Loftus, Edward V.

Abstract Introduction The impact of ustekinumab on adverse postoperative outcomes in Crohn’s disease (CD) remains largely unknown. We determined the difference in 90-day postoperative complication rates among CD patients exposed to ustekinumab within 12 weeks prior to an abdominal operation as compared to patients not exposed to biologic therapy. Methods A retrospective chart review of all adults with CD who underwent an abdominal operation between October 1, 2017 and December 31, 2018 at a single tertiary medical center was performed. Data collection included patient demographics, concurrent immunosuppression, serum laboratory values, operative values, and 90-day outcomes including superficial surgical site infection (sSSI), intra-abdominal sepsis, overall infectious complications, readmission, and reoperation rates. The primary outcome was the 90-day rate of intra-abdominal sepsis. Results Fifty-seven CD patients received ustekinumab and 277 received no biologic therapy in the 12 weeks prior to major abdominal surgery. Ustekinumab-exposed patients were younger, less likely to have diabetes mellitus or active tobacco exposure, were more often obese, and more often taking a concurrent immunomodulator. Ustekinumab remained an independent predictor of intra-abdominal sepsis on multivariable logistic regression. Immunomodulator exposure was associated with significantly increased rates of sSSI and overall complication rates. Conclusions Ustekinumab is associated with increased rates of 90-day postoperative intra-abdominal sepsis following a major abdominal operation for CD.

Abstract Background and study aims There are limited published data on endoscopic removal of colorectal polyps by endoscopic mucosal resection (EMR) and endoscopic mucosal dissection (ESD) in patients with inflammatory bowel disease (IBD). Patients and methods We performed a retrospective review of patients with colonic IBD and colonic polyps >10mm who underwent EMR and/or ESD at our institution between January 1, 2012 and June 31, 2016. Results Ninety-seven patients with pathology-confirmed IBD (median disease duration 16 years) were included. Mild or moderate active colitis (in background biopsies) was seen in 85 %. Of the total 124 polyps, location was ascending colon in 44 %, transverse in 15 % and sigmoid in 18.5 %; of the total, 55 % were < 20 mm and 45 % were ≥20mm in maximal diameter. Using the Paris classification, 56 % of polyps were polypoid sessile (Is) polyps, while 38 % were non-polypoid (IIa, IIb, IIc). EMR was used in 118 polyps, three required ESD, and three by combined EMR-ESD. Seventy-two percent were resected en-bloc; 28 % underwent piecemeal resection. Histology included low-grade dysplasia in 75, serrated adenoma in 31, and tubular adenoma in 14 polyps. Chromoendoscopy was used in 33 (26.6 %). Adverse events occurred in three patients. Colectomy was performed in 11 patients within 12 months. Recurrence was seen in 20 polyps, 11 of which were successfully resected en-bloc using EMR. Polyps ≥ 20 mm and polyps treated with APC were found to have a statistically significantly higher risk of recurrence. Conclusion This study demonstrates the efficacy and safety of endoscopic resection of large polyps in patients with IBD, making them effective alternatives to colectomy.

Background and aims: Patient-reported outcomes (PROs) will become increasingly important as primary endpoints in future clinical trials. We aimed to evaluate the relationship between health-related quality of life (HRQoL) and the combination of patient-reported clinical symptoms (ClinPRO2) and Mayo endoscopic subscore (MES) in patients with ulcerative colitis (UC). Methods: We conducted a prospective cross-sectional study of 90 consecutive UC patients who were scheduled for sigmoidoscopy or colonoscopy. All patients completed the following questionnaires: (1) self-rated rectal bleeding and stool frequency (ClinPRO2); (2) Short Inflammatory Bowel Disease Questionnaire (SIBDQ); (3) European Quality of Life 5-Dimensions 3-Level (EQ5D3L); (4) Work Productivity and Activity Impairment questionnaire (WPAI); (5) Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); and (6) Hospital Anxiety and Depression Scale (HADS). The endoscopic images were graded according to the MES. “No symptoms” was defined as a symptom score of 0, and “mucosal healing” was defined as MES score of 0–1. Correlations between the combined ClinPRO2 and MES with HRQoL were assessed using Spearman’s correlation coefficients. Results: The combination of the ClinPRO2 and MES was well correlated to SIBDQ (r = −0.70), EQ5D3L (r = −0.51), WPAI (r = 0.62), FACIT-F (r = −0.58), and HADS-depression (r = 0.45). SIBDQ scores had strong correlations with FACIT-F (r = 0.86), WPAI (r = −0.80), and HADS-depression (r = −0.75) (p < 0.05 for all correlations). Patients with no symptoms reported the greatest all HRQoL scores. Conclusions: In patients with ulcerative colitis, the combination of a ClinPRO2 and the MES had good correlation with the SIBDQ. In addition, SIBDQ was well correlated to the various HRQoL.

Abstract Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Abstract 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.

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. Method:: 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.