Prophylactic versus endoscopy-driven treatment of Crohn's postoperative recurrence: A retrospective, multicentric European study (PORCSE study).

BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence (POR) after ileocecal resection (ICR) for Crohn's disease (CD).We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD-patients undergoing first ICR were assigned to cohort1 if a biologic or immunomodulator was (re)started prophylactically after ICR, or to cohort2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR (Rutgeerts>i1). Secondary endpoints were severe endoscopic POR (Rutgeerts i3/i4), clinical POR, surgical POR and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment (proactive/cohort1) and 52.6% did not (reactive/cohort2).Endoscopic POR (Rutgeerts>i1) rate was significantly higher in cohort2 (41.5% vs 53.8%, OR1.81, P=0.039) at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found (OR1.29, P=0.517). Cohort2 had significantly higher clinical POR rates (17.7% vs 35.7%, OR3.05, P=0.002) and numerically higher surgical recurrence rates (6.7% vs 13.2%, OR2.59, P=0.051). Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach (HR2.50, P=0.057). Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in cohort2 (mean ratio 0.53, P=0.002), but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared to expectant management after first ileocecal resection for Crohn's disease.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Chronic gut inflammation in Crohn's disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

Memory T Cell Subpopulations as Early Predictors of Remission to Vedolizumab in Ulcerative Colitis.

Background: Vedolizumab is a humanized monoclonal antibody targeting the α4ß7 integrin used for the treatment of ulcerative colitis. Few biomarkers related to vedolizumab response have been identified. The aim of this work was to assess whether baseline circulating CD4+ and CD8+ memory T-lymphocyte subpopulations could help to identify patients with response to vedolizumab treatment in ulcerative colitis. Methods: Prospective pilot study in 15 patients with active ulcerative colitis and previous failure to anti-TNFα starting vedolizumab treatment. Peripheral blood samples were obtained before the first dose of vedolizumab and at week 6 and 14 of treatment. Clinical remission was defined as a Mayo Clinic partial score of ≤2 points without any concomitant dose of steroids. Biochemical remission or endoscopic improvement was defined as fecal calprotectin <250 mcg/g or Mayo endoscopic subscore ≤1. Results: At week 14, nine patients achieved clinical remission and eight patients achieved biochemical remission or endoscopic improvement. Patients in clinical remission presented higher baseline CD8 α4ß7 + memory T cells concentration when compared with patients with no remission. In addition, patients with biochemical remission or endoscopic improvement at week 14 presented higher baseline concentration of CD8 α4ß7 + memory T cells. No differences were identified according to flare severity, extent of disease or type of anti-TNFα failure. There were no significant differences regarding changes in T cell subsets during vedolizumab induction. Conclusion: CD8+ α4ß7 + memory T cells before starting vedolizumab therapy could be an early predictor of remission in ulcerative colitis patients and therefore help to select a subset of responders.

Management and Long-term Outcomes of Crohn's Disease Complicated with Enterocutaneous Fistula: ECUFIT Study from GETECCU.

BACKGROUND AND AIMS: Crohn's disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. METHODS: Clinical information from all adult patients with CD and at least one ECF-excluding perianal fistulae-were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. RESULTS: A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. CONCLUSIONS: ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

Is Flexible Ureteroscopy and Laser Lithotripsy the New Gold Standard for Pediatric Lower Pole Stones? Outcomes from Two Large European Tertiary Pediatric Endourology Centers.

Introduction: Although pediatric ureteroscopy has been increasingly performed, the evidence for its use in pediatric lower pole stones (LPS) is sparce. In this study we look at the effectiveness and outcomes of flexible ureteroscopy and laser lithotripsy (FURSL) in the management of LPS for a pediatric population. Materials and Methods: Data were collected from two large European tertiary endourology centers that specialize in pediatric kidney stone management. The study was registered as an audit at the respective hospitals. All data were cross-checked and analyzed using electronic operative notes, discharge records, laboratory systems, and patient correspondence. The inclusion criteria were patients ≤16 years with LPS having an FURSL procedure. Results: A total of 57 pediatric patients underwent FURSL for LPS. The mean age was 10.1 ± 4.7 years (range: 1-16.9 years) with a male-female ratio of 2:3. The mean single stone size was 9.45 ± 3.9 mm (range: 3-20 mm) and 31 (54.4%) had multiple stones. A preoperative stent was present in 18 (31.6%) patients and a postoperative stent or ureteral catheter was left behind in 32 (56.1%) patients. The initial and final stone-free rates were 82.4% and 98.2%, respectively, with 1.19 procedures per patient performed to be stone free. Although there were no intraoperative complications, there were only four (7%) minor complications (Clavien I) noted that were all simple urinary infections. No long-term complications were noted. Conclusion: Flexible ureteroscopy and lasertripsy achieve excellent outcomes for treatment of pediatric LPS. Although some patients might need a second procedure for complete stone clearance, FURSL may be considered as the first-line treatment of LPS.

Oral Acidification with l-Methionine as a Noninvasive Treatment for Encrusted Uropathy.

Background: Encrusted uropathy (EU) is a rare disease caused by urea-splitting bacteria, most commonly Corynebacterium urealyticum, whose incidence is increasing. Standard treatment is based on pathogen-directed antibiotic therapy, urinary diversion, bladder instillations, and surgical resection of urinary calcifications. Case Presentation: We present the case of a 60-year-old man with symptomatic bilateral encrusted pyelitis and cystitis with acute renal failure. We initially treated the patient with antibiotic therapy, urinary diversion, and oral acidification with acetohydroxamic acid, achieving negative urinary cultures. Because of the persistence of encrusted pyelitis, the patient was discharged on oral l-methionine 500 mg bid and 12 months later the encrustations had almost disappeared. Finally, we performed right retrograde intrarenal surgery to remove a persistent small calcification. Conclusion: Oral urinary acidification with l-methionine is a valid treatment for urinary encrustations in EU, with no complications reported. Complete resolution of the calcifications may be achieved without the need for invasive processes and unnecessary manipulation of the urinary system.

[Confocal laser endomicroscopy for the treatment of upper urinary tract transitional cellcarcinoma.] / Endomicroscopía láser confocal en el tratamiento del tumor urotelial del tracto urinario superior.

OBJECTIVES: Confocal lasser endomicroscopy (CLE) is an optical technique that enables in vivo cytological characterization of a tissue. Previous studies have shown it useful in the evaluation of urinary and respiratory tracts for a better characterization of mucosal lesions, showing a high concordance between in vivo and final histopathological results. Recently, the use of CLE has been proposed for the study of transitional cell carcinoma of the upper urinary tract (UUT) during ureteroscopy, because it enables real time information about tumor grade and supplements the information of ureteroscopic biopsies, which may understimate the grade and stage of the lesion up to 43% of the cases due to its limitiations. METHODS: We performed a systematic review of the literature in the Pubmed/Medline database following the PRISMA standard. We selected 20 articles that complied with the inclusion criteria for evidence synthesis. RESULTS: Equipment miniaturization has enabled CLE as part of the diagnostic options in upper urinary tract tumors. This technique performs in vivo cytological characterization of the evaluated tissue, accomplishing differentiation between tumor and normal tissue, as well as tumor grade identification. Its communicated sensitivity and specificity reach 79%/78% respectively for low grade tumors and 67%/79% for high grade, with a substantial inter observer concordance (surgeon/pathologist; k = 0.64). No complications have been communicated in the literature with the use of fluorescein or confocal laser microscopy probes in patients undergoing this technique. CONCLUSIONS: CLE represents a useful and safe tool, capable of providing cytological real time information of UUT tumors that enables tumor grade identification with substantial concordance between in vivo tumor typifying and the final histopathological analysis. For this, CLE is currently considered a tool for conservative management of UUT transitional cell carcinoma in the European Association of Urology (EAU) guidelines.

OBJETIVOS: La endomicroscopía láser confocal (CLE) es una técnica óptica que permite la caracterización citológica en vivo de un tejido. Estudios previos en lesiones del tracto digestivo y respiratorio han mostrado una alta concordancia entre el resultado en vivo y el resultado histopatológico. Recientemente, se ha propuesto el uso de la CLE en el estudio del tracto urinario superior (TUS) durante la ureteroscopia, ya que permite obtener información a tiempo real del grado tumoral y complementa la información de las biopsias ureteroscópicas, que dadas sus limitaciones, pueden infraestimar el grado y el estadío de la lesión hasta en un 43% de los casos.MÉTODOS: Se llevó a cabo una revisión de la literatura en la base de datos Pubmed/Medline siguiendo las normas PRISMA. Se utilizaron 21 artículos que cumplieron los criterios de inclusión para la síntesis de la evidencia. RESULTADOS: La sensibilidad y especificidad descrita, alcanza el 79%/78% y 67%/79% para tumores de bajo y alto grado respectivamente, con una concordancia sustancial entre observadores (cirujano/anatomopatólogo; K = 0,64). No se han reportado complicaciones asociadas a la utilización de la fluoresceína ni sondas de CLE. CONCLUSIONES: La CLE representa una herramienta útil y segura, capaz de proporcionar información citológica de tumores del TUS en tiempo real que permite la identificación del grado tumoral con sustancial grado de acuerdo entre la tipificación en vivo y su análisis histopatológico final. Por este motivo, actualmente, la CLE es considerada como una herramienta en el manejo conservador del carcinoma del TUS en las guidelines de la European Association of Urology (EAU).

Endomicroscopía láser confocal en el tratamiento del tumor urotelial del tracto urinario superior / Confocal laser endomicroscopy for the treatment of upper urinary tract transitional cellcarcinoma

Objetivos: La endomicroscopía láser confocal (CLE) es una técnica óptica que permite la caracterización citológica en vivo de un tejido. Estudios previos en lesiones del tracto digestivo y respiratorio han mostrado una alta concordancia entre el resultado en vivo y el resultado histopatológico. Recientemente, se ha propuesto el uso de la CLE en el estudio del tracto urinario superior (TUS) durante la ureteroscopia, ya que permite obtener información a tiempo real del grado tumoral y complementa la información de las biopsias ureteroscópicas, que dadas sus limitaciones, pueden infraestimar el grado y el estadío de la lesión hasta en un 43% de los casos. Métodos: Se llevó a cabo una revisión de la literatura en la base de datos Pubmed/Medline siguiendo las normas Prisma. Se utilizaron 21 artículos que cumplieron los criterios de inclusión para la síntesis de la evidencia. Resultados: La sensibilidad y especificidad descrita, alcanza el 79%/78% y 67%/79% para tumores de bajo y alto grado respectivamente, con una concordancia sustancial entre observadores cirujano/anatomopatólogo; K=0,64). No se han reportado complicaciones asociadas a la utilización de la fluoresceína ni sondas de CLE. Conclusiones: La CLE representa una herramienta útil y segura, capaz de proporcionar información citológica de tumores del TUS en tiempo real que permitela identificación del grado tumoral con sustancial grado de acuerdo entre la tipificación en vivo y su análisis histopatológico final. Por este motivo, actualmente, la CLE es considerada como una herramienta en el manejo conservador del carcinoma del TUS en las guidelines de la European Association of Urology (EAU)

Objectives: Confocal lasser endomicroscopy (CLE) is an optical technique that enables in vivo cytological characterization of a tissue. Previous studies have shown it useful in the evaluation of urinary and respiratory tracts for a better characterization of mucosal lesions, showing a high concordance between in vivo and final histopathological results. Recently, the use of CLE has been proposed for the study of transitional cell carcinoma of the upper urinary tract (UUT) during ureteroscopy, because it enables real time information about tumor grade and supplements the information of ureteroscopic biopsies, which may understimate the grade and stage of the lesion up to 43% of the cases due to its limitiations. Methods: We performed a systematic review of the literature in the Pubmed/Medline database following the PRISMA standard. We selected 20 articles that complied with the inclusion criteria for evidence synthesis. Results: Equipment miniaturization has enabled CLE as part of the diagnostic options in upper urinary tract tumors. This technique performs in vivo cytological characterization of the evaluated tissue, accomplishing differentiation between tumor and normal tissue, as well as tumor grade identification. Its communicated sensitivity and specificity reach 79%/78% respectively for low grade tumors and 67%/79% for high grade, with a substantial inter observer concordance (surgeon/pathologist;k=0.64). No complications have been communicated in the literature with the use of fluorescein or confocal laser microscopy probes in patients undergoing this technique. CONCLUSIONS: CLE represents a useful and safe tool, capable of providing cytological real time information of UUT tumors that enables tumor grade identification with substantial concordance between in vivo tumor typifying and the final histopathological analysis. For this, CLE is currently considered a tool for conservative management of UUT transitional cell carcinoma in the European Association of Urology (EAU) guidelines

Adalimumab or Infliximab for the Prevention of Early Postoperative Recurrence of Crohn Disease: Results From the ENEIDA Registry.

BACKGROUND: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR. METHODS: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery. RESULTS: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR. CONCLUSIONS: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.

Quality of life during one year of postoperative prophylactic drug therapy after intestinal resection in Crohn's patients: Results of the APPRECIA trial.

BACKGROUND: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). AIMS: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. METHODS: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. RESULTS: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p ≤ 0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p < 0.001) and EQ-5D (p < 0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score (Pearson's r: -0.768) and with EQ-5D index (r: -0.644). CONCLUSION: HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapy used (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, since improvements in HRQoL were only significant in patients with endoscopic remission at 1 year.

[BCG and bladder cancer: Past, present and future.] / BCG y cáncer de vejiga: pasado, presente y futuro.

BCG has been used in the treatment of NMIBC for more than 40 years. Nevertheless, its exact working mechanisms have not been completely discovered. Clinical and basic research done over all these years has generated much information but it could be summarized in a few simple statements. It has been demonstrated the best route of administration is intravesical, BCG is superior than intracavitary chemotherapy to prevent recurrence but its adverse events are worse. Recently, it has been demonstrated that BCG could delay or prevent progression to infiltrative cancer. Nevertheless, to achieve this, maintenance therapy is necessary. Therefore, the recommendation is to treat middle and high risk cases with BCG. No significant differences in efficacy have been found between the various strains but differences in recurrence have been found between standard and reduced doses.Furthermore, the presence or absence of side effects does not seem to be a prognostic factor for the efficacy of BCG and, maintenance therapy is not associated with a significant increase in toxicity. In the future, the optimal schedule and doses must be defined, and it probably will be different for each individual. BCG shortage has led to try alternative therapies through chemo hyperthermia or electrical gradient application the efficacy of which should be evaluated. New strains and immunological treatments are also under research.

Inmunoterapia con BCG BCG y cáncer de vejiga: pasado, presente y futuro / BCG and bladder cancer: Past, present and future

Hace más de 40 años que se utiliza la BCG en el tratamiento del CVNMI. Sin embargo, los mecanismos de trabajo exactos de su funcionamiento aún no han sido totalmente descubiertos. La investigación clínica y básica realizada durante todos estos años ha generado mucha información pero que podría resumirse en unas pocas afirmaciones sencillas. Se ha demostrado que la mejor vía de administración de BCG es la vía intravesical, que la BCG es superior a la quimioterapia intracavitaria para prevenir la recurrencia pero que sus efectos adversos son peores. Recientemente se ha demostrado que BCG podría prevenir o retrasar la progresión a cáncer infiltrante. Sin embargo, para lograr esto, la terapia de mantenimiento es necesaria. Por ello, se recomienda que los tumores de riesgo intermedio y alto se traten con BCG. No se han encontrado diferencias significativas en la eficacia entre las diferentes cepas, pero si diferencia de recurrencia en la utilización de una dosis estándar frente a una reducida. Además, la presencia o ausencia de efectos secundarios no parece ser un factor pronóstico para la eficacia de BCG y la terapia de mantenimiento no se asocia con un aumento significativo de la toxicidad. En el futuro, se debe definir el esquema y la dosis óptimos, y esto probablemente sea diferente para cada individuo. La falta de suministros de BCG ha hecho que se prueben terapias alternativas mediante quimiohipertermia o aplicación de un gradiente eléctrico cuya efectividad debe ser evaluada. Nuevas cepas y tratamientos inmunológicos están también siendo investigados

BCG has been used in the treatment of NMIBC for more than 40 years. Nevertheless, its exact working mechanisms have not been completely discovered. Clinical and basic research done over all these years has generated much information but it could be summarized in a few simple statements. It has been demonstrated the best route of administration is intravesical, BCG is superior than intracavitary chemotherapy to prevent recurrence but its adverse events are worse. Recently, it has been demonstrated that BCG could delay or prevent progression to infiltrative cancer. Nevertheless, to achieve this, maintenance therapy is necessary. Therefore, the recommendation is to treat middle and high risk cases with BCG. No significant differences in efficacy have been found between the various strains but differences in recurrence have been found between standard and reduced doses. Furthermore, the presence or absence of side effects does not seem to be a prognostic factor for the efficacy of BCG and, maintenance therapy is not associated with a significant increase in toxicity. In the future, the optimal schedule and doses must be defined, and it probably will be different for each individual. BCG shortage has led to try alternative therapies through chemo hyperthermia or electrical gradient application the efficacy of which should be evaluated. New strains and immunological treatments are also under research

Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial.

BACKGROUND AND AIMS: Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. METHODS: We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. RESULTS: We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. CONCLUSIONS: ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.