Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

Adherence to endoscopic surveillance for advanced lesions and colorectal cancer in inflammatory bowel disease: an AEG and GETECCU collaborative cohort study.

BACKGROUND AND AIMS: Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence. METHODS: A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant. RESULTS: A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24-29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3-10.1; p = 0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462-5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409-7.644; p < 0.001 for intermediate- and high- vs low-risk groups). CONCLUSIONS: Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.

Re-induction With Intravenous Ustekinumab in Patients With Crohn's Disease and a Loss of Response to This Therapy.

BACKGROUND: A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn's disease who have lost the response to the treatment. METHODS: This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. RESULTS: Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. CONCLUSION: Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn's disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Infliximab in ulcerative colitis: real-life analysis of factors predicting treatment discontinuation due to lack of response or colectomy: ECIA (ACAD Colitis and Infliximab Study).

OBJECTIVE: To describe clinical practice with infliximab (IFX) in ulcerative colitis (UC); identification of predictive factors for IFX treatment discontinuation due to insufficient response and for colectomy. MATERIAL AND METHODS: Retrospective, multicentric and observational study including every UC IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological data; variables for poor prognosis; IFX prior treatments; characteristics of the IFX treatment; time from the UC diagnosis to induction with IFX; time from induction to colectomy or until data collection. Predictive and protective factors for IFX discontinuation due to lack of response and for colectomy were analyzed with binary logistic regression and Cox analysis. RESULTS: Follow-up time from induction with IFX to the collection of data or colectomy: 36.7 ± 25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX + immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%. Independent predictive or protective factors for IFX discontinuation: IMM resistance (OR: 2.9, p = 0.022, 95% CI: 1.2-7.2), prior use of leukocytapheresis (OR: 3.3, p = 0.024, 95% CI: 1.1-9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.9, and HR: 0.4, p = 0.006, 95% CI: 0.2-0.8) and corticosteroid use in induction (HR: 1.9, p = 0.049, 95% CI: 1.0-3.8). Independent predictive or protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036, 95% CI: 1.1-8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.8, and HR: 0.3, p = 0.011, 95% CI: 0.1-0.8) and severe cortico-resistant flare-up (HR: 2.5, p = 0.032, 95% CI: 1.1-5.9). CONCLUSIONS: Prior use of IMM and leukocytapheresis, the use of corticosteroids in induction and a severe cortico-resistant flare predict a worse response to IFX and the need for colectomy. Combination therapy is a protective factor for both.

Frequency, predictors, and consequences of maintenance infliximab therapy intensification in ulcerative colitis.

INTRODUCTION: Infliximab (IFX) therapy intensification in ulcerative colitis (UC) is more common than established in pivotal studies. OBJECTIVES: To establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment. METHODS: A retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX) induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy. RESULTS: Follow-up time from induction to data collection: 38 months [interquartile range (IQR), 20-62]. Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM) and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002), steroid reintroduction (35% vs. 18%; p, 0.018), and colectomy (22% vs. 6.4%; p, 0.011) were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks. CONCLUSIONS: Intensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predictsnon-intensification. Intensification, while effective, is associated with poorer outcome.

Frecuencia, factores predictores y consecuencias de la intensificación del tratamiento de mantenimiento con infliximab en la colitis ulcerosa / Frequency, predictors, and consequences of maintenance infliximab therapy intensification in ulcerative colitis

INTRODUCCIÓN: la intensificación del tratamiento con infliximab (IFX) en la colitis ulcerosa (CU) es más frecuente de lo establecido en estudios pivotales. OBJETIVOS: establecer la frecuencia y forma con la que intensificamos en CU en práctica clínica, los factores predictores y comparar la evolución entre los pacientes con tratamiento intensificado y no intensificado. MÉTODOS: estudio retrospectivo de 10 hospitales y 144 pacientes con respuesta a la inducción con IFX. Se analizaron variables predictoras de la intensificación con análisis de regresión de Cox. Se comparó la evolución, pérdida de respuesta a IFX y colectomía según tratamiento intensificado o no intensificado. RESULTADOS: tiempo de seguimiento desde la inducción hasta la recogida de datos: 38 meses [rango intercuartil (RIC) 20-62]. Tiempo de tratamiento con IFX: 24 meses (RIC, 10-44). El 37% de los pacientes requirió intensificación. Se acortó el intervalo en 36 pacientes, se aumentó la dosis en 7, ambas en 10. La introducción simultánea de inmunosupresores tiopurínicos (INM) e IFX predijo la intensificación de forma independiente [Hazard ratio (HR) 0,034 p 0,006 IC 0,003-0,371]. En los pacientes con tratamiento intensificado fue más frecuente la suspensión de IFX por pérdida de respuesta (30,4% vs. 10,2% p 0,002), la reintroducción de corticoides (35% vs. 18%, p 0,018) y la colectomía (22% vs. 6,4% p 0,011). El 17% de los pacientes intensificados volvió a recibir 5 mg/kg cada 8 semanas. CONCLUSIONES: la intensificación es frecuente y en ocasiones reversible. La introducción del INM en el momento de la inducción con IFX predice la no intensificación. La intensificación, aunque eficaz, se asocia a una peor evolución

INTRODUCTION: Infliximab (IFX) therapy intensification in ulcerative colitis (UC) is more common than established in pivotal studies. OBJECTIVES: To establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment. METHODS: A retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX) induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy. RESULTS: Follow-up time from induction to data collection: 38 months [interquartile range (IQR), 20-62]. Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM) and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002), steroid reintroduction (35% vs. 18%; p, 0.018), and colectomy (22% vs. 6.4%; p, 0.011) were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks. CONCLUSIONS: Intensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predicts non-intensification. Intensification, while effective, is associated with poorer outcome