. In the moderate-to-severe UC patient, vedolizumab and infliximab are preferred first-line options. In the moderate-to-severe CD patient with a penetrating phenotype or with multiple EIMs, infliximab or adalimumab are the preferred first-line agents. In the moderate-to-severe CD patient with an inflammatory phenotype, anti-TNF, vedolizumab, and ustekinumab are all reasonable options.

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.

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.