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BACKGROUND: The evidence regarding the association of preoperative biologic exposure and postoperative outcomes remains controversial for both antitumor necrosis factor agents and vedolizumab and largely unknown for ustekinumab. OBJECTIVE: The purpose of this study was to determine differences in the rates of 30-day postoperative overall infectious complications and intra-abdominal septic complications among the 3 classes of biologic therapies as compared with no biologic therapy. DESIGN: This was a retrospective review. SETTINGS: The study was conducted at an IBD referral center. PATIENTS: Adult patients with Crohn’s disease who received an antitumor necrosis factor, vedolizumab, ustekinumab, or no biologic therapy within 12 weeks of a major abdominal operation between May 20, 2014, and December 31, 2017, were included. MAIN OUTCOMES MEASURES: Thirty-day overall postoperative infectious complications and intra-abdominal septic complications were measured. RESULTS: A total of 712 patients with Crohn’s disease were included; 272 patients were exposed to an antitumor necrosis factor agents, 127 to vedolizumab, 38 to ustekinumab, and 275 to no biologic therapy within the 12 weeks before an abdominal operation. Patients exposed to a biologic were more likely to be taking a concurrent immunomodulator, but there was no difference in concurrent corticosteroid usage. The particular class of biologic was not independently associated with total overall infectious complications. Vedolizumab was associated with an increased rate of intra-abdominal sepsis on univariate analysis but not on multivariable analysis. Combination immunosuppression was associated with both an increased rate of overall postoperative infectious complications and intra-abdominal sepsis. LIMITATIONS: The study was limited by its retrospective design and single-center data. CONCLUSIONS: The overall rate of total infectious complications or intra-abdominal septic complications was not increased based on preoperative exposure to a particular class of biologic. Rates increased with combination immunosuppression of biologic therapy with corticosteroids and previous abdominal resection. See Video Abstract at http://links.lww.com/DCR/B24. BIOLÓGICOS Y COMPLICACIONES POSTOPERATORIAS DE 30 DÍAS DESPUÉS DE LAS OPERACIONES ABDOMINALES PARA LA ENFERMEDAD DE CROHN: ¿EXISTEN DIFERENCIAS EN LOS PERFILES DE SEGURIDAD?: ANTECEDENTES: La evidencia sobre la asociación de la exposición biológica preoperatoria y los resultados postoperatorios sigue siendo controvertida controversial tanto para los agentes del factor de necrosis tumoral (anti-TNF) como para el vedolizumab, y en gran parte desconocida para el ustekinumab. OBJETIVO: Determinar las diferencias en las tasas de complicaciones infecciosas generales postoperatorias de 30 días y complicaciones sépticas intraabdominales entre las tres clases de terapias biológicas en comparación con ninguna terapia biológica. DISEÑO: Revisión retrospectiva. AMBIENTE: centro de referencia de la enfermedad inflamatoria intestinal. PACIENTES: Pacientes adultos con enfermedad de Crohn que recibieron un factor de necrosis antitumoral, vedolizumab, ustekinumab o ningún tratamiento biológico dentro de las 12 semanas de una operación abdominal mayor entre el 5/20/2014 y el 12/31/2017. PRINCIPALES MEDIDAS DE RESULTADOS: Complicaciones infecciosas postoperatorias generales de 30 días, complicaciones sépticas intraabdominales. RESULTADOS: Se incluyeron setecientos doce pacientes con enfermedad de Crohn; 272 pacientes fueron expuestos a un anti-TNF, 127 a vedolizumab, 38 a ustekinumab y 275 a ninguna terapia biológica dentro de las 12 semanas previas a una operación abdominal. Los pacientes expuestos a un producto biológico tenían más probabilidades de tomar un inmunomodulador concurrente, pero no hubo diferencias en el uso simultáneo de corticosteroides. La clase particular de productos biológicos no se asoció de forma independiente con las complicaciones infecciosas totales. Vedolizumab se asoció con una mayor tasa de sepsis intraabdominal en el análisis univariable, pero no en el análisis multivariable. La inmunosupresión combinada se asoció tanto con una mayor tasa de complicaciones infecciosas postoperatorias generales como con sepsis intraabdominal. LIMITACIONES: Diseño retrospectivo, datos de centro único. CONCLUSIONES: La tasa general de complicaciones infecciosas totales o complicaciones sépticas intraabdominales no aumentó en función de la exposición preoperatoria a una clase particular de productos biológicos. Las tasas aumentaron con la combinación de inmunosupresión de la terapia biológica con corticosteroides y resección abdominal previa. Vea el Resumen del Video en http://links.lww.com/DCR/B24.

Abstract Background We aim to assess the impact of a multidisciplinary inflammatory bowel disease (IBD) conference on the management of patients with complex IBD. Methods Data were collected during each conference from February 2017 through October 2018 with chart review performed at 6 months to determine if conference recommendations were successfully implemented. Results Eighty-five patients were discussed. The presenting diagnosis was changed by 11.8%. Recommendations for further testing, medical therapy, and surgery were successfully implemented in 77.1%, 98.1%, and 88.4%, respectively. Conclusions This study supports the role of IBD multidisciplinary conferences in the management of patients with complex IBD.

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.

BACKGROUND: Limited knowledge exists as to what impact preoperative biologic therapy has on post-operative complications in pediatric patients undergoing abdominal surgery for Crohn's disease (CD). Therefore, we sought to determine the 30-day postoperative infectious complication rate among pediatric CD patients who received biologic therapy within 12 weeks of an abdominal operation. METHODS: A retrospective chart review was performed on pediatric (<18 years of age) CD patients who underwent an abdominal operation between 1/1/2008 and 12/31/2017. Patients were grouped according to whether they received an anti-TNF (infliximab, adalimumab, certolizumab pegol) or no biologic therapy within 12 weeks prior to the operation. The primary outcome was a the overall 30-day postoperative infectious complication rate. Secondary outcomes included 30-day readmission rate and return to the operating room (ROR). RESULTS: A total of 69 pediatric CD patients met inclusion criteria (n = 54 anti-TNF therapy, n = 15 received no biologic therapy). There were no differences between the anti-TNF and no biologic cohorts with respect to demographics or CD characteristics. No significant differences in overall 30-day postoperative infectious complications existed between patients exposed to anti-TNF agents and those with no preoperative exposure, or in its subcategories of surgical infectious complications and non-surgical infectious complications. There was also no difference in the rate of ileus, readmission, or ROR. CONCLUSION(S): Preoperative exposure to anti-TNF biologic therapy does not add to overall or infectious 30-day postoperative morbidity in pediatric CD patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), have a higher risk of Clostridium difficile infection (CDI) than the general population (1). The incidence of CDI is increasing among patients with IBD, and certain UC treatments may be associated with greater risk (1). We report CDI events in the tofacitinib UC clinical program, and the incidence of CDI among patients receiving other treatments for UC. METHODS: For the tofacitinib UC program, rates of CDI (patients with an adverse event [AE] of CDI, Clostridium difficile colitis, or Clostridium test-positive, plus concomitant oral metronidazole or vancomycin, counted once per cohort) are reported for Induction Cohort (patients from an 8-week Phase [P]2 and two 8-week P3 induction studies; placebo or tofacitinib 10 mg twice daily [BID; NCT00787202; NCT01465763; NCT01458951]); Maintenance Cohort (patients from a 52-week maintenance study; placebo or tofacitinib 5 or 10 mg BID [NCT01458574]); and Overall Cohort (all tofacitinib-treated patients in P2/3 induction and maintenance studies and an ongoing, open-label, long-term extension study [as of December 2016; NCT01470612]). Positive Clostridium difficile test at screening was an exclusion criterion for program entry. Overall Cohort incidence rate (IR) was calculated as number of unique patients with events per 100 patient-years (PY). For contextualization, CDI rates among patients receiving other UC medications were obtained from a retrospective cohort study utilizing data from the Truven MarketScan ® Database, an administrative healthcare claims database in the US. Patients with moderately to severely active UC, with either an inpatient or outpatient diagnosis code of CDI, plus a prescription for oral therapy (including metronidazole, vancomycin, and fidaxomicin) within 14 days of CDI diagnosis (observation period: October 1, 2010–September 30, 2015), were included. Truven cohort IRs were calculated as number of patients with events per 100 PY. RESULTS: In the tofacitinib Induction Cohort, CDI occurred in 3 patients (placebo, 1/282 [0.4%]; tofacitinib 10 mg BID, 2/938 [0.2%]). In the Maintenance Cohort, CDI occurred in 3 patients (placebo, 3/198 [1.5%]; tofacitinib 5 or 10 mg BID, 0/394 [0.0%]). In the Overall Cohort of all tofacitinib-treated patients (1,664 PY of follow-up), CDI occurred in 8/1,157 patients (0.7%), with an IR (95% confidence interval [CI]) of 0.48 (0.21, 0.95). Two cases were reported as serious AEs. All were mild (n = 4) or moderate (n = 4) in severity; 6 continued with study treatment, one temporarily discontinued, one permanently discontinued. All CDI cases resolved with treatment. In the Truven Cohort, 160 CDI events occurred during 4,918 PY of follow-up, with an overall CDI IR (95% CI) of 3.25 (2.77, 3.80); of which 116 were CDI-associated hospitalizations (4,936 PY of follow-up). Among patients receiving azathioprine, 6-mercaptopurine, or tumor necrosis factor inhibitors, CDI IRs were 3.23 (2.18, 4.62), 2.31 (1.26, 3.87), and 3.58 (2.95, 4.29), respectively. CONCLUSION(S): In the tofacitinib UC program, CDI rates among patients receiving tofacitinib were similar to or lower than those observed with placebo. The IR among patients receiving tofacitinib was numerically lower than those observed for immunomodulators and tumor necrosis factor inhibitors in the Truven Cohort.

BACKGROUND: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib were demonstrated in Phase (P) 2/3 induction studies (NCT00787202; NCT01465763; NCT01458951), a 52-week, P3 maintenance study (NCT01458574), and are being further investigated in an ongoing, open-label, long-term extension (OLE) study (NCT01470612). This analysis assessed age as a risk factor for adverse events (AEs) in the tofacitinib UC clinical program. METHODS: Analyses of AEs were performed for 2 cohorts: the Maintenance Cohort (patients who received placebo or tofacitinib 5 or 10 mg twice daily in the maintenance study) and the Overall Cohort (all tofacitinib-treated patients in the P2/P3/OLE studies [as of December 2016]), stratified by age (≥65 years vs <65 years). AEs of special interest included serious infections (SIs), opportunistic infections (OIs), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, major adverse cardiovascular events (MACE), and gastrointestinal perforations. Risk factors (based on baseline characteristics) for SIs, OIs, HZ, and NMSC in the Overall Cohort were evaluated using multivariate Cox proportional regression models. RESULTS: AEs occurred in 75.3% (placebo) and 75.9% (tofacitinib) of patients in the Maintenance Cohort, and 82.1% in the Overall Cohort (in which 83.9% received predominantly tofacitinib 10 mg twice daily). Most patients (Maintenance Cohort: 180/198 [90.9%] and 364/394 [92.4%] receiving placebo and tofacitinib, respectively; Overall Cohort: 1,080/1,157 [93.3%]) were aged <65 years. In both the placebo and tofacitinib groups of the Maintenance Cohort, rates of AEs, serious AEs, severe AEs, and discontinuations due to AEs were numerically higher in patients aged ≥65 years (placebo: 83.3%, 11.1%, 11.1%, and 22.2%; tofacitinib: 80.0%, 16.7%, 10.0%, and 16.7%) vs <65 years (placebo: 74.4%, 6.1%, 9.4%, and 18.3%; tofacitinib: 75.5%, 4.4%, 7.1%, and 8.8%). AEs of special interest were generally infrequent in both the placebo and tofacitinib groups of the Maintenance Cohort. In the Overall Cohort, AE, serious AE, and severe AE rates were numerically higher in patients aged ≥65 years (88.3%, 19.5%, and 15.6%) vs <65 years (81.7%, 14.3%, and 12.2%). OI, HZ, malignancies (excluding NMSC), NMSC, and MACE rates were numerically higher in patients aged ≥65 years (3.9%, 14.3%, 2.6%, 5.3%, and 2.6%) vs <65 years (1.7%, 5.0%, 0.6%, 0.7%, and 0.2%); SI and gastrointestinal perforation rates were similar between age groups (≥65 years: 2.6% and 0.0%; <65 years: 2.9% and 0.4%). In multivariate modeling in the Overall Cohort, increasing age (every 10 years) was associated with increased risk of OIs (hazard ratio [95% confidence interval] 1.54 [1.15, 2.08]) and HZ (1.58 [1.34, 1.87]), but not SIs or NMSC (univariate modeling: 1.0 [0.78, 1.27] and 2.31 [1.46, 3.66]). CONCLUSION(S): In the tofacitinib UC program, AE rates were higher among patients aged ≥65 years vs those aged <65 years, regardless of whether they received tofacitinib or placebo. In multivariate analyses, older age was associated with increased OI and HZ risk. Although this is consistent with the general population, due to the small number of patients aged ≥65 years (<10% of the total), these findings should be interpreted with caution.

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.