Lightner, Amy L.

BACKGROUND: There is no study to date examining the safety of initiating or restarting biologic therapy after major abdominal surgery for Crohn’s disease. OBJECTIVE: The purpose of this study was to determine differences in the rates of 90-day superficial surgical site infections, intra-abdominal sepsis, and overall postoperative infectious complications among patients who were initiated on or restarted a biologic within 90 days postoperatively compared with those who were not. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at an IBD referral center. PATIENTS: Adult patients with Crohn’s disease who received a biologic therapy within 90 days of a major abdominal operation between May 20, 2014, and December 31, 2018, were included. MAIN OUTCOMES MEASURES: Ninety-day superficial surgical site infection, intra-abdominal sepsis, and overall postoperative infectious complications were measured. RESULTS: A total of 680 patients with Crohn’s disease were included: 351 were initiated on biologic therapy within 90 days after surgery and 329 were not. Patients exposed to biologic therapy postoperatively were younger (p < 0.001), had a lower BMI (p = 0.0014), were less often diabetic (p = 0.0011), and were more often exposed preoperatively to biologics (p < 0.0001) and immunomodulators (p < 0.0001) but not corticosteroids (p = 0.8399). Of those exposed postoperatively, nearly all (93.7%) had been on a biologics preoperatively, and most resumed the same biologic (68.0%). The median time to starting biologic therapy postoperatively was 31 days (range, 7–89 d). Postoperative biologic exposure was not associated with an increased risk of superficial surgical site infection (HR = 1.02 (95% CI, 0.95–1.09) per week; p = 0.59), intra-abdominal sepsis (HR = 1.07 (95% CI, 0.99–1.16); p = 0.73), or overall postoperative infectious complications (HR = 1.02 (95% CI, 0.98–1.07); p = 0.338); the overall rates of each at 90 days was 13%, 8%, and 28%. LIMITATIONS: The study was limited by its retrospective design and single-center data. CONCLUSIONS: Postoperative initiation or resumption of biologic therapy did not increase 90-day rates of superficial surgical site infection, intra-abdominal sepsis, or total infectious complications after major abdominal surgery for Crohn’s disease. See Video Abstract at http://links.lww.com/DCR/B207. ¿SON SEGUROS LOS FÁRMACOS BIOLÓGICOS EN EL POSTOPERATORIO INMEDIATO? UNA EVALUACIÓN DE UN SOLO CENTRO DE PACIENTES QUIRÚRGICOS CONSECUTIVOS CON ENFERMEDAD DE CROHN ANTECEDENTES: No hay ningún estudio hasta la fecha que examine la seguridad de iniciar o reiniciar la terapia biológica después de una cirugía abdominal mayor en enfermedad de Crohn. OBJETIVO: Determinar las diferencias en las tasas a 90 días de infecciones del sitio quirúrgico superficial, sepsis intraabdominal y complicaciones infecciosas postoperatorias generales entre los pacientes en que se inició o reinició un biológico dentro de los 90 días después de la operación en comparación con aquellos que no lo recibieron. DISEÑO: Estudio de cohorte retrospectivo. ESCENARIO: Centro de referencia de enfermedad inflamatoria intestinal. PACIENTES: Pacientes adultos con enfermedad de Crohn que recibieron una terapia biológica dentro de los 90 días de una operación abdominal mayor entre el 20 de mayo de 2014 y el 31 de diciembre de 2018. PRINCIPALES MEDIDAS DE RESULTADO: Infección superficial del sitio quirúrgico, sepsis intraabdominal y complicaciones infecciosas postoperatorias generales a 90 días. RESULTADOS: Se incluyeron un total de 680 pacientes con enfermedad de Crohn: 351 se iniciaron en terapia biológica dentro de los 90 días posteriores a la cirugía y 329 no. Los pacientes expuestos a terapia biológica después de la operación eran más jóvenes (p <0.001), tenían un índice de masa corporal más bajo (p = 0.0014), eran con menos frecuencia diabéticos (p = 0.0011) y estaban expuestos con mayor frecuencia preoperatoriamente a fármacos biológicos (p <0.0001) e inmunomoduladores (p <0.0001) pero no a corticosteroides (p = 0.8399). De los expuestos postoperatoriamente, casi todos (93.7%) habían estado en terapia biológica en el preoperatorio, y la mayoría reanudó la misma terapia biológica (68%). La mediana de tiempo para comenzar la terapia biológica después de la operación fue de 31 días (rango, 7-89 días). La exposición biológica postoperatoria no se asoció con un mayor riesgo de infección superficial del sitio quirúrgico (HR 1.02 (0.95-1.09) por semana, p = 0.59), sepsis intraabdominal. (HR: 1.07 (0.99-1.16), p = 0.73), o complicaciones infecciosas postoperatorias generales (HR: 1.02, intervalo de confianza del 95% 0.98-1.07, p = 0.338); las tasas generales de cada uno a los 90 días fue del 13%, 8% y 28%. LIMITACIONES: Diseño retrospectivo, y datos de un centro único. CONCLUSIONES: El inicio o la reanudación en el postoperatorio de la terapia biológica no aumentaron las tasas a 90 días de infección superficial de sitio quirúrgico, sepsis intraabdominal o complicaciones infecciosas totales después de una cirugía abdominal mayor por enfermedad de Crohn. Consulte el Video Resumen en http://links.lww.com/DCR/B207. (Traducción—Dr Jorge Silva Velazco)

Abstract Background Clinical trials utilizing mesenchymal stem cells (MCSs) for the treatment of perianal Crohn disease are expanding. Most enrolled Crohn patients are being actively treated with corticosteroids, immunomodulators, and biologic therapy for their luminal and perianal disease at the time of enrollment and treatment. Aim We sought to broaden the understanding of the effect of corticosteroids, immunomodulators, and biologic therapy on the viability and function of MCSs. This information is important for tailoring inclusion and exclusion criteria of clinical trials. Methods Human adipose–derived mesenchymal stem cells (hAMCSs) were harvested and isolated from healthy patient donors. At Passage 3, hAMCSs were treated with 7 commonly used immunosuppressive therapies used to treat Crohn disease at increasing concentrations: dexamethasone, methotrexate, azathioprine, 6-mercaptopurine, infliximab, vedolizumab, and ustekinumab. Cell proliferation, migration, and cytokine secretion were analyzed at Day 4. Results Dexamethasone and azathioprine and 6-mercaptopurien affected cell proliferation and migration. Dexamethasone even resulted in cell death at high physiologic concentrations. The same drugs also had the most profound impacts on IL-6, IL-8, and monocyte chemoattractant protein-1 secretion profiles. Biologic therapies, including anti-tumor necrosis factor, anti-interleukin, and anti-integrins, had the smallest impact on hAMSC proliferation, migration, and cytokine secretion profile. Conclusions In clinical trials with MCSs, a washout period may be recommended for corticosteroids and immunomodulators to minimize any effect of systemic immunosuppression on MSC function and efficacy.

BACKGROUND: After IPAA, 8% of patients with ulcerative colitis are later diagnosed with Crohn’s disease of the pouch, associated with an increased rate of pouch failure. No study has reported on how often the clinical diagnosis is correlated with histologic findings of Crohn’s disease in the excised pouch. OBJECTIVE: The purpose of this study was to determine whether the clinical diagnosis is consistent with pathologic confirmation at pouch excision. SETTINGS: The study was conducted at a tertiary IBD referral center. PATIENTS: Patients with chronic ulcerative colitis who underwent pouch excision for presumed Crohn’s disease of the pouch were included. MAIN OUTCOME MEASURES: Preoperative evaluation and pathologic variables at the time of pouch excision were measured. RESULTS: A total of 35 patients underwent pouch excision for Crohn’s disease of the pouch based on a combination of clinical, radiographic, and endoscopic findings. Seven (20%) had surgical pathology consistent with Crohn’s disease at pouch excision. There were no differences in those 7 patients and the remaining 28 in terms of diagnosis at colectomy, primary pouch symptoms, prepouch inflammation, ulceration, or granulomas at endoscopy. In the nonpathology-confirmed Crohn’s disease, 40% (n = 11) had an anastomotic leak at time of IPAA versus 0% in the Crohn’s disease group, and 86% (n = 24) had symptoms of pouch dysfunction within 5 months of ileostomy reversal versus 13 months in the Crohn’s disease group. Of 28 without pathology-confirmed Crohn’s disease, 100% (n = 28) were treated with antibiotics, 68% (n = 19) with steroids, 59% (n = 16) with immunomodulators, and 57% (n = 15) with biologic therapy for Crohn’s disease of the pouch. LIMITATIONS: The study was limited by its single-center scope and lack of an established definition for Crohn’s disease of the pouch. CONCLUSIONS: Pathologic confirmation of Crohn’s disease was given to only one fifth of patients who underwent pouch excision for Crohn’s disease of the pouch. Given the histologic variability in Crohn’s disease, it may be unreasonable to expect histologic confirmation in every case; still, the diagnosis of Crohn’s disease of the pouch may be overly ascribed, resulting in unnecessary immunosuppressive medications and exclusion from consideration for pouch reconstructive surgery. See Video Abstract at http://links.lww.com/DCRA432.